Lennart Svensson

Linköping University, Linköping, OEstergoetland, Sweden

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Publications (100)433.81 Total impact

  • Article: Susceptibility of children to sapovirus infections, nicaragua, 2005-2006.
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    ABSTRACT: We describe the genetic diversity of sapovirus (SaV) in children in Nicaragua and investigate the role of host genetic factors and susceptibility to SaV infections. Our results indicate that neither ABO blood group, Lewis phenotype, nor secretor status affects susceptibility to SaV infection in Nicaragua.
    Emerging Infectious Diseases 11/2012; 18(11):1875-8. · 6.79 Impact Factor
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    Article: Norovirus GII.4 Virus-like Particles Recognize Galactosylceramides in Domains of Planar Supported Lipid Bilayers.
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    ABSTRACT: A sticky situation: Domain-dependent recognition of the glycosphingolipid galactosylceramide by norovirus-like particles (see picture; red/yellow) is shown using supported lipid bilayers (purple) as model membranes. Optimal ligand presentation is found to promote strong binding to GalCer. This presentation can be found at the edges of the glycosphingolipid-enriched domains (green) and binding is repressed in the absence of these domains.
    Angewandte Chemie International Edition 10/2012; · 13.45 Impact Factor
  • Article: Rotavirus in diarrheal children in rural Burkina Faso: High prevalence of genotype G6P[6].
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    ABSTRACT: Group A rotavirus (RVA) is the most common cause of severe gastroenteritis in young children globally, and responsible for a significant number of deaths in African countries. While vaccines are available, trials have shown a lesser efficacy in Africa. One of the reasons could be the prevalence and/or emergence of unusual or novel RVA strains, as many strains detected in African countries remain uncharacterized. In this study, we characterized RVA positive specimens from two remote rural areas in Burkina Faso, West Africa. In total 56 RVA positive specimens were subgrouped by their VP6 gene, and G-and P typed by PCR and/or sequencing of the VP7 and VP4 genes, respectively. Notably, we found a high prevalence of the unusual G6P[6]SGI strains (23%). It was the second most common constellation after G9P[8]SGII (32%); and followed by G1P[8]SGII (20%) and G2P[4]SGI (9%). We also detected a G8P[6]SGI strain, for the first time in Burkina Faso. The intra-genetic diversity was high for the VP4 gene with two subclusters within the P[8] genotype and three subclusters within the P[6] genotype which were each associated with a specific G-type, thereby suggesting a genetic linkage. The G6P[6]SGI and other SGI RVA strains infected younger children as compared to SGII strains (p<0.05). To conclude, in this study we observed the emergence of unusual RVA strains and high genetic diversity of RVA in remote rural areas of Burkina Faso. The results highlight the complexity of RVA epidemiology which may have implication for the introduction of rotavirus vaccines currently being evaluated in many African countries.
    Infection, genetics and evolution: journal of molecular epidemiology and evolutionary genetics in infectious diseases 09/2012; 12(8):1892-1898. · 3.22 Impact Factor
  • Article: Molecular epidemiology of rotavirus and norovirus in Ile-Ife, Nigeria: high prevalence of G12P[8] rotavirus strains and detection of a rare norovirus genotype.
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    ABSTRACT: Rotavirus (RV) and norovirus (NoV) are considered the most common causes of viral gastroenteritis in children. In this study, the prevalence of RV and NoV infection in 55 children with diarrhea from the rural community Akinlalu in Southwestern Nigeria was investigated using real-time PCR assays. The RV and NoV strains were genotyped by PCR and/or sequencing. RV and NoV infections occurred with a prevalence of 34.5% and 25.5% respectively, with predominance in children <1 year. Most infections occurred during the dry season with increasing prevalence of RV as the dry season progressed (October-January). Infections with RV VP6 subgroup (SG) II were more prevalent (27.3%) than SGI (7.3%). Similarly, NoV genogroup II infections were more common (23.6%) than genogroup I (1.8%). Five children out of 55 (9.1%) were co-infected with both RV and NoV. Notably, G12P[8] was the predominant RV strain (36.8%, n = 7), observed for the first time in Nigeria. The VP7 gene of the G12 strains clustered within lineage III, sharing high nucleotide identity with each other (>99%) indicating introduction in Nigeria from a single donor. Furthermore, a putative novel genotype within genogroup I NoV was detected, which till date has only been reported once in humans. To conclude, a high prevalence of the emerging G12P[8] RV strain was observed for the first time in Nigeria, as well as a putative novel NoV genotype in humans. These results provide new information which can be important for future vaccine evaluations and possible introduction in Nigeria.
    Journal of Medical Virology 09/2012; 84(9):1489-96. · 2.82 Impact Factor
  • Article: Towards a human rotavirus disease model.
    Marie Hagbom, Sumit Sharma, Ove Lundgren, Lennart Svensson
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    ABSTRACT: While the clinical importance of human rotavirus (RV) disease is well recognized and potent vaccines have been developed, our understanding of how human RV causes diarrhoea, vomiting and death remains unresolved. The fact that oral rehydration corrects electrolyte and water loss, indicates that enterocytes in the small intestine have a functional sodium-glucose co-transporter. Moreover, RV infection delays gastric emptying and loperamide appears to attenuate RV diarrhoea, thereby suggesting activation of the enteric nervous system. Serotonin (5-HT) receptor antagonists attenuate vomiting in young children with gastroenteritis while zinc and enkephalinase inhibitors attenuate RV-induced diarrhoea. In this review we discuss clinical symptoms, pathology, histology and treatment practices for human RV infections and compile the data into a simplified disease model.
    Current opinion in virology. 06/2012; 2(4):408-18.
  • Article: Vaccine-derived NSP2 segment in rotaviruses from vaccinated children with gastroenteritis in Nicaragua.
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    ABSTRACT: Rotavirus (RV) vaccination programs have been established in several countries using the human-attenuated G1P[8] monovalent vaccine Rotarix (GlaxoSmithKline) and/or the human-bovine reassortant G1, G2, G3, G4, P[8] pentavalent vaccine RotaTeq (Merck). The efficacy of both vaccines is high (∼90%) in developed countries, but can be remarkably lower in developing countries. For example, a vaccine efficacy against severe diarrhea of only 58% was observed in a 2007-2009 Nicaraguan study using RotaTeq. To gain insight into the significant level of vaccine failure in this country, we sequenced the genomes of RVs recovered from vaccinated Nicaraguan children with gastroenteritis. The results revealed that all had genotype specificities typical for human RVs (11 G1P[8], 1 G3P[8]) and that the sequences and antigenic epitopes of the outer capsid proteins (VP4 and VP7) of these viruses were similar to those reported for RVs isolated elsewhere in the world. As expected, nine of the G1P[8] viruses and the single G3P[8] virus had genome constellations typical of human G1P[8] and G3P[8] RVs: G1/3-P[8]-I1-R1-C1-M1-A1-N1-T1-E1-H1. However, two of the G1P[8] viruses had atypical constellations, G1-P[8]-I1-R1-C1-M1-A1-N2-T1-E1-H1, due to the presence of a genotype-2 NSP2 (N2) gene. The sequence of the N2 NSP2 gene was identical to the bovine N2 NSP2 gene of RotaTeq, indicating that the two atypical viruses originated via reassortment of human G1P[8] RVs with RotaTeq viruses. Together, our data suggest that the high level of vaccine failure in Nicaraguan is probably not due to antigenic drift of commonly circulating virus strains nor the emergence of new antigenetically distinct virus strains. Furthermore, our data suggest that the widespread use of the RotaTeq vaccine has led to the introduction of vaccine genes into circulating human RVs.
    Infection, genetics and evolution: journal of molecular epidemiology and evolutionary genetics in infectious diseases 04/2012; 12(6):1282-94. · 3.22 Impact Factor
  • Article: Emergence of unusual G6P[6] rotaviruses in children, Burkina Faso, 2009-2010.
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    ABSTRACT: To obtain more information about rotavirus (ROTAV) genotypes in Burkina Faso, we characterized 100 ROTAVs isolated from fecal samples of children with acute gastroenteritis in the capital city of Ouagadougou, during December 2009-March 2010. Of note, 13% of the ROTAV-positive samples, including those with mixed infections, were positive for the unusual G6 genotype ROTAV strain. The genotypes identified were G9P[8], G6P[6], G1P[6], G3P[6], G1P[8], and G2P[4]. G9P[8] subgroup (SG)II strains dominated during the beginning of the ROTAV season, but later in the season, other G types associated with P[6] and SGI specificity emerged. This emergence was related to a shift in the overall age of infected children; ROTAV SGII infected younger children and induced more severe symptoms. The finding of a high incidence of G6P[6] strains highlights the need for long-term surveillance of ROTAV strains in Burkina Faso, especially when ROTAV vaccination is being considered in several African countries.
    Emerging Infectious Diseases 04/2012; 18(4):589-97. · 6.79 Impact Factor
  • Article: Aichi virus infection in elderly people in Sweden.
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    ABSTRACT: Aichi virus (AiV), genus Kobuvirus, family Picornaviridae, is associated with gastroenteritis in humans. Previous studies have shown high seroprevalence but low incidence (0.9-4.1%) in clinical samples. We report here the first detection of AiV in Sweden. Two hundred twenty-one specimens from hospitalized patients with diarrhea, who were negative for other enteric viruses, were included in the study. AiV were detected in three specimens, all from elderly patients. Phylogenetic analysis revealed that the three Swedish isolates belonged to genotype A and were genetically closest to European and Asian strains of AiV.
    Archives of Virology 03/2012; 157(7):1365-9. · 2.11 Impact Factor
  • Article: Susceptibility to winter vomiting disease: a sweet matter.
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    ABSTRACT: Norovirus, the cause of winter vomiting disease, has emerged in recent years to be a major cause of sporadic and epidemic gastroenteritis worldwide. The virus has been estimated to cause >200,000 deaths each year in developing countries. Although the virus is highly contagious, volunteer and field studies have shown that a subset of individuals appears resistant to infections. A single nucleotide mutation (G428A) in the fucosyltransferase gene (FUT2) on chromosome 19 provides strong protection from infection in 20% of the white population. Histo-blood group ABO(H) antigens with terminal fucose are believed to function as receptors for human norovirus in the gastrointestinal tract, but also negatively charged potential receptors have been identified. Norovirus infection is a unique example where a single nucleotide mutation in a fucosyltransferase gene plays a crucial role in susceptibility to one of the most common viral diseases. This review discusses the role of host genetics and carbohydrate structures in susceptibility to winter vomiting disease.
    Reviews in Medical Virology 11/2011; 21(6):370-82. · 7.20 Impact Factor
  • Article: Burden of rotavirus and other enteropathogens among children with diarrhea in Burkina Faso.
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    ABSTRACT: There is limited information available regarding the etiology of gastrointestinal infections in Burkina Faso. The aim of this study was to investigate the prevalence and epidemiology of enteric pathogens causing gastroenteritis in young children, with a focus on rotavirus, and to investigate the levels of malnutrition and other clinical factors in association with the severity of diarrhea. A prospective study was undertaken from May 2009 to March 2010, covering the rainy and dry seasons, at the Saint Camille Medical Center in Ouagadougou, Burkina Faso. A total of 309 children less than 5 years of age with diarrhea were enrolled and examined for rotavirus, bacterial, and parasitic infections, as well as clinico-epidemiological aspects. At least one enteropathogen was detected in 57.9% (n=179) of the children. Of these, 32.4% had rotavirus infections, 16.8% bacterial infections (enteropathogenic Escherichia coli 9.7%, Shigella spp 5.8%, and Salmonella spp 2.3%), and 18.8% parasitic infections (Giardia lamblia 11.3%, Trichomonas intestinalis 6.8%, Entamoeba histolytica/dispar 1.3%). During the cold dry period from December 2009 to February 2010, we observed a large increase in diarrhea cases, which was mainly attributed to rotavirus infections, as 63.8% of these diarrhea cases were positive for rotavirus. In contrast, no rotavirus infection was observed during the rainy season (June-September 2009), when the frequency of parasitic infections was high. Rotavirus and parasitic infections were age-related, with rotavirus being more prevalent in young children (<12 months) and parasites more common in older children (>12 months), while bacteria were equally prevalent among all age groups. Rotavirus infections exhibited more severe symptoms compared to bacteria and parasites, and were associated with fever, vomiting, and severe dehydration. Malnutrition, especially acute malnutrition (wasting), was significantly associated with more severe symptoms in rotavirus-induced diarrhea. The undernourished children also exhibited a prolonged duration of diarrheal episodes. This study demonstrates rotavirus as the main etiological agent in pediatric diarrhea in Burkina Faso, and further shows the great severity of rotavirus-induced diarrhea in undernourished children in Burkina Faso.
    International journal of infectious diseases: IJID: official publication of the International Society for Infectious Diseases 09/2011; 15(9):e646-52. · 2.17 Impact Factor
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    Article: Rotavirus stimulates release of serotonin (5-HT) from human enterochromaffin cells and activates brain structures involved in nausea and vomiting.
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    ABSTRACT: Rotavirus (RV) is the major cause of severe gastroenteritis in young children. A virus-encoded enterotoxin, NSP4 is proposed to play a major role in causing RV diarrhoea but how RV can induce emesis, a hallmark of the illness, remains unresolved. In this study we have addressed the hypothesis that RV-induced secretion of serotonin (5-hydroxytryptamine, 5-HT) by enterochromaffin (EC) cells plays a key role in the emetic reflex during RV infection resulting in activation of vagal afferent nerves connected to nucleus of the solitary tract (NTS) and area postrema in the brain stem, structures associated with nausea and vomiting. Our experiments revealed that RV can infect and replicate in human EC tumor cells ex vivo and in vitro and are localized to both EC cells and infected enterocytes in the close vicinity of EC cells in the jejunum of infected mice. Purified NSP4, but not purified virus particles, evoked release of 5-HT within 60 minutes and increased the intracellular Ca²⁺ concentration in a human midgut carcinoid EC cell line (GOT1) and ex vivo in human primary carcinoid EC cells concomitant with the release of 5-HT. Furthermore, NSP4 stimulated a modest production of inositol 1,4,5-triphosphate (IP₃), but not of cAMP. RV infection in mice induced Fos expression in the NTS, as seen in animals which vomit after administration of chemotherapeutic drugs. The demonstration that RV can stimulate EC cells leads us to propose that RV disease includes participation of 5-HT, EC cells, the enteric nervous system and activation of vagal afferent nerves to brain structures associated with nausea and vomiting. This hypothesis is supported by treating vomiting in children with acute gastroenteritis with 5-HT₃ receptor antagonists.
    PLoS Pathogens 07/2011; 7(7):e1002115. · 9.13 Impact Factor
  • Article: Prefrontal NMDA receptor antagonism reduces impairments in pre-attentive information processing.
    Daniel Klamer, Lennart Svensson, Kim Fejgin, Erik Pålsson
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    ABSTRACT: A well established theory proposes that glutamate signalling via the NMDA receptor is compromised in patients with schizophrenia. Deficits related to NMDA receptor signalling can be observed in several brain regions including the prefrontal cortex (PFC), an area extensively linked to the cognitive dysfunction in this disease and notably affected by NMDA receptor antagonists such as phencyclidine (PCP). In addition, a number of studies suggest that normalizing of PFC function could constitute a treatment rationale for schizophrenia. To further study the role of PFC function we investigated the effect of local PFC NMDA receptor blockade on impaired prepulse inhibition (PPI) induced by systemic administration of PCP. Mice received prefrontal injections of PCP (0.01, 0.1 or 1mM) before PCP treatment (5mg/kg) and were thereafter tested for PPI. PCP induced deficits in PPI were ameliorated by prefrontal PCP (0.1mM) treatment whereas PPI was not affected by prefrontal cortex PCP administration per se at any of the doses tested. Taken together, inhibition of NMDA receptors in the PFC does not seem to be enough to impair PPI per se but NMDA receptor mediated signalling in the PFC may be a key factor for the PPI-disruptive effects of global NMDA receptor inhibition. This indicates that targeting PFC NMDA receptor signalling may have potential as a treatment target for schizophrenia although further studies are needed to understand pharmacology and pathophysiological role of PFC NMDA receptors.
    European neuropsychopharmacology: the journal of the European College of Neuropsychopharmacology 03/2011; 21(3):248-53. · 3.68 Impact Factor
  • Article: A functional Toll-like receptor 3 gene (TLR3) may be a risk factor for tick-borne encephalitis virus (TBEV) infection.
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    ABSTRACT: Tick-borne encephalitis virus (TBEV) infections may be asymptomatic or cause severe symptoms in the central nervous system. A mutation in the chemokine receptor 5 gene has been associated with increased risk of TBE but explains only a limited number of cases. Investigations of further risk factors are needed. To investigate the importance of the innate immune response, we analyzed 128 TBE patients, 77 patients with aseptic meningoencephalitis (AME) and 135 healthy controls, for 3 mutations: 2 in the Toll-like receptor 3 (TLR3) gene and 1 in the 2'-5'-oligoadenylate synthetase (OAS1) gene. Although no association was found between the mutation in the OAS1 gene and TBE, the genotype distribution ofrs3775291, a mutation in TLR3, differed significantly between TBE patients and controls; 61%, 32%, and 7% of the TBE patients were carriers of the wild-type, heterozygous, and mutant genotype of rs3775291, respectively. The corresponding percentages among healthy controls (n = 126) were 52%, 29%, and 19% (P = .02), and among AME patients (n = 75) were 47%, 32%, and 21% (P = .009). Additionally, the wild-type rs3775291 allele was more common among TBE patients than among healthy controls (allele frequency, .768 vs .663; P = .01). A functional TLR3 is a risk factor for TBEV infection.
    The Journal of Infectious Diseases 02/2011; 203(4):523-8. · 6.41 Impact Factor
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    Article: L-lysine as adjunctive treatment in patients with schizophrenia: a single-blinded, randomized, cross-over pilot study.
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    ABSTRACT: Accumulating evidence suggests that the brain's nitric oxide (NO) signalling system may be involved in the pathophysiology of schizophrenia and could thus constitute a novel treatment target. The study was designed to investigate the benefit of L-lysine, an amino acid that interferes with NO production, as an add-on treatment for schizophrenia. L-lysine, 6 g/day, was administered to 10 patients with schizophrenia as an adjunctive to their conventional antipsychotic medication. The study was designed as a single-blinded, cross-over study where patients were randomly assigned to initial treatment with either L-lysine or placebo and screened at baseline, after four weeks when treatment was crossed over, and after eight weeks. L-lysine treatment caused a significant increase in blood concentration of L-lysine and was well tolerated. A significant decrease in positive symptom severity, measured by the Positive And Negative Syndrome Scale (PANSS), was detected. A certain decrease in score was also observed during placebo treatment and the effects on PANSS could not unequivocally be assigned to the L-lysine treatment. Furthermore, performance on the Wisconsin Card Sorting Test was significantly improved compared to baseline, an effect probably biased by training. Subjective reports from three of the patients indicated decreased symptom severity and enhanced cognitive functioning. Four-week L-lysine treatment of 6 g/day caused a significant increase in blood concentration of L-lysine that was well tolerated. Patients showed a significant decrease in positive symptoms as assessed by PANSS in addition to self-reported symptom improvement by three patients. The NO-signalling pathway is an interesting, potentially new treatment target for schizophrenia; however, the effects of L-lysine need further evaluation to decide the amino acid's potentially beneficial effects on symptom severity in schizophrenia.
    BMC Medicine 01/2011; 9:40. · 6.03 Impact Factor
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    Article: Low prevalence of rotavirus and high prevalence of norovirus in hospital and community wastewater after introduction of rotavirus vaccine in Nicaragua.
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    ABSTRACT: Rotavirus (RV) and norovirus (NoV) are major causes of pediatric diarrhea and are altogether associated with approximately 800,000 deaths in young children every year. In Nicaragua, national RV vaccination program using the pentavalent RV5 vaccine from Merck was implemented in October 2006. To determine whether RV vaccination decreased the overall number of RV infections, we investigated the occurrence of RV and NoV in wastewater in the city of León from July 2007 to July 2008 and compared these data with pre-vaccination data. The major finding was the low prevalence of RV compared to NoV in all sampling points (11% vs 44%, p<0.05), and that RV concentration was lower as compared to NoV. RV was observed mainly during the rainy season (July-September), and the majority of all RV detected (6/9) belonged to subgroup (SG) I. The partial VP7-gene obtained from one RV positive sample was similar (99% nt identity) to a G6 VP7-gene of bovine origin and similar to the corresponding gene of the vaccine strain (98%). Furthermore RV G-types 2 and 4 were found in the incoming wastewater. NoV strains were detected throughout the year, of which a majority (20/21) were of genotype GII.4. We conclude that the introduction of RV vaccination reduced the transmission of RV in the community in Nicaragua. However, the burden of diarrhea in the country remains high, and the high prevalence of NoVs in hospital and municipal wastewater is noteworthy. This study highlights the need for further assessment of NoV following RV vaccine introduction.
    PLoS ONE 01/2011; 6(10):e25962. · 4.09 Impact Factor
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    Article: Intestinal epithelial stem/progenitor cells are controlled by mucosal afferent nerves.
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    ABSTRACT: The maintenance of the intestinal epithelium is of great importance for the survival of the organism. A possible nervous control of epithelial cell renewal was studied in rats and mice. Mucosal afferent nerves were stimulated by exposing the intestinal mucosa to capsaicin (1.6 mM), which stimulates intestinal external axons. Epithelial cell renewal was investigated in the jejunum by measuring intestinal thymidine kinase (TK) activity, intestinal (3)H-thymidine incorporation into DNA, and the number of crypt cells labeled with BrdU. The influence of the external gut innervation was minimized by severing the periarterial nerves. Luminal capsaicin increased all the studied variables, an effect nervously mediated to judge from inhibitory effects on TK activity or (3)H-thymidine incorporation into DNA by exposing the mucosa to lidocaine (a local anesthetic) or by giving four different neurotransmitter receptor antagonists i.v. (muscarinic, nicotinic, neurokinin1 (NK1) or calcitonin gene related peptide (CGRP) receptors). After degeneration of the intestinal external nerves capsaicin did not increase TK activity, suggesting the involvement of an axon reflex. Intra-arterial infusion of Substance P (SP) or CGRP increased intestinal TK activity, a response abolished by muscarinic receptor blockade. Immunohistochemistry suggested presence of M3 and M5 muscarinic receptors on the intestinal stem/progenitor cells. We propose that the stem/progenitor cells are controlled by cholinergic nerves, which, in turn, are influenced by mucosal afferent neuron(s) releasing acetylcholine and/or SP and/or CGRP. In mice lacking the capsaicin receptor, thymidine incorporation into DNA and number of crypt cells labeled with BrdU was lower than in wild type animals suggesting that nerves are important also in the absence of luminal capsaicin, a conclusion also supported by the observation that atropine lowered thymidine incorporation into DNA by 60% in control rat segments. Enteric nerves are of importance in maintaining the intestinal epithelial barrier.
    PLoS ONE 01/2011; 6(2):e16295. · 4.09 Impact Factor
  • Article: Asymptomatic norovirus infections in Nicaraguan children and its association with viral properties and histo-blood group antigens.
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    ABSTRACT: It has been previously reported that histo-blood group antigens (HBGAs) and particularly secretor status provides protection against symptomatic norovirus infection, but it remains unclear to what extent this includes asymptomatic infections in children. To explore whether HBGAs or certain viral genotypes are associated with asymptomatic norovirus infections in a pediatric population in Nicaragua, we investigated 163 children ≤5 years of age, without a recent history of diarrhea (≤10 days). Asymptomatic norovirus infections were observed in 11.7% (19/163), with children ≤6 months of age being most frequently infected (16%). Of the 19 norovirus-positive children, 4 (21%) and 10 (53%) were infected with genogroups GI and GII, respectively, and 4 children (21%) were infected with viruses of both genogroups. Most children had ≥10 viral genomes per gram of feces. Nucleotide sequence analysis (15/19) revealed uncommon genotypes, such as, GII.7 (n = 5) and GII.2 (n = 3). An interesting observation was the low frequency of norovirus GII.4 strains among the asymptomatic children. AB blood type, Lewis a (Le) phenotype and nonsecretor genotype (sese) were not found among the asymptomatic children, but they occurred in population controls. Frequency of asymptomatic norovirus infections was similar to that observed in symptomatic children from Nicaragua. Norovirus GII.2 and GII.7 were frequently detected but the globally dominating GII.4 was infrequent. Host genetic factors previously observed to be associated with protection against symptomatic norovirus infection were not found in this study.
    The Pediatric Infectious Disease Journal 10/2010; 29(10):934-9. · 3.58 Impact Factor
  • Article: Human antibody responses to bovine (Newbury-2) norovirus (GIII.2) and association to histo-blood group antigens.
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    ABSTRACT: Serum antibodies to bovine norovirus have been found recently in about 22% of humans. Whether this prevalence reflects limited virulence properties of the virus or that inherited host factors provide protection against bovine norovirus infection in humans remains to be established. To investigate whether histo-blood group antigens correlate with the presence of bovine norovirus (GIII.2) antibody, plasma (n = 105) from Swedish blood donors, genotyped and phenotyped for secretor, Lewis and ABO, were tested and compared for the frequency of IgG antibody and antibody titer to Bo/Newbury2/76/UK. In total, 26.7% (28/105) of Swedish blood donors were antibody-positive. Two non-secretors (2/21, 9.5%) were antibody-positive compared with 26/84 (31%) secretors (P = 0.047). While no statistically significant correlation was found between the frequency of antibodies to bovine norovirus and different ABO blood groups, individuals with blood type B presented the highest frequency of antibodies (37.5%) compared with 0-30% among other blood groups. Individuals with Le(a-b+) had not only higher frequency of antibodies (31.3%) compared with Le(a+b-) (11%) (P = 0.068) but also higher antibody titer (P = 0.085) although this was not significant statistically. No detectable cross-reaction between bovine GIII.2 and human GII.3 NoV VLP was found with human and animal sera. The results of this study suggest that bovine norovirus infections occur in Sweden and that secretor status but not ABO blood groups is a possible risk factor for infection.
    Journal of Medical Virology 07/2010; 82(7):1241-6. · 2.82 Impact Factor
  • Article: Novel light-upon-extension real-time PCR assay for simultaneous detection, quantification, and genogrouping of group A rotavirus.
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    ABSTRACT: We have developed a light-upon-extension (LUX) real-time PCR assay for detection, quantification, and genogrouping of group A rotavirus (RV), the most common cause of acute gastroenteritis in children. The LUX system uses a fluorophore attached to one primer and having a self-quenching hairpin structure, making it cost-effective and specific. We designed genogroup-specific primers having different fluorophores, making it possible to differentiate between the two main genogroups of human group A RVs. The assay was applied on clinical stool specimens from Sweden and Central America (n=196) and compared to immunological and conventional PCR assays. The genogrouping ability was further validated against a subset of clinical specimens, which had been genogrouped using monoclonal antibodies. Our real-time PCR assay detected and quantified all positive specimens (n=145) and exhibited higher sensitivity than immunological assays and conventional PCR. The assay exhibited a wide dynamic range, detecting from 5 to >10(7) genes per PCR, resulting in a theoretical lower detection limit of <10,000 viruses per gram of stool. No cross-reaction was observed with specimens containing norovirus, sapovirus, astrovirus, or adenovirus. In total, 22 (15%) of the positive clinical specimens were identified as genogroup I, 122 (84%) were identified as genogroup II, and 1 specimen was found to contain a mix of both genogroups. All genogroup I-positive specimens were associated with capsid glycoprotein 2 (G2). No significant difference in viral load was found between genogroups or geographic region. The detection and quantification, combined with the genogrouping ability, make this assay a valuable tool both for diagnostics and for molecular epidemiological investigations.
    Journal of clinical microbiology 03/2010; 48(5):1859-65. · 4.16 Impact Factor
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    Article: Norovirus gastroenteritis outbreak with a secretor-independent susceptibility pattern, Sweden.
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    ABSTRACT: Norovirus (NoV) is recognized as the commonest cause of acute gastroenteritis among adults. Susceptibility to disease has been associated with histo-blood group antigens and secretor status; nonsecretors are almost completely resistant to disease. We report a foodborne outbreak of GI.3 NoV gastroenteritis that affected 33/83 (40%) persons. Symptomatic disease was as likely to develop in nonsecretors as in secretors (odds ratio [OR] 1.41, 95% confidence interval [CI] 0.46-4.36 vs. OR 0.71, 95% CI 0.23-2.18, p = 0.57). Moreover, no statistical difference in susceptibility was found between persons of different Lewis or ABO phenotypes. The capsid gene of the outbreak strain shares high amino acid homology with the Kashiwa645 GI.3 strain, previously shown to recognize nonsecretor saliva, as well as synthetic Lewis a. This norovirus outbreak affected persons regardless of secretor status or Lewis or ABO phenotypes.
    Emerging Infectious Diseases 01/2010; 16(1):81-7. · 6.79 Impact Factor

Institutions

  • 2006–2012
    • Linköping University
      • Department of Clinical and Experimental Medicine
      Linköping, OEstergoetland, Sweden
    • University of Valencia
      • Departamento de Microbiología y Ecología
      Valencia, Valencia, Spain
    • University Hospital Linköping
      Linköping, OEstergoetland, Sweden
  • 2005–2011
    • University of Gothenburg
      • • Department of Physiology
      • • Department of Pharmacology
      Göteborg, Vaestra Goetaland, Sweden
    • Institut Français de Recherche pour l'Exploitation de la Mer
      • Laboratory of Microbiology
      Issy-les-Moulineaux, Ile-de-France, France
  • 2004–2011
    • Sahlgrenska University Hospital
      Göteborg, Vaestra Goetaland, Sweden
  • 2003–2008
    • Karolinska Institute
      Stockholm, Stockholm, Sweden
  • 2007
    • Université de Nantes
      Nantes, Pays de la Loire, France
    • National Autonomous University of Nicaragua
      Managua, Departamento de Managua, Nicaragua
    • AstraZeneca
      Stockholm, Stockholm, Sweden
  • 1999–2005
    • Swedish Institute for Communicable Disease Control
      Stockholm, Stockholm, Sweden
  • 2002
    • Lund University
      Lund, Skane, Sweden