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Publications (10 of 23) Show all publications
Kinch, A., Hallböök, H., Arvidson, J., Sällström, K., Bondeson, K. & Pauksen, K. (2018). Long-term outcome of Epstein-Barr virus DNAemia and PTLD with the use of preemptive rituximab following allogeneic HSCT. Leukemia and Lymphoma, 59(5), 1172-1179
Open this publication in new window or tab >>Long-term outcome of Epstein-Barr virus DNAemia and PTLD with the use of preemptive rituximab following allogeneic HSCT
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2018 (English)In: Leukemia and Lymphoma, ISSN 1042-8194, E-ISSN 1029-2403, Vol. 59, no 5, p. 1172-1179Article in journal (Refereed) Published
Abstract [en]

We studied retrospectively the outcome of Epstein-Barr virus (EBV)-related disease with EBV monitoring and preemptive rituximab to prevent post-transplant lymphoproliferative disorder (PTLD) in 319 consecutive allogeneic stem cell transplantations 2004-2012. Patients who received anti-thymocyte globulin (ATG) or alemtuzumab were regarded as high-risk for PTLD (n = 214). EBV DNAemia ≥1000 copies/mL plasma was observed in 50 (23%) of the high-risk patients. Thirty-three of the high-risk (15%) and one of the low-risk (1%) patients received rituximab, in combination with reduction of immunosuppression (n = 24) or chemotherapy (n = 4). Although rituximab was initiated only 5 d after first EBV load ≥1000 copies/mL, 85% of the rituximab-treated patients developed symptoms (lymphadenopathy 50%, fever 76%, and encephalitis/meningitis 12%). Response-rate to EBV treatment was 88%. Overall survival at 1- and 5-year was 71 and 52% for rituximab-treated patients, which was not inferior to all other patients post-transplant. In conclusion, rituximab therapy for EBV DNAemia does not affect long-term survival negatively.

Keyword
EBV, PTLD, allogeneic HSCT, rituximab, survival
National Category
Clinical Medicine
Identifiers
urn:nbn:se:uu:diva-343169 (URN)10.1080/10428194.2017.1365860 (DOI)000426933700017 ()28831836 (PubMedID)
Available from: 2018-02-26 Created: 2018-02-26 Last updated: 2018-05-16Bibliographically approved
Bergqvist, A., Bondeson, K., Öhrmalm, C., Strand, M., Lysvand, H., Teppor, M., . . . Kainov, D. (2018). Novel activities of safe-in-human broad-spectrum antiviral agents.. Antiviral Research, Article ID S0166-3542(18)30098-6.
Open this publication in new window or tab >>Novel activities of safe-in-human broad-spectrum antiviral agents.
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2018 (English)In: Antiviral Research, ISSN 0166-3542, E-ISSN 1872-9096, article id S0166-3542(18)30098-6Article in journal (Refereed) Epub ahead of print
Abstract [en]

According to the WHO, there is an urgent need for better control of viral diseases. Re-positioning existing safe-in-human antiviral agents from one viral disease to another could play a pivotal role in this process. Here, we reviewed all approved, investigational and experimental antiviral agents, which are safe in man, and identified 59 compounds that target at least three viral diseases. We tested 55 of these compounds against eight different RNA and DNA viruses. We found novel activities for dalbavancin against echovirus 1, ezetimibe against human immunodeficiency virus 1 and Zika virus, as well as azacitidine, cyclosporine, minocycline, oritavancin and ritonavir against Rift valley fever virus. Thus, the spectrum of antiviral activities of existing antiviral agents could be expanded towards other viral diseases.

National Category
Microbiology in the medical area
Identifiers
urn:nbn:se:uu:diva-350000 (URN)10.1016/j.antiviral.2018.04.016 (DOI)29698664 (PubMedID)
Available from: 2018-05-02 Created: 2018-05-02 Last updated: 2018-05-07
Thörn, M., Rorsman, F., Rönnblom, A., Sangfelt, P., Wanders, A., Eriksson, B.-M. & Bondeson, K. (2016). Active cytomegalovirus infection diagnosed by real-time PCR in patients with inflammatory bowel disease: a prospective, controlled observational study. Scandinavian Journal of Gastroenterology, 51(9), 1075-1080
Open this publication in new window or tab >>Active cytomegalovirus infection diagnosed by real-time PCR in patients with inflammatory bowel disease: a prospective, controlled observational study
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2016 (English)In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 51, no 9, p. 1075-1080Article in journal (Refereed) Published
Abstract [en]

Objective: It is assumed that cytomegaloviral (CMV) infection in inflammatory bowel disease (IBD) is caused by reactivation due to the immunosuppressive therapy, but the role of CMV as a pathophysiological factor and prognostic marker in IBD is unclear. The aim of this study was to investigate CMV infection in IBD, with real-time polymerase chain reaction (PCR) and immunohistochemistry, with emphasis on newly diagnosed disease.

Materials and methods: In this prospective, controlled study, 67 patients with IBD and 34 control patients with irritable bowel syndrome (IBS) or rectal bleeding were included. Serology for CMV was analysed along with CMV DNA in plasma, mucosal biopsies, and faeces. Mucosal biopsies were further analysed with histopathology and CMV immunohistochemistry.

Results: Detection of CMV IgM was more common in patients with IBD, compared to controls, 21% versus 3%. CMV DNA was found in 16% of patients with newly diagnosed, untreated IBD and in 38% of steroid-treated patients. Four of the five patients that needed urgent surgery were CMV-DNA positive in at least one of three sample types. None of the controls had detectable CMV DNA.

Conclusions: Active CMV infection was found in high proportions of newly diagnosed untreated patients with IBD, in patients on immunosuppression and in patients in the need of surgery. Low CMV-DNA levels in non-immunosuppressed patients were not a risk factor for the development of more severe IBD, while the detection of CMV DNA in patients on immunosuppressive therapy may foresee disease progression.

National Category
Infectious Medicine
Identifiers
urn:nbn:se:uu:diva-301631 (URN)10.3109/00365521.2016.1156154 (DOI)000381406800010 ()27142339 (PubMedID)
Funder
Swedish Society of Medicine
Available from: 2016-08-23 Created: 2016-08-23 Last updated: 2018-05-18Bibliographically approved
Assadian, F., Sandström, K., Bondeson, K., Laurell, G., Lidian, A., Svensson, C., . . . Punga, T. (2016). Distribution and Molecular Characterization of Human Adenovirus and Epstein-Barr Virus Infections in Tonsillar Lymphocytes Isolated from Patients Diagnosed with Tonsillar Diseases. PLoS ONE, 11(5), Article ID e0154814.
Open this publication in new window or tab >>Distribution and Molecular Characterization of Human Adenovirus and Epstein-Barr Virus Infections in Tonsillar Lymphocytes Isolated from Patients Diagnosed with Tonsillar Diseases
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2016 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, no 5, article id e0154814Article in journal (Refereed) Published
Abstract [en]

Surgically removed palatine tonsils provide a conveniently accessible source of T and B lymphocytes to study the interplay between foreign pathogens and the host immune system. In this study we have characterised the distribution of human adenovirus (HAdV), Epstein-Barr virus (EBV) and human cytomegalovirus (HCMV) in purified tonsillar T and B cell-enriched fractions isolated from three patient age groups diagnosed with tonsillar hypertrophy and chronic/recurrent tonsillitis. HAdV DNA was detected in 93 out of 111 patients (84%), while EBV DNA was detected in 58 patients (52%). The most abundant adenovirus type was HAdV-5 (68%). None of the patients were positive for HCMV. Furthermore, 43 patients (39%) showed a co-infection of HAdV and EBV. The majority of young patients diagnosed with tonsillar hypertrophy were positive for HAdV, whereas all adult patients diagnosed with chronic/recurrent tonsillitis were positive for either HAdV or EBV. Most of the tonsils from patients diagnosed with either tonsillar hypertrophy or chronic/recurrent tonsillitis showed a higher HAdV DNA copy number in T compared to B cell-enriched fraction. Interestingly, in the majority of the tonsils from patients with chronic/recurrent tonsillitis HAdV DNA was detected in T cells only, whereas hypertrophic tonsils demonstrated HAdV DNA in both T and B cell-enriched fractions. In contrast, the majority of EBV positive tonsils revealed a preference for EBV DNA accumulation in the B cell-enriched fraction compared to T cell fraction irrespective of the patients' age.

National Category
Surgery Otorhinolaryngology Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-297795 (URN)10.1371/journal.pone.0154814 (DOI)000375674800050 ()27136093 (PubMedID)
Funder
Swedish Cancer Society, 12 0504Swedish Cancer Society, 13 0469Swedish Research Council, K2012-99X-21959-01-3Swedish Research Council, 2006-5038-36531-16Åke Wiberg Foundation
Note

De 2 sista författarna delar sistaförfattarskapet.

Available from: 2016-06-28 Created: 2016-06-28 Last updated: 2017-11-28Bibliographically approved
Gullsby, K. & Bondeson, K. (2016). No detection of macrolide-resistant Mycoplasma pneumoniae from Swedish patients, 1996-2013.. Infection Ecology & Epidemiology, 6(1), Article ID 31374.
Open this publication in new window or tab >>No detection of macrolide-resistant Mycoplasma pneumoniae from Swedish patients, 1996-2013.
2016 (English)In: Infection Ecology & Epidemiology, ISSN 2000-8686, E-ISSN 2000-8686, Infection ecology & epidemiology, Vol. 6, no 1, article id 31374Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Mycoplasma pneumoniae is a common cause of respiratory infections which can cause life-threatening pneumonia and serious extrapulmonary manifestations. Since the year 2000, the emergence of macrolide-resistant M. pneumoniae strains has increased with varying incidences across countries. In China more than 90% of the strains are resistant. M. pneumoniae diagnostics is mostly done with molecular methods, and in Sweden antibiotic resistance surveillance is not routinely performed. The prevalence of macrolide-resistant M. pneumoniae has not previously been studied in Sweden.

MATERIAL AND METHODS: A total of 563 M. pneumoniae-positive respiratory samples, collected from four counties in Sweden between 1996 and 2013, were screened for mutations associated with macrolide resistance using a duplex FRET real-time PCR method. The real-time PCR targets the 23S rRNA gene, and differentiation between wild-type and resistant strains was achieved with a melting curve analysis.

RESULTS: Of the 563 samples included, 548 were analyzed for mutations associated with macrolide resistance. No mutations were found. The detection rate of macrolide-resistant M. pneumoniae in this study was 0% [0.00-0.84%].

CONCLUSION: No macrolide-resistant M. pneumoniae has been detected in Sweden. However, the emergence and spread of macrolide-resistant M. pneumoniae strains in many countries commands continuous epidemiological surveillance.

Keyword
Mycoplasma pneumoniae, antibiotic resistance, diagnostics, macrolide, treatment
National Category
Infectious Medicine
Identifiers
urn:nbn:se:uu:diva-319205 (URN)10.3402/iee.v6.31374 (DOI)27258207 (PubMedID)
Available from: 2017-03-31 Created: 2017-03-31 Last updated: 2017-05-18Bibliographically approved
Lindström, I., Palanisamy, N., Kjellin, M., Danielsson, A., Bondeson, K. & Lennerstrand, J. (2013). Implications of baseline polymorphisms for potential resistance to NS3 protease and NS5A inhibitors in hepatitis C virus genotypes 1a, 2b and 3a. Paper presented at International Workshop on HIV and Hepatitis Virus Drug Resistance and Curative Strategies, JUN 04-08, 2013, Toronto, CANADA. Antiviral Therapy, 18(S1), A55-A55
Open this publication in new window or tab >>Implications of baseline polymorphisms for potential resistance to NS3 protease and NS5A inhibitors in hepatitis C virus genotypes 1a, 2b and 3a
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2013 (English)In: Antiviral Therapy, ISSN 1359-6535, E-ISSN 2040-2058, Vol. 18, no S1, p. A55-A55Article in journal, Meeting abstract (Other academic) Published
National Category
Infectious Medicine Pharmacology and Toxicology
Identifiers
urn:nbn:se:uu:diva-228255 (URN)000335229500049 ()
Conference
International Workshop on HIV and Hepatitis Virus Drug Resistance and Curative Strategies, JUN 04-08, 2013, Toronto, CANADA
Available from: 2014-07-08 Created: 2014-07-08 Last updated: 2018-01-11Bibliographically approved
Palanisamy, N., Danielsson, A., Kokkula, C., Yin, H., Bondeson, K., Wesslen, L., . . . Lennerstrand, J. (2013). Implications of baseline polymorphisms for potential resistance to NS3 protease inhibitors in Hepatitis C virus genotypes 1a, 2b and 3a. Antiviral Research, 99(1), 12-17
Open this publication in new window or tab >>Implications of baseline polymorphisms for potential resistance to NS3 protease inhibitors in Hepatitis C virus genotypes 1a, 2b and 3a
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2013 (English)In: Antiviral Research, ISSN 0166-3542, E-ISSN 1872-9096, Vol. 99, no 1, p. 12-17Article in journal (Refereed) Published
Abstract [en]

The future interferon-free treatment of hepatitis C virus (HCV) infection could include NS3 protease inhibitors (PIs) for potent pan-genotypic effect. We studied the prevalence of pre-existing PI resistance associated amino acid variants (RAVs) in 126 treatment-naive patient samples of HCV genotypes 1a, 2b and 3a, the most common genotypes in Sweden. The NS3 genes were each amplified by nested PCR method with degenerated primers to enable a broad genotype analysis. Population sequencing method was used, and the sequences were aligned with the NS3 sequence from HCV genotype 1a H77 strain. Interpretation of fold-change resistance to NS3 candidate drugs were done from already published phenotypic resistance data. The prevalence of known PI RAVs at baseline in genotype 1a was 28% (15/53), either single (V36L or Q80K/R) or combinations (T54A/S and V55A/I) of mutation(s). In genotype 2b, specific mutations like V36L, Q80G and S122R of viral NS3 protease gene were found in 100% (11/11). These may be the natural polymorphisms unique to genotype 2b. Similarly, specific mutations like V36L and D168Q were found uniquely in all 3a samples (30/30). The natural PI RAVs found in genotype 1a, although with relatively weak resistance, could still render up to 10-fold-resistance to the approved (boceprevir and telaprevir) and the 2nd generation Pis (faldaprevir and simeprevir). Moreover, the natural polymorphisms in genotype 2b (i.e. S122R) and 3a (i.e. D168Q), with inherent PI drug resistance of up to 20 and 700 fold respectively, would explain why current Pis are primarily directed against genotype 1.

Keyword
Hepatitis C virus, NS3 protease inhibitors, Resistance, Resistance associated amino acid variants (RAVs), Prevalence
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-204259 (URN)10.1016/j.antiviral.2013.04.018 (DOI)000320906600003 ()
Available from: 2013-07-30 Created: 2013-07-29 Last updated: 2017-12-06Bibliographically approved
Öhrmalm, C., Eriksson, R., Jobs, M., Simonson, M., Strømme, M., Bondeson, K., . . . Blomberg, J. (2012). Variation-tolerant capture and multiplex detection of nucleic acids: application to detection of microbes. Journal of Clinical Microbiology, 50(10), 3208-3215
Open this publication in new window or tab >>Variation-tolerant capture and multiplex detection of nucleic acids: application to detection of microbes
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2012 (English)In: Journal of Clinical Microbiology, ISSN 0095-1137, E-ISSN 1098-660X, Vol. 50, no 10, p. 3208-3215Article in journal (Refereed) Published
Abstract [en]

In contrast to ordinary PCRs, which have a limited multiplex capacity and often return false-negative results due to target variation or inhibition, our new detection strategy, VOCMA (variation-tolerant capture multiplex assay), allows variation-tolerant, target-specific capture and detection of many nucleic acids in one test. Here we demonstrate the use of a single-tube, dual-step amplification strategy that overcomes the usual limitations of PCR multiplexing, allowing at least a 22-plex format with retained sensitivity. Variation tolerance was achieved using long primers and probes designed to withstand variation at known sites and a judicious mix of degeneration and universal bases. We tested VOCMA in situations where enrichment from a large sample volume with high sensitivity and multiplexity is important (sepsis; streptococci, enterococci, and staphylococci, several enterobacteria, candida, and the most important antibiotic resistance genes) and where variation tolerance and high multiplexity is important (gastroenteritis; astrovirus, adenovirus, rotavirus, norovirus genogroups I and II, and sapovirus, as well as enteroviruses, which are not associated with gastroenteritis). Detection sensitivities of 10 to 1,000 copies per reaction were achieved for many targets. VOCMA is a highly multiplex, variation-tolerant, general purpose nucleic acid detection concept. It is a specific and sensitive method for simultaneous detection of nucleic acids from viruses, bacteria, fungi, and protozoa, as well as host nucleic acid, in the same test. It can be run on an ordinary PCR and a Luminex machine and is suitable for both clinical diagnoses and microbial surveillance.

National Category
Nano Technology Medical and Health Sciences
Research subject
Engineering Science with specialization in Nanotechnology and Functional Materials; Engineering Science with specialization in Electronics
Identifiers
urn:nbn:se:uu:diva-181809 (URN)10.1128/JCM.06382-11 (DOI)000308870200010 ()22814465 (PubMedID)
Available from: 2012-10-01 Created: 2012-10-01 Last updated: 2017-12-07Bibliographically approved
Yin, H., Lennerstrand, J. & Bondeson, K. (2009). Determination of Hepatitis C (HCV) Genotypes and Drug Resistances By a Efficient and Cost-effective Sequence Analysis Method: One cDNA synthesis, two assays. In: : . Paper presented at World Summit of Antivirals 2009; July 18-20, 2009; Beijing, China.
Open this publication in new window or tab >>Determination of Hepatitis C (HCV) Genotypes and Drug Resistances By a Efficient and Cost-effective Sequence Analysis Method: One cDNA synthesis, two assays
2009 (English)Conference paper, Published paper (Refereed)
Abstract [en]

A more efficient, high specific and cost-effective RT-PCR sequencing method has developed for a correct HCV genotype and study the natural genetic variability and drug resistance within HCV non-structure region.

Infection with hepatitis C virus (HCV) frequently leads to chronic hepatitis with an increased risk for the development of liver cirrhosis and liver cancer. HCV is classified into eleven major (designated 1-11), many subtypes (designated a, b, c, etc.), and about 100 different strains based on the sequence heterogeneity. In Sweden, the genotype distribution was different from that in studies from other parts of the world, with a lower frequency of genotype 1b and a higher frequency of genotype 1a and 3a.

HCVgenotype differences affect responses to antiviral therapy, for exemple, patient infected with genotype 1 responds only 50% to PEG-IFN-á and ribavirin treatment in 48 weeks and approximately 80% of patients infected with HCV genotypes 2 and 3 treated with PEG-IFN-á plus ribavirin in 24 weeks achieve a sustained virological response. It has been suggest that the therapeutic strategy should be different for genotype 1 (and 4-6) and genotypes 2 and 3, respectively. Therefore, determination of HCV genotype and antiviral resistance are important and must be performed after the diagnosis of chronic hepatitis C, in order to provide the most effective treatment for HCV infected patients.

To identify a correct genotypes and mutations that confer drug resistance to HCV protease inhibitors in untreated patients, especially mutations involving R155K substitution. We have recently developed a "One cDNA synthesis and two assays" RT-nestPCR method where we sequenced the HCV NS5b region for the genotyping and protease gene for determination of resistance mutations. cDNA was synthesis using random primer and PCR primers were designed from the NS5b region for genotyping and NS3 regions for determining mutations which covers known 10 protease resistance in NS3, including R155K and V36M. Sequences were then analyzed and phylogenetic tree was made for genotypes according to alignment, and identification of resistance substitutions in the NS3 protease was performed by Seqscape software. RT-nestPCR assay was successful in samples containing >100IU/mL HCV RNA. The accuracy of this method has been validated by QCMD (Quality Control for Molecular Diagnosis, UK). Our method represents a more efficient in identifying mixture of genotypes (2k/1b, 2a/2c/2i), specific and reliable method for differentiation between all genotypes and subtypes, economic and is useful in study natural genetic, mutations and polymorphism within HCV NS3 protease region.

This simple, more efficient, specific, low-cost and reproducible method can be used as a routine diagnostic and should also be useful to monitor resistance directly during treatment. The results will be integrated in discussions of therapeutic and diagnostic strategies in the Nordic regions. Such diagnostic method has yet been developed in Sweden.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-112042 (URN)
Conference
World Summit of Antivirals 2009; July 18-20, 2009; Beijing, China
Available from: 2010-01-07 Created: 2010-01-07 Last updated: 2013-10-24Bibliographically approved
Lennerstrand, J., Bondeson, K., Bergqvist, A., Blomberg, J. & Öberg, B. (2009). Nya antivirala läkemedel mot hepatit C i kliniska studier: Ger hopp om bot - men resistens-problematiken måste bemästras. Läkartidningen, 106(48), 3254-3260
Open this publication in new window or tab >>Nya antivirala läkemedel mot hepatit C i kliniska studier: Ger hopp om bot - men resistens-problematiken måste bemästras
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2009 (Swedish)In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 106, no 48, p. 3254-3260Article in journal (Refereed) Published
National Category
Medical and Health Sciences
Research subject
Clinical Virology
Identifiers
urn:nbn:se:uu:diva-132436 (URN)20101837 (PubMedID)
Note

English title: "New antiviral agents against hepatitis C in clinical trials. Hope for a cure--but resistance problems must be overcome"

Available from: 2010-10-20 Created: 2010-10-20 Last updated: 2017-12-12Bibliographically approved
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Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0001-9684-7887

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