Lars Magnius

Sahlgrenska University Hospital, Goeteborg, Västra Götaland, Sweden

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Publications (129)469.14 Total impact

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    ABSTRACT: Determination of anti-hepatitis E virus antibodies (anti-HEV) is still enigmatic. There is no gold standard, and results obtained with different assays often diverge. Herein, five assays were compared for detection of anti-HEV IgM and IgG. Sera from 500 Swedish blood donors and 316 patients, of whom 136 had suspected HEV infection were analysed. Concordant results for IgM and IgG with all assays were obtained only for 71% and 70% of patients with suspected hepatitis E. The range of sensitivity for anti-HEV detection was broad, 42% to 96%, which was reflected in the detection limit varying up to 19-fold for IgM and 17-fold for IgG between assays. HEV RNA was analysed in all patients and in those blood donors reactive for anti-HEV in any assay and was found in 26 individuals. Amongst all assays, both anti-HEV IgG and IgM were detected in ten individuals, whereas twelve had only IgG, and seven of those twelve only with the two most sensitive assays. Three of the HEV RNA positive samples were negative for both anti-HEV IgM and IgG in all assays. With the two most sensitive assays, anti-HEV IgG was identified in 16% of the blood donor samples, and in 66% of patients with suspected HEV infection. Because several HEV RNA positive samples had only anti-HEV IgG without anti-HEV IgM, or lacked anti-HEV antibodies, analysis for HEV RNA may be warranted as a complement in the laboratory diagnosis of ongoing HEV infection.
    No preview · Article · Dec 2015 · Journal of Clinical Microbiology
  • Heléne Norder · Lars Magnius

    No preview · Article · Mar 2015 · The Lancet Infectious Diseases
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    ABSTRACT: The prevalence of HBsAg and its subtypes and hepatitis B virus (HBV) genotypes in native population groups of five Siberian regions—the Republic of Altai, Kemerovo oblast, Irkutsk oblast, Yamalo-Nenet autonomous oblast (the YaNAO), and Kransnoyarsk krai (a total of 5657 samples)—was studied. Statistically significant differences were found in these groups for the studied HBV markers and types. HBsAg was the most prevalent in Altaians in Republic of Altai (13.4% of samples); Dolgans and Nganasans in Krasnoyarsk krai (13.2%); Teleuts in Kemerovo oblast (10.2%); and Buryats in Irkutsk oblast (5.4-8.2%). HBsAg prevalence was minor in Khants, Komi, Nenets and Selkups in YaNAO (0.7-1.7%). The study of the partial HBsAg-gene sequences of 143 HBV isolates from different groups of the five Siberian regions revealed that 130 (90.9%) belonged to genotype D (subtypes ayw2 and ayw3), 10 (7%) to genotype C (subtype adrq+), and 3 (2.1%) to genotype A (subtype adw2). Of the 130 genotype D isolates, 120 belonged to subgenotypes D1 (34.3%), D2 (22.4%), and D3 (27.3%), while the genotype was not determined in 10 (7%) isolates. Subgenotype D1 (HBsAg subtype ayw2) was prevalent among Kazakhs in the Republic of Altai (85.7% of the strains), Teleuts in Kemerovo oblast (60.0%), Russians in Irkutsk oblast (87.5%), and Dolgans and Nganasans in Krasnoyarsk krai (68.8%). Subgenotype D2 (subtype ayw3) was prevalent among Khants and Komi (75%) and Nentsi (57.1%) from the YaNAO. Subgenotype D3 (subtype ayw2) was prevalent in Altaians in the Republic of Altai (76.2%) and Buryats from Irkutsk oblast (50%). Significant prevalence of genotype C (subgenotype C1, 18.8%) was first found in the Far North of Siberia (Taimyr Peninsula, Krasnoyarsk krai). On the basis of the obtained data, we suggested that there exist several epidemiologically different sources of HBV expansion in native Siberian population groups.
    Full-text · Article · Jan 2015 · Molecular Genetics Microbiology and Virology
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    ABSTRACT: Most persons infected with enterically transmitted viruses shed high amounts of virus in feces for days or weeks, both before and after onset of symptoms. Therefore viruses causing gastroenteritis may be detected in wastewater, even if only a few persons are infected. In this study, the presence of nine pathogenic viruses was investigated in sewage (norovirus, astrovirus, rotavirus, adenovirus, enterovirus, Aichi virus, parechovirus, hepatitis A (HAV) virus and hepatitis E virus) to explore whether their identification could be used as an early warning of outbreaks. Samples of the untreated sewage were collected in proportion to flow at Ryaverket (Gothenburg, Sweden). Daily samples collected during every second week between January and May 2013 were pooled and analysed for detection of viruses by concentration through adsorption to milk proteins and PCR. The largest amount of noroviruses was detected in sewage two to three weeks before the most patients were diagnosed with this infection in Gothenburg. The other viruses were detected in lower levels. HAV was detected between weeks 5 and 13, and partial sequencing of the structural VP1protein identified three different strains. Two strains were involved in an ongoing outbreak in Scandinavia, and were also identified in samples from patients with acute hepatitis A in Gothenburg during spring of 2013. The third strain was unique and not detected in any patient sample. The method used may thus be a tool to detect incipient outbreaks of these viruses and provide early warning before the causative pathogens have been recognized in health care.
    Preview · Article · Aug 2014 · Applied and Environmental Microbiology
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    ABSTRACT: Complete coding regions were sequenced for two new enterovirus genomes: EV-B93 previously identified by VP1 sequencing, derived from a child with acute flaccid paralysis in the Democratic Republic of Congo; and EV-C95 from a French soldier with acute gastroenteritis in Djibouti. The EV-B93 P1 had more than 30% nucleotide divergence from other EV-B types, with highest similarity to E-15 and EV-B80. The P1 nucleotide sequence of EV-C95 was most similar, 71%, to CV-A21. Complete coding regions for the new enteroviruses were compared with those of 135 EV-B and 176 EV-C strains representing all types available in GenBank. When strains from the same outbreak or strains isolated during the same year in the same geographical region were excluded, 27 of the 58 EV-B, and 16 of the 23 EV-C types were represented by more than one sequence. However, for EV-B the P3 sequences formed three clades mainly according to origin or time of isolation, irrespective of type, while for EV-C the P3 sequences segregated mainly according to disease manifestation, with most strains causing paralysis, including polioviruses, forming one clade, and strains causing respiratory illness forming another. There was no intermixing of types between these two clades, apart from two EV-C96 strains. The EV-B P3 sequences had lower inter-clade and higher intra-clade variability as compared to the EV-C sequences, which may explain why inter-clade recombinations are more frequent in EV-B. Further analysis of more isolates may shed light on the role of recombinations in the evolution of EV-B in geographical context. J. Med. Virol. 2014. © 2014 Wiley Periodicals, Inc.
    No preview · Article · Aug 2014 · Journal of Medical Virology
  • Erik Lycke · Lars O Magnius · Helene Norder

    No preview · Article · Mar 2014 · The Lancet
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    ABSTRACT: Mutations in the human hepatitis B virus (HBV) genome contribute to its escape from host immune surveillance and result in persistent infections. The aim of this study was to characterize the molecular variations of the surface gene and protein in chronically-infected patients from the southern part of Iran. The surface genes from 12 HBV chronic carriers were amplified, sequenced and subsequently aligned using international and national Iranian database. All strains belonged to genotype D, subgenotype D1 and subtype ayw2. Of all 30 muta-tions occurred at 22 nucleotide positions, 18 (60%) were missense (amino acid altering) and 12 (40%) were silent (no amino acid changing). The mean mutation frequency (missense to silent nucleotide ratio), was 1.5, indicating application of a high positive selection pressure on the surface proteins. At the amino acid level, of 17 substitutions, 15 (88%) occurred in different immune epitopes within surface protein, of which 7 (46.6%) in B cell epitopes in 5 residues; 7 (46.6%) in T helper epitopes in 6 positions; 1 (7%) in inside CTL epitopes in 1 residue. We therefore conclude that the distribution of 93.2% of amino acid mutations inside B and T helper immune epitopes as well as the ratio between silent and missense nucleotide mutations showed a positive, focused immune selection pressure on the surface protein, which led to the evolution and emergence of escape mutants in these patients.
    Full-text · Article · Sep 2013 · Iranian journal of allergy, asthma, and immunology
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    ABSTRACT: Hepatitis C is prevalent among thalassemia patients in Iran. It is mainly transfusion mediated, in particular among patients treated before 1996 when blood screening was introduced. The current study aimed to investigate why patients still seroconvert to anti-HCV in Iranian thalassemia centers. During 2006-2007 sera were sampled from 217 anti-HCV positive thalassemia patients at nine thalassemia centers in Tehran and Amol city, where 34 (16%) patients had been infected after 1996. The HCV subtype could be determined by sequencing and phylogenetic analysis of partial NS5B and/or 5׳NCR-core region in 130 strains. 1a (53%) was predominant followed by 3a (30%), 1b (15%), and one strain each of 2k, 3k and 4a. Phylogenetic analysis revealed 19 clades with up to five strains diverging with less than six nucleotides from each other within subtypes 1a and 3a. Strains in seven clades were from nine patients infected between 1999 and 2005 and similar to strains from eight patients infected before 1996, indicating ongoing transmission at the centers. Further epidemiological investigation revealed that 28 patients infected with strains within the same clade had frequently been transfused at the same shift sitting on the same bed. An additional eight patients with related strains had frequently been transfused simultaneously in the same room. The results suggest nosocomial transmission at these thalassemia centers both before and after the introduction of blood screening. Further training of staff and strict adherence to preventive measures are thus essential to reduce the incidence of new HCV infections.
    Full-text · Article · Jan 2013 · Hepatitis Monthly
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    ABSTRACT: Serological markers and DNA of hepatitis B virus (HBV) were detected in 487 blood samples of aboriginal people in the Alar district of the Irkutsk region (mostly Buryat) in 2005. HBsAg was found in 40 (8.2%) samples. HBV DNA was found in 24 out of 40 (60%) HBsAg-positive samples. HBV-positive DNA samples were found to contain nucleotide sequences of the Pre-S1, Pre-S2, and S regions of the HBV genome with a total length of 1146 n. 22 out of 24 (92%) isolates were found to belong to the D genotype, two belonged to the C genotype; eight (33.3%) belonged to the D3 subgenotype, six (25.0%) belonged to the D2 subgenotype, one (4.1%) belonged to the D1 subgenotype, and nine (37.5%) belonged to unidentified subgenotype. The incidence of the HBsAg subtype was determined to be ayw2 in 14 out of 24 (58.3%) isolates and ayw3 in seven (29.2%) isolates; the subtype was not identified for one (4.1%) isolate. In two C-genotype isolates, the subtypes were identified as adw2 and adrq+. A comparative analysis of the results of this work and those obtained previously for native people of Yamalo-Nenets Autonomous District (YaNAD, mostly Khanty and Komi) demonstrated significant differences in the incidence in YaNAD of HBsAg (3.2% isolates, p > 0.999), subgenotype D2 (62% isolates, p > 0.95), and subtype ayw3 (70.6% isolates; p > 0.95). The variability in the incidence of two variants in two groups of native Siberian peoples is the evidence of different infection sources in these populations. Keywordsincidence–hepatitis B virus–subvirus genotype–HBsAg subtype–native people–Siberia
    No preview · Article · Dec 2010 · Molecular Genetics Microbiology and Virology
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    ABSTRACT: The prevalence of hepatitis B virus (HBV) markers was investigated in 563 inhabitants aged 15-55 years from a sugar cane region, Sirama, and from a village, Mataipako, in Northern Madagascar. Serological markers of past or present infection were significantly higher in Sirama, 74% versus 45%. There was no difference in the prevalence of chronic HBsAg carriers, 8.7% versus 8.5% between the two regions. Sequencing the S gene in 45 strains revealed a predominance of genotype E, in 53%, followed by subgenotype A1 in 22%, and genotype D in 18%. Phylogenetic analyses of the genotype E strains showed homology with West African strains. All A1 isolates were similar to Malawi strains. Most genotype D strains were subgenotype D7 and related to strains from Somalia and Tunisia. One genotype D strain formed a branch between Pacific D4 and African D7 strains at neighbor-joining analysis. The pre-core stop mutant was found in 33% of the genotype D strains, 17% of E but not in any A1 strain. The high prevalence and low variability of genotype E strains in only two villages, indicates a rather recent introduction of this genotype into Madagascar from West Africa, possibly through migration or slave trade. The wider spread and genetic relationship of genotype D with East African and Austronesian strains indicate an earlier introduction of this genotype. Molecular epidemiology of HBV may thus be used to complement linguistic and genetic studies on past human migrations in Africa.
    Full-text · Article · Sep 2010 · Journal of Medical Virology
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    ABSTRACT: Amassments of heterochromatin in somatic cells occur in close contact with the nuclear envelope (NE) but are gapped by channel- and cone-like zones that appear largely free of heterochromatin and associated with the nuclear pore complexes (NPCs). To identify proteins involved in forming such heterochromatin exclusion zones (HEZs), we used a cell culture model in which chromatin condensation induced by poliovirus (PV) infection revealed HEZs resembling those in normal tissue cells. HEZ occurrence depended on the NPC-associated protein Tpr and its large coiled coil-forming domain. RNAi-mediated loss of Tpr allowed condensing chromatin to occur all along the NE's nuclear surface, resulting in HEZs no longer being established and NPCs covered by heterochromatin. These results assign a central function to Tpr as a determinant of perinuclear organization, with a direct role in forming a morphologically distinct nuclear sub-compartment and delimiting heterochromatin distribution.
    Full-text · Article · May 2010 · The EMBO Journal
  • Stephan Schaefer · Lars Magnius · Helene Norder
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    No preview · Article · Sep 2009 · Intervirology
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    ABSTRACT: Recent studies have suggested that Cytotoxic T lymphocytes (CTL) play a key role in eliminating hepatitis B virus (HBV). We aimed to investigate the role of mutations in different immune epitopes of hepatitis B core antigen (HBcAg) among Iranians with hepatitis B e antigen negative chronic hepatitis B (e-CHB), and asymptomatic carriers (ASCs). Amino acids 1-150 of HBcAg were characterized for HBV strains from 29 e-CHB patients and 48 ASCs from Iran. All patients were infected with HBV genotype D and had previously been investigated for the presence of pre-core and basic core promoter (BCP) mutants. Amino acid mutations of core protein were observed more frequently in HBV strains from ASCs than e-CHB patients (p=0.014). Asn(67) mutation was mutually exclusive to the combination Ile(66) and Ser(69) (P<0.001). Substitutions for Ser(21) and Thr12Ser were associated with lower serum levels of HBV DNA (p<0.001). None of the patients with mutations in HLA-A2 CTL epitope, 18-27, had serum HBV DNA more than 10(5)copies/mL (p<0.001). By multivariate analysis, high level (>10(5)copies/mL) of serum HBV DNA was inversely associated with the presence of mutations in CTL epitopes of HBc (OR: 0.11, p=0.015), while it was directly associated with the presence of promoter double T(1762)A(1764) mutations together with G(1757) (OR: 16.87, p=0.004). The inverse correlation between serum levels of HBV DNA and CTL escape mutations of the core protein in HBeAg seroconverted patients, supports the notion that selection of CTL escape mutations consolidates the persistence of HBV infection despite reducing viral fitness.
    Full-text · Article · Sep 2009 · Journal of clinical virology: the official publication of the Pan American Society for Clinical Virology
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    Full-text · Article · May 2009 · Gastroenterology

  • No preview · Article · Apr 2009 · Lakartidningen
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    ABSTRACT: In order to define hepatitis B virus (HBV) mutational patterns in Iran, nucleotide sequences obtained from 91 patients and encompassing the precore, basal core promoter (BCP) and surface (S) regions, were compared. The patients were grouped as asymptomatic carriers, chronic active hepatitis or cirrhotic patients. Genotypes and mutations were determined by sequencing and phylogenetic analysis. All strains belonged to genotype D, and most of them to subgenotype D1. All but two strains specified ayw2, one ayw3 and one adw2 determinants. Two deletions of 8- or 20-bp were found in the X region in eight strains, six from patients with chronic active hepatitis. Eight of 21 strains from patients with cirrhosis harboured unusual mutations such as a stop codon at position 69 in the S region or a previously not described mutation in the BCP region ((1761)TC/ATTTG(1766)). All patients infected by strains with the stop codon mutation had detectable HBsAg and high viral load. The accumulation of mutations found in the BCP and S regions in HBV strains from patients with chronic active hepatitis and cirrhosis may predict disease progression in Iranian HBsAg carriers.
    Full-text · Article · Mar 2009 · Journal of Viral Hepatitis
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    ABSTRACT: Antibodies against hepatitis E virus (anti-HEV) were found in 248 Swedish and Danish patients between 1993 and 2007. Most patients were symptomatic and tested for anti-HEV due to travel abroad. Among patients with known country of infection, most were infected in Asia, mainly on the Indian subcontinent. However, 29 patients were infected in Europe, nine of these had HEV IgM and/or HEV RNA in serum. In sera from 65 of 141 tested patients HEV RNA could be detected, and 63 strains could be typed by limited sequencing within ORF2. HEV RNA was found in sera from 71% of the patients with HEV IgM and IgG and in 18% of the patients with only detectable HEV IgG. It was also found up to three weeks after the onset of disease in 67% of the patients with known date of onset. Patients infected in Europe were infected by genotype 3, and were older than those infected by genotype 1 (mean age 55.3 vs 30 years, p<0.001). Since it is known that genotype 3 can infect domestic pigs, HEV strains from 18 piglets in 17 herds in Sweden and Denmark were sequenced. Phylogenetic analyses of the genotype 3 strains showed geographical clades and high similarity between strains from patients and pigs from the same area. There are thus autochthonous hepatitis E cases in Scandinavia, and there are probably many undiagnosed ones. Patients with hepatitis of unknown etiology should therefore be investigated for anti-HEV even if they have not been outside Europe, since infections acquired from pigs or other animals should be taken into consideration.
    No preview · Article · Feb 2009 · Eurosurveillance: bulletin europeen sur les maladies transmissibles = European communicable disease bulletin
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    ABSTRACT: Complete or almost complete hepatitis B virus (HBV) genomes were sequenced for 13 genotype A and 42 genotype D strains from the former USSR. The strains were classifiable within subgenotypes A2, D1, D2 and D3. Comparison of the deduced gene products for the four ORFs of 89 genotype D strains revealed 27 subgenotype-specific residues, and a region spanning residues 58-128 in the spacer region of the P gene could be used to distinguish between D1 and D4. This enabled the allocation to subgenotype of strains with partially sequenced genomes. D2 was dominating, while D3 was found in low frequency in the whole region. D1 was most prevalent in the Middle Asian Republics. Mean inter-subgenotype divergences between D1 and D2, D1 and D3 and D2 and D3 were 2.7, 3.4 and 3.4 %, respectively. The intra-subgenotype divergence was 0.4, 1.1, 1.0 and 1.8 % for A2, D1, D2 and D3, respectively. All D1 and D3 strains encoded subtype ayw2, whereas most D2 strains encoded ayw3. Two D2 strains encoded ayw4. Strains with identical S genes were closely related at the level of complete genomes and formed geographically specific clades with low intraclade divergences, possibly indicating past iatrogenic spread. It is not clear whether the finding of four subgenotypes in the area corresponds to separate introductions of the virus or to previous population migrations into the area. An earlier introduction of D3 compared with D2 was supported by its higher intra-subgenotype divergence, while the lower divergence within D1 is probably due to a more recent emergence.
    Full-text · Article · Aug 2008 · Journal of General Virology
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    ABSTRACT: The genus Enterovirus (family Picornaviridae) contains five species with strains isolated from humans: Human enterovirus A (HEV-A), HEV-B, HEV-C, HEV-D and Poliovirus. In this study, a proposed new serotype of HEV-D was characterized. Four virus strains were isolated from sewage in Egypt and one strain from acute flaccid paralysis cases in the Democratic Republic of the Congo. The complete genome of one environmental isolate, the complete coding sequence of one clinical isolate and complete VP1 regions from the other isolates were sequenced. These isolates had 66.6-69.4% nucleotide similarity and 74.7-76.6% amino acid sequence similarity in the VP1 region with the closest enterovirus serotype, enterovirus 70 (EV70), suggesting that the isolates form a new enterovirus type, tentatively designated enterovirus 94 (EV94). Phylogenetic analyses including sequences of the 5' UTR, VP1 and 3D regions demonstrated that EV94 isolates formed a monophyletic group within the species HEV-D. No evidence of recombination was found between EV94 and the other HEV-D serotypes, EV68 and EV70. Further biological characterization showed that EV94 was acid stable and had a wide cell tropism in vitro. Attempts to prevent replication with protective antibodies to known enterovirus receptors (poliovirus receptor, vitronectin alphavbeta3 receptor and decay accelerating factor) were not successful. Seroprevalence studies in the Finnish population revealed a high prevalence of this virus over the past two decades.
    Full-text · Article · Apr 2007 · Journal of General Virology
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    ABSTRACT: During the last decade, there has been a dramatic increase in intravenous drug use in young adults in Estonia with an increased incidence of both hepatitis B and C as a consequence. Since genetic data are limited regarding hepatitis C virus (HCV) strains in Estonia, the aim of the study was to characterize HCV strains in different risk groups to determine their relatedness to strains from other geographical regions. Three hundred fifty-three anti-HCV positive sera collected during 1994-2004 from hospitalized patients, blood donors and health care workers were used as source of HCV RNA. Two hundred nine (59%) of the sera were positive for HCV RNA by PCR directed to the 5'-UTR region. For 174 strains the HCV subtype was determined by analyses of the NS5B and/or the 5'UTR-core regions. 1b (71%) was the most common subtype followed by 3a (24%), 2c (2%), 1a (1%), and 2a (1%). The 1b and 3a strains were similar to strains from other regions of the former USSR. Within genotype 1b there were several HCV lineages. However, for 3a there seemed to be two separate introductions into Estonia. There was a relative shift from subtype 1b to 3a in 1999-2000 with a further replacement of 3a with 1b in intravenous drug users in 2001 and onwards (P < 0.05). However, both subtypes were found to co-circulate in the community independent of risk factors. One patient was infected with the 2k/1b recombinant presumed to originate from St. Petersburg being the first isolate of this recombinant recovered outside Russia.
    Full-text · Article · Apr 2007 · Journal of Medical Virology

Publication Stats

6k Citations
469.14 Total Impact Points

Institutions

  • 2015
    • Sahlgrenska University Hospital
      Goeteborg, Västra Götaland, Sweden
  • 1997-2015
    • Swedish Institute for Communicable Disease Control
      Tukholma, Stockholm, Sweden
  • 1991-2014
    • Karolinska Institutet
      • • Institutionen för medicin, Huddinge
      • • Department of Infectious Diseases
      Сольна, Stockholm, Sweden
  • 2013
    • Tehran University of Medical Sciences
      Teheran, Tehrān, Iran
  • 2007
    • National Public Health Institute
      Helsinki, Southern Finland Province, Finland
  • 2006
    • University of Tartu
      Dorpat, Tartu, Estonia
    • Saint Petersburg Medical Academy
      Sankt-Peterburg, St.-Petersburg, Russia
    • Shahid Beheshti University of Medical Sciences
      Teheran, Tehrān, Iran
  • 1994-2005
    • Uppsala University Hospital
      • Department of Infectious Diseases
      Uppsala, Uppsala, Sweden
    • Somali National University
      Muqdisho, Banaadir, Somalia
  • 1998-2003
    • Instituto de Salud Carlos III
      Madrid, Madrid, Spain
    • University of Zulia
      Maracaibo, Estado Zulia, Venezuela
  • 2001
    • Norrlands universitetssjukhus
      Umeå, Västerbotten, Sweden
  • 1995
    • Institut de Cancérologie Gustave Roussy
      Villejuif, Île-de-France, France
  • 1992-1994
    • Institut National de la Transfusion Sanguine, Paris
      Lutetia Parisorum, Île-de-France, France
  • 1993
    • Karolinska University Hospital
      Tukholma, Stockholm, Sweden
  • 1988
    • Örebro University Hospital
      • Department of Infectious Diseases
      Örebro, Örebro, Sweden