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  • 1. Al-Saai, Salma
    et al.
    Kheir, Amany
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Abdel-Muhsin, Abdel-Muhsin A
    Al-Ghazali, Aisha
    Nwakanma, Davis
    Swedberg, Göte
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Babiker, Hamza A
    Distinct haplotypes of dhfr and dhps among Plasmodium falciparum isolates in an area of high level of sulfadoxine-pyrimethamine (SP) resistance in eastern Sudan2009In: Infection, Genetics and Evolution, ISSN 1567-1348, E-ISSN 1567-7257, Vol. 9, no 5, p. 778-783Article in journal (Refereed)
    Abstract [en]

    Typing of polymorphic microsatellites that are linked to drug resistance genes has shed light on the origin and pattern of spread of some anti-malarial drugs. Recent surveys revealed spread of a high-level pyrimethemine resistant lineage of Plasmodium falciparum, of Asian origin, across Africa. Here, we examined mutations in dihydrofolate reductase, dhfr [chromsosome 4], the dihydropteroate synthase, dhps [chromosome 8] associated with resistance to sulfadoxine-pyrimethamine (SP), and neighboring microsatellites among P. falciparum isolates in Asar village, eastern Sudan. This area lies at the fringes of malaria endemicity, where the remote P. falciparum parasites have some distinct genetic characteristics. Overall, 89% (84/94) of the examined isolates carried double mutations at dhfr (N51I and S108N), but the 59R and I164L mutations were not seen. Similarly, the majority, 43% (35/81) of the isolates carried double mutations at dhps (437G, 540E). Analysis of neighboring microsatellites revealed one major dhfr haplotype with mutations (51I, 108N) and one dhps haplotype with mutations (436S, 437G, 540E). These haplotypes differ from the major ones thought to drive resistance to SP across Africa. The resistant haplotypes of dhfr and dhps, in Asar, share some microsatellites with the wild genotypes suggesting that they were generated locally. Among isolates successfully examined, 40% shared identical haplotypes of the 2 loci, comprising a dominant resistant lineage. Undoubtedly, this lineage plays an important role in clinical failure to SP in this area.

  • 2.
    Ankarklev, Johan
    et al.
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Lebbad, Marianne
    Einarsson, Elin
    Franzen, Oscar
    Ahola, Harri
    Troell, Karin
    Svard, Staffan G.
    A novel high-resolution multilocus sequence typing of Giardia intestinalis Assemblage A isolates reveals zoonotic transmission, clonal outbreaks and recombination2018In: Infection, Genetics and Evolution, ISSN 1567-1348, E-ISSN 1567-7257, Vol. 60, p. 7-16Article in journal (Refereed)
    Abstract [en]

    Molecular epidemiology and genotyping studies of the parasitic protozoan Giardia intestinalis have proven difficult due to multiple factors, such as low discriminatory power in the commonly used genotyping loci, which has hampered molecular analyses of outbreak sources, zoonotic transmission and virulence types. Here we have focused on assemblage A Giardia and developed a high-resolution assemblage-specific multilocus sequence typing (MLST) method. Analyses of sequenced G. intestinalis assemblage A genomes from different sub-assemblages identified a set of six genetic loci with high genetic variability. DNA samples from both humans (n = 44) and animals (n = 18) that harbored Giardia assemblage A infections, were PCR amplified (557-700 bp products) and sequenced at the six novel genetic loci. Bioinformatic analyses showed five to ten-fold higher levels of polymorphic sites than what was previously found among assemblage A samples using the classic genotyping loci. Phylogenetically, a division of two major clusters in assemblage A became apparent, separating samples of human and animal origin. A subset of human samples (n = 9) from a documented Giardia outbreak in a Swedish day-care center, showed full complementarity at nine genetic loci (the six new and the standard BG, TPI and GDH loci), strongly suggesting one source of infection. Furthermore, three samples of human origin displayed MLST profiles that were phylogenetically more closely related to MLST profiles from animal derived samples, suggesting zoonotic transmission. These new genotyping loci enabled us to detect events of recombination between different assemblage A isolates but also between assemblage A and E isolates. In summary, we present a novel and expanded MLST strategy with significantly improved sensitivity for molecular analyses of virulence types, zoonotic potential and source tracking for assemblage A Giardia.

  • 3.
    Ankarklev, Johan
    et al.
    Stockholm Univ, Dept Mol Biosci, SE-10691 Stockholm, Sweden.
    Lebbad, Marianne
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology.
    Einarsson, Elin
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology.
    Franzen, Oscar
    Karolinska Inst, Integrated Cardio Metab Ctr, Novum, Box 285, SE-14157 Stockholm, Sweden.
    Ahola, Harri
    Natl Vet Inst, Dept Microbiol, SE-75189 Uppsala, Sweden.
    Troell, Karin
    Natl Vet Inst, Dept Microbiol, SE-75189 Uppsala, Sweden.
    Svärd, Staffan
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Microbiology.
    A novel high-resolution multilocus sequence typing of Giardia intestinalis Assemblage A isolates reveals zoonotic transmission, clonal outbreaks and recombination2018In: Infection, Genetics and Evolution, ISSN 1567-1348, E-ISSN 1567-7257, Vol. 60, p. 7-16Article in journal (Refereed)
    Abstract [en]

    Molecular epidemiology and genotyping studies of the parasitic protozoan Giardia intestinalis have proven difficult due to multiple factors, such as low discriminatory power in the commonly used genotyping loci, which has hampered molecular analyses of outbreak sources, zoonotic transmission and virulence types. Here we have focused on assemblage A Giardia and developed a high-resolution assemblage-specific multilocus sequence typing (MLST) method. Analyses of sequenced G. intestinalis assemblage A genomes from different sub-assemblages identified a set of six genetic loci with high genetic variability. DNA samples from both humans (n = 44) and animals (n = 18) that harbored Giardia assemblage A infections, were PCR amplified (557-700 bp products) and sequenced at the six novel genetic loci. Bioinformatic analyses showed five to ten-fold higher levels of polymorphic sites than what was previously found among assemblage A samples using the classic genotyping loci. Phylogenetically, a division of two major clusters in assemblage A became apparent, separating samples of human and animal origin. A subset of human samples (n = 9) from a documented Giardia outbreak in a Swedish day-care center, showed full complementarity at nine genetic loci (the six new and the standard BG, TPI and GDH loci), strongly suggesting one source of infection. Furthermore, three samples of human origin displayed MLST profiles that were phylogenetically more closely related to MLST profiles from animal derived samples, suggesting zoonotic transmission. These new genotyping loci enabled us to detect events of recombination between different assemblage A isolates but also between assemblage A and E isolates. In summary, we present a novel and expanded MLST strategy with significantly improved sensitivity for molecular analyses of virulence types, zoonotic potential and source tracking for assemblage A Giardia.

  • 4.
    Baroni de Moraes, Marcia Terezinha
    et al.
    Oswaldo Cruz Fdn FIOCRUZ, Brazil.
    Olivares Olivares, Alberto Ignacio
    Univ Fed Roraima, Brazil; Oswaldo Cruz Fdn FIOCRUZ, Brazil.
    Fialho, Alexandre Madi
    Oswaldo Cruz Fdn FIOCRUZ, Brazil.
    Malta, Fabio Correia
    Oswaldo Cruz Fdn FIOCRUZ, Brazil.
    da Silva e Mouta Junior, Sergio
    Oswaldo Cruz Fdn FIOCRUZ, Brazil.
    Bispo, Romanul de Souza
    Univ Fed Roraima, Brazil.
    Velloso, Alvaro Jorge
    Oswaldo Cruz Fdn FIOCRUZ, Brazil; Oswaldo Cruz Fdn FIOCRUZ, Brazil.
    Alves Leitao, Gabriel Azevedo
    Oswaldo Cruz Fdn FIOCRUZ, Brazil.
    Cantelli, Carina Pacheco
    Oswaldo Cruz Fdn FIOCRUZ, Brazil; Oswaldo Cruz Fdn FIOCRUZ, Brazil; Oswaldo Cruz Fdn FIOCRUZ, Brazil.
    Nordgren, Johan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Svensson, Lennart
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Miagostovich, Marize Pereira
    Oswaldo Cruz Fdn FIOCRUZ, Brazil.
    Gagliardi Leite, Jose Paulo
    Oswaldo Cruz Fdn FIOCRUZ, Brazil.
    Phenotyping of Lewis and secretor HBGA from saliva and detection of new FUT2 gene SNPs from young children from the Amazon presenting acute gastroenteritis and respiratory infection2019In: Infection, Genetics and Evolution, ISSN 1567-1348, E-ISSN 1567-7257, Vol. 70, p. 61-66Article in journal (Refereed)
    Abstract [en]

    The Histo-blood group antigens (HBGA) are host genetic factors associated with susceptibility to rotavirus (RV) and human norovirus (HuNoV), the major etiological agents of viral acute gastroenteritis (AGE) worldwide. The FUT2 gene expressing the alpha-1, 2-L- fucosyltransferase enzyme is important for gut HBGA expression, and also provides a composition of the phenotypic profile achieved through mutations occurring in populations with different evolutionary histories; as such, it can be considered a genetic population marker. In this study, Lewis and secretor HBGA phenotyping was performed using 352 saliva samples collected from children between three months and five years old born in the Amazon (Brazil, Venezuela and English Guyana) presenting AGE or acute respiratory infection (ARI), the latter considered as control samples. The total of children phenotyped as secretors was 323, corresponding to 91.80%. From these, 207 (58.80%) had a Le (a + b +) profile. The HBGA profiles were equally found in children with AGE as well as with ARI. The rs1047781 of the FUT2 gene was not detected in DNA from saliva cells with a Le (a + b +) profile. However, mutations not yet described in the FUT2 gene were observed: missense 325A amp;gt; T, 501C amp;gt; T, 585C amp;gt; T, 855A amp;gt; T and missense substitutions 327C amp;gt; T [S (Ser) amp;gt; C (Cys)], 446 T amp;gt; C [L(Leu) amp;gt; P(Pro)], 723C amp;gt; A [N(Asn) amp;gt; K(Lys)], 724A amp;gt; T [I(Ile) amp;gt; F(Phe)], 736C amp;gt; A [H(His) amp;gt; N(Asn)]. The SNP distribution in the FUT2 gene of the analyzed samples was very similar to that described in Asian populations, including indigenous tribes.

  • 5.
    Bucardo, Filemon
    et al.
    National Autonomous University of Leon, Nicaragua.
    Nordgren, Johan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Impact of vaccination on the molecular epidemiology and evolution of group A rotaviruses in Latin America and factors affecting vaccine efficacy2015In: Infection, Genetics and Evolution, ISSN 1567-1348, E-ISSN 1567-7257, Vol. 34, p. 106-113Article, review/survey (Refereed)
    Abstract [en]

    Despite high rotavirus (RV) vaccine coverage (similar to 83%) and good effectiveness (similar to 77%) against RV-diarrhea hospitalization, RV is still contributing to the burden of diarrhea that persists in hospital settings in several Latin American countries, where RV vaccination is being implemented. Due to the extensive genomic and antigenic diversity, among co-circulating human RV, a major concern has been that the introduction of RV vaccination could exert selection pressure leading to higher prevalence of strains not included in the vaccines and/or emergence of new strains, thus, reducing the efficacy of vaccination. Here we review the molecular epidemiology of RV in Latin America and explore issues of RV evolution and selection in light of vaccination. We further explore etiologies behind the large burden of diarrhea remaining after vaccination in some countries and discuss plausible reasons for vaccine failures. (C) 2015 Elsevier B.V. All rights reserved.

  • 6.
    Bucardo, Filemon
    et al.
    National Autonomous University of Nicaragua, Nicaragua.
    Reyes, Yaoska
    National Autonomous University of Nicaragua, Nicaragua.
    Becker-Dreps, Sylvia
    University of N Carolina, NC USA.
    Bowman, Natalie
    University of N Carolina, NC USA.
    Gruber, Joann F.
    University of N Carolina, NC USA.
    Vinje, Jan
    National Centre Immunizat and Resp Disease, GA USA.
    Espinoza, Felix
    National Autonomous University of Nicaragua, Nicaragua.
    Paniagua, Margarita
    National Autonomous University of Nicaragua, Nicaragua.
    Balmaseda, Angel
    Minist Heatlh, Nicaragua.
    Svensson, Lennart
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Nordgren, Johan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Pediatric norovirus GII.4 infections in Nicaragua, 1999-20152017In: Infection, Genetics and Evolution, ISSN 1567-1348, E-ISSN 1567-7257, Vol. 55, p. 305-312Article in journal (Refereed)
    Abstract [en]

    Objectives: Investigate clinical and epidemiological factors of pediatric GII.4 norovirus infections in children with acute gastroenteritis (AGE) in Nicaragua between 1999 and 2015. Methods: We retrospectively analyzed laboratory and epidemiologic data from 1,790 children amp;lt;= 7 years with AGE from 6 hospitals in Nicaragua (n = 538), and 3 community clinics (n = 919) and households (n = 333) in Leon, between 1999 and 2015. Moreover, asymptomatic children from community clinics (n = 162) and households (n = 105) were enrolled. Norovirus was detected by real-time PCR and genotyped by sequencing the N-terminal and shell region of the capsid gene. Results: Norovirus was found in 19% (n = 338) and 12% (n = 32) of children with and without AGE, respectively. In total, 20 genotypes including a tentatively new genotype were detected. Among children with AGE, the most common genotypes were GII.4 (53%), GII.14 (7%), GII.3 (6%) and GI.3 (6%). In contrast, only one (1.4%) GII.4 was found in asymptomatic children. The prevalence of GII.4 infections was significantly higher in children between 7 and 12 months of age. The prevalence of GII.4 was lowest in households (38%), followed by community clinics (50%) and hospitals (75%). Several different GII.4 variants were detected and their emergence followed the global temporal trend. Conclusions: Overall our study found the predominance of pediatric GII.4 norovirus infections in Nicaragua mostly occurring in children between 7 and 12 months of age, implicating GII.4 as the main norovirus vaccine target.

  • 7.
    Bucardo, Filemon
    et al.
    University of Leon, Nicaragua .
    Rippinger, Christine M.
    NIAID, USA .
    Svensson, Lennart
    Linköping University, Department of Clinical and Experimental Medicine, Molecular Virology. Linköping University, Faculty of Health Sciences.
    Patton, John T.
    NIAID, USA .
    Vaccine-derived NSP2 segment in rotaviruses from vaccinated children with gastroenteritis in Nicaragua2012In: Infection, Genetics and Evolution, ISSN 1567-1348, E-ISSN 1567-7257, Vol. 12, no 6, p. 1282-1294Article in journal (Refereed)
    Abstract [en]

    Rotavirus (RV) vaccination programs have been established in several countries using the human-attenuated G1P[8] monovalent vaccine Rotarix (TM) (GlaxoSmithKline) and/or the human-bovine reassortant G1, G2, G3, G4, P[8] pentavalent vaccine Rotaleq (TM) (Merck). The efficacy of both vaccines is high (similar to 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 (11G1P[8], 1G3P[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 G1 P[8] viruses and the single G3P[8] virus had genome constellations typical of human G1 P[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.

  • 8.
    Caccio, Simone M.
    et al.
    Ist Super Sanita, Dept Infect Dis, Viale Regina Elena 299, I-00161 Rome, Italy.
    Lalle, Marco
    Ist Super Sanita, Dept Infect Dis, Viale Regina Elena 299, I-00161 Rome, Italy.
    Svärd, Staffan
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Microbiology.
    Host specificity in the Giardia duodenalis species complex2018In: Infection, Genetics and Evolution, ISSN 1567-1348, E-ISSN 1567-7257, Vol. 66, p. 335-345Article, review/survey (Refereed)
    Abstract [en]

    Giardia duodenalis is a unicellular flagellated parasite that infects the gastrointestinal tract of a wide range of mammalian species, including humans. Investigations of protein and DNA polymorphisms revealed that G. duodenalis should be considered as a species complex, whose members, despite being morphologically indistinguishable, can be classified into eight groups, or Assemblages, separated by large genetic distances. Assemblages display various degree of host specificity, with Assemblages A and B occurring in humans and many other hosts, Assemblage C and D in canids, Assemblage E in hoofed animals, Assemblage F in cats, Assemblage G in rodents, and Assemblage H in pinnipeds. The factors determining host specificity are only partially understood, and clearly involve both the host and the parasite. Here, we review the results of in vitro and in vivo experiments, and clinical observations to highlight relevant biological and genetic differences between Assemblages, with a focus on human infection.

  • 9. Cho-Ngwa, Fidelis
    et al.
    Zhu, Xiang
    Metuge, Jonathan A
    Daggfeldt, Annika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Grönvik, Kjell-Olov
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Orlando, Ron
    Atwood, James A
    Titanji, Vincent P
    Identification of in vivo released products of Onchocerca with diagnostic potential, and characterization of a dominant member, the OV1CF intermediate filament2011In: Infection, Genetics and Evolution, ISSN 1567-1348, E-ISSN 1567-7257, Vol. 11, no 4, p. 778-783Article in journal (Refereed)
    Abstract [en]

    A sensitive and specific test for the routine diagnosis of active Onchocerca infection is currently lacking. A major drawback in the development of such a test has been the paucity of knowledge of suitable parasite antigens that can serve as targets in antigen-detection assays. In the present investigation, we employed mass spectrometry, bioinformatics and molecular techniques to identify and characterize several potentially diagnostic Onchocerca antigens in the in vivo nodular fluid, which is being investigated for the first time. The majority of the 27 identified antigens lacked a secretory signal. One of them, also identified and characterized in greater detail with the aid of previously developed monoclonal antibodies (Mabs), was a dominant circulating cytoplasmic intermediate filament protein, previously identified and named, OV1CF. Although OV1CF lacks a secretory signal in its amino acid sequence and is not detected in the pure 42h in vitro released products, it is easily detected in the in vivo nodular fluid. We conclude that these in vivo released products offer promise as diagnostics markers in onchocerciasis.

  • 10.
    Costa, Tiago R. D.
    et al.
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology). Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR).
    Amer, Ayad A. A.
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology). Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR).
    Fällman, Maria
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR).
    Fahlgren, Anna
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR).
    Francis, Matthew
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology). Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR).
    Coiled-coils in the YopD translocator family: A predicted structure unique to the YopD N-terminus contributes to full virulence of Yersinia pseudotuberculosis2012In: Infection, Genetics and Evolution, ISSN 1567-1348, E-ISSN 1567-7257, Vol. 12, no 8, p. 1729-1742Article in journal (Refereed)
    Abstract [en]

    Pathogenic Yersinia all harbor a virulence plasmid-encoded Ysc–Yop T3SS. In this system, translocator function is performed by the hydrophobic proteins YopB and YopD. With the goal to better understand how YopD orchestrates yop-regulatory control, translocon pore formation and Yop effector translocation, we performed an in silico prediction of coiled-coil motifs in YopD and YopD-like sequences from other bacteria. Of interest was a predicted N-terminal coiled-coil that occurred solely in Yersinia YopD sequences. To investigate if this unique feature was biologically relevant, two in cis point mutations were generated with a view to disrupting this putative structure. Both mutants maintained full T3SS function in vitro in terms of environmental control of Yops synthesis and secretion, effector toxin translocation and evasion of phagocytosis and killing by cultured immune cells. However, these same mutants were attenuated for virulence in a murine oral-infection model. The cause of this tardy disease progression is unclear. However, these data indicate that any structural flaw in this element unique to the N-terminus will subtly compromise an aspect of YopD biology. Sub-optimal T3SSs are then formed that are unable to fortify Yersinia against attack by the host innate and adaptive immune response.

  • 11. Courtin, David
    et al.
    Milet, Jacqueline
    Bertin, Gwladys
    Vafa, Manijeh
    Stockholm University, Faculty of Science, The Wenner-Gren Institute , Immunology.
    Sarr, Jean Birame
    Watier, Laurence
    Deloron, Philippe
    Troye-Blomberg, Marita
    Stockholm University, Faculty of Science, The Wenner-Gren Institute , Immunology.
    Garcia, André
    Migot-Nabias, Florence
    G6PD A-variant influences the antibody responses to Plasmodium falciparum MSP2.2011In: Infection, Genetics and Evolution, ISSN 1567-1348, E-ISSN 1567-7257, Vol. 11, no 6, p. 1287-1292Article in journal (Refereed)
    Abstract [en]

    High antibody levels directed to Plasmodium falciparum merozoite surface proteins (MSP), including MSP2, as well as genetically related red blood cell defects, have previously been found to be associated with protection against malaria. Here, our main objective was to study the changes in MSP2-specific total IgG, IgG1 and IgG3 responses during a malaria transmission season in order to assess the impact of sickle-cell, α(+)-thalassemia and G6PD variants on antibody kinetics. Repeated parasitological assessments of a cohort of children were conducted during an 8-month period. Antibody responses to recombinant MSP2/3D7 and MSP2/FC27 proteins were measured at the beginning and at the end of transmission season. We found that (i) the period of last Plasmodium falciparum infection during the transmission season was associated with IgG3 anti-MSP2 change. Compared to the IgG3 levels of children infected in January 2003 (end of transmission season), the IgG3 level of children decreased with the length of the period without infection, (ii) G6PD A- carriers had a lower increase of IgG3 levels to MSP2/FC27 and MSP2/3D7 during the transmission season than the noncarriers. This latter finding is suggestive of qualitative and/or quantitative reduction of exposure to malarial antigens related to this genetic variant, leading to weaker stimulation of specific antibody responses. We speculate that cell-mediated immune activity may explain the clinical protection afforded by this genetic trait.

  • 12. Gebieluca Dabul, Andrei Nicoli
    et al.
    Avaca-Crusca, Juliana Sposto
    Navais, Roberto Barranco
    São Carlos Institute of Physics, University of São Paulo, São Carlos, SP, Brazil.
    Merlo, Thaís Panhan
    Van Tyne, Daria
    Gilmore, Michael S.
    Baratella da Cunha Camargo, Ilana Lopes
    Molecular basis for the emergence of a new hospital endemic tigecycline-resistant Enterococcus faecalis ST103 lineage2019In: Infection, Genetics and Evolution, ISSN 1567-1348, E-ISSN 1567-7257, Vol. 67, p. 23-32Article in journal (Refereed)
    Abstract [en]

    Enterococcus faecalis are a major cause of nosocomial infection worldwide, and the spread of vancomycin resistant strains (VRE) limits treatment options. Tigecycline-resistant VRE began to be isolated from inpatients at a Brazilian hospital within months following the addition of tigecycline to the hospital formulary. This was found to be the result of a spread of an ST103 E. faecalis clone. Our objective was to identify the basis for tigecycline resistance in this lineage. The genomes of two closely related tigecycline-susceptible (MIC = 0.06 mg/L), and three representative tigecycline-resistant (MIC = 1 mg/L) ST103 isolates were sequenced and compared. Further, efforts were undertaken to recapitulate the emergence of resistant strains in vitro. The specific mutations identified in clinical isolates in several cases were within the same genes identified in laboratory-evolved strains. The contribution of various polymorphisms to the resistance phenotype was assessed by trans-complementation of the wild type or mutant alleles, by testing for differences in mRNA abundance, and/or by examining the phenotype of transposon insertion mutants. Among tigecycline-resistant clinical isolates, five genes contained non-synonymous mutations, including two genes known to be related to enterococcal tigecycline resistance (tetM and rpsJ). Finally, within the in vitro-selected resistant variants, mutation in the gene for a MarR-family response regulator was associated with tigecycline resistance. This study shows that E. faecalis mutates to attain tigecycline resistance through the complex interplay of multiple mechanisms, along multiple evolutionary trajectories.

  • 13. Giha, Hayder A
    et al.
    ElGhazali, Gehad
    Nasr, Amre
    Stockholm University, Faculty of Science, The Wenner-Gren Institute , Immunology.
    Iriemenam, Nnaemeka C
    Stockholm University, Faculty of Science, The Wenner-Gren Institute , Immunology.
    Berzins, Klavs
    Stockholm University, Faculty of Science, The Wenner-Gren Institute , Immunology.
    Troye-Blomberg, Marita
    Stockholm University, Faculty of Science, The Wenner-Gren Institute , Physiology.
    Theander, Thor G
    Arnot, David
    Clustering of malaria treatment failure (TF) in Daraweesh: hints for host genetic susceptibility to TF with emphasis on immune-modulating SNPs2010In: Infection, Genetics and Evolution, ISSN 1567-1348, E-ISSN 1567-7257, Vol. 10, no 4, p. 481-6Article in journal (Refereed)
    Abstract [en]

    In malaria, drug resistance and treatment failure (TF) are not synonymous, although are escalating together. Over 9 years of surveillances for malaria morbidity and TF in Daraweesh village in eastern Sudan (1991-2004), 136 donors (15-78 years) from 43 households, treated for 278 malaria episodes and had experienced 46 incident of TF, were included in this study. Blood obtained from the donors in 2005, was used for measurement of IgG subclasses against Pf332-C231 antigen and GM/KM allotyping and for genotyping of the donors for; FcgammaRIIA 131 (HH, RH, RR), CRP 286 (C

  • 14. Giha, Hayder A
    et al.
    Nasr, Amre
    Stockholm University, Faculty of Science, The Wenner-Gren Institute , Immunology.
    Iriemenam, Nnaemeka C
    Stockholm University, Faculty of Science, The Wenner-Gren Institute , Immunology.
    Troye-Blomberg, Marita
    Stockholm University, Faculty of Science, The Wenner-Gren Institute , Immunology.
    Berzins, Klavs
    Stockholm University, Faculty of Science, The Wenner-Gren Institute , Immunology.
    Pandey, Janardan P
    Elghazali, Gehad
    Associations of multi-locus polymorphisms in an immune network with susceptibility to uncomplicated Plasmodium falciparum malaria in Daraweesh village, Eastern Sudan2011In: Infection, Genetics and Evolution, ISSN 1567-1348, E-ISSN 1567-7257, Vol. 11, no 7, p. 1674-1681Article in journal (Refereed)
    Abstract [en]

    Susceptibility to uncomplicated malaria (UM), as to other forms of the disease, is genetically determined. Over 9-years of clinical and parasitological follow up of inhabitants of Daraweesh, in Eastern Sudan, the relative susceptibility to UM was estimated in terms of number of episodes experienced by each individual. Previously, we reported that the levels of IgG2 and IgG3 to Pf332-C231 malaria antigen are negatively correlated with number of malaria episodes. In addition, four molecular markers for malaria susceptibility (CRP -286, GM/KM haplotypes, FcγRIIa131 and HbAS) were tested. In this study, the above data were combined and reanalysed. The CRP -286A allele and GM 1,17 5,13,14,6 phenotype were previously found to be associated with increased susceptibility to malaria; however, individuals have both polymorphism together were not more susceptible to UM than the non-carriers of the same double polymorphism. The FcγRIIa-RR131 and HbAA genotypes taken individually or as double polymorphism were not associated with malaria susceptibility; however, their combination with any or both of the former polymorphisms was mostly associated with increased susceptibility to malaria. None of the four markers were associated with the levels of IgG2 and IgG3 against Pf332-C231. In conclusion, while our data support the polygenic nature of susceptibility to UM and highlighted the role of immune markers polymorphisms, the combinations of these markers were not predictable, i.e. the combination of the susceptibility markers will not necessarily render the carriers more susceptible to UM.

  • 15.
    Israelsson, Elisabeth
    et al.
    Stockholm University, Faculty of Science, The Wenner-Gren Institute , Immunology.
    Maiga, Bakary
    Kearsley, Susannah
    Dolo, Amagana
    Homann, Manijeh Vafa
    Doumbo, Ogobara K
    Troye-Blomberg, Marita
    Stockholm University, Faculty of Science, The Wenner-Gren Institute , Immunology.
    Tornvall, Per
    Berzins, Klavs
    Stockholm University, Faculty of Science, The Wenner-Gren Institute , Immunology.
    Cytokine gene haplotypes with a potential effect on susceptibility to malaria in sympatric ethnic groups in Mali2011In: Infection, Genetics and Evolution, ISSN 1567-1348, E-ISSN 1567-7257, Vol. 11, no 7, p. 1608-1615Article in journal (Refereed)
    Abstract [en]

    Cytokines are important players in the immune responses, and an unbalance in pro- and anti-inflammatory cytokine responses may affect parasitemia and pathology in a Plasmodium falciparum infection. Polymorphisms in cytokine genes may affect not only the levels of the protein, but many down-stream functions, such as production of C-reactive protein and immunoglobulin isotype switching. Susceptibility to malaria has been shown to differ between individuals with different genetic backgrounds, as indicated by studies in Fulani and non-Fulani ethnic groups. The aim of this study was to investigate possible interethnic differences in totally twelve single nucleotide polymorphisms (SNPs) in the genes encoding the cytokines IL-1β, IL-6, IL-10 and TNF. These SNPs are present in the promoter region of the genes, and have previously been associated with cytokine expression and with disease outcome in malaria. The results from the present study suggest that the Fulani ethnic group has a more pro-inflammatory response, due to high frequencies of high-producing alleles of IL1β and low-producing alleles of IL10. IL-6 could potentially also contribute to the relatively lower susceptibility to malaria in the Fulani ethnic group, whereas the TNF polymorphisms analysed in this study rather seem to associate with the severity of the infection and not the susceptibility for the infection itself. We therefore suggest that the polymorphisms analysed in this study all show a potential to influence the relatively lower susceptibility to malaria seen in the Fulani ethnic group as compared to the other sympatric ethnic groups.

  • 16. Johansson, Patrik
    et al.
    Olsson, Gert E.
    Low, Hwee-Teng
    Bucht, Göran
    Ahlm, Clas
    Juto, Per
    Elgh, Fredrik
    Örebro University, School of Health and Medical Sciences.
    Puumala hantavirus genetic variability in an endemic region (Northern Sweden)2008In: Infection, Genetics and Evolution, ISSN 1567-1348, E-ISSN 1567-7257, Vol. 8, no 3, p. 286-296Article in journal (Refereed)
    Abstract [en]

    Puumala hantavirus (PUUV), naturally harboured and shed by bank voles (Myodes [Clethrionomys] glareolus), is the etiological agent to nephropathia epidemica (NE), a mild haemorrhagic fever with renal syndrome. Both host and virus are found throughout much of the European continent and in northern Sweden NE is the second most prevalent serious febrile viral infection after influenza. The reliability of diagnostics by PCR depends on genetic variability for the detection of viral nucleic acids in unknown samples. In the present study we evaluated the genetic variability of PUUV isolated from bank voles in an area of northern Sweden highly endemic for NE. Genetic variability among bank voles was also investigated to evaluate co-evolutionary patterns. We found that the viral sequence appeared stable across the 80 km study region, with the exception of the southernmost sampling site, which differed from its nearest neighbour by 7%, despite a geographical separation of only 10 km. The southernmost sampling site demonstrated a higher degree of genetic similarity to PUUV previously isolated 100 km south thereof; two locations appear to constitute a separate PUUV phylogenetic branch. In contrast to the viral genome, no phylogenetic variance was observed in the bank vole mtDNA in this study. Previous studies have shown that as a result of terrestrial mammals' postglacial re-colonization routes, bank voles and associated PUUV of a southern and a northern lineage established a dichotomous contact zone across the Scandinavian peninsula approximately 100-150km south of the present study sites. Our observations reveal evolutionary divergence of PUUV that has led to dissimilarities within the restricted geographical scale of the northern host re-colonization route as well. These results suggest either a static situation in which PUUV strains are regionally well adapted, or an ongoing process in which strains of PUUV circulate on a geographical scale not yet reliably described. (c) 2008 Elsevier B.V. All rights reserved.

  • 17.
    Johansson, Patrik
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology. Chemical, Biological and Radiological Defence, Defence Medical and Environmental Research Institute, DSO National Laboratories, 20 Science Park Drive, Singapore 118230, Singapore; CBRN Defence and Security, Swedish Defence Research Agency, SE-901 82 Umeå, Sweden.
    Olsson, Gert E
    Department of Virology, Swedish Institute for Infectious Disease Control, SE-171 82 Solna, Sweden; CBRN Defence and Security, Swedish Defence Research Agency, SE-901 82 Umeå, Sweden; Wildlife, Fish and Environmental Studies, Swedish University of Agricultural Sciences, SE-901 83 Umeå, Sweden.
    Low, Hwee-Teng
    Bucht, Göran
    CBRN Defence and Security, Swedish Defence Research Agency, SE-901 82 Umeå, Sweden.
    Ahlm, Clas
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Juto, Per
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Elgh, Fredrik
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology. Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Biomedical Laboratory Science. Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Puumala hantavirus genetic variability in an endemic region (Northern Sweden)2008In: Infection, Genetics and Evolution, ISSN 1567-1348, E-ISSN 1567-7257, Vol. 8, no 3, p. 286-296Article in journal (Refereed)
    Abstract [en]

    Puumala hantavirus (PUUV), naturally harboured and shed by bank voles (Myodes [Clethrionomys] glareolus), is the etiological agent to nephropathia epidemica (NE), a mild haemorrhagic fever with renal syndrome. Both host and virus are found throughout much of the European continent and in northern Sweden NE is the second most prevalent serious febrile viral infection after influenza. The reliability of diagnostics by PCR depends on genetic variability for the detection of viral nucleic acids in unknown samples. In the present study we evaluated the genetic variability of PUUV isolated from bank voles in an area of northern Sweden highly endemic for NE. Genetic variability among bank voles was also investigated to evaluate co-evolutionary patterns. We found that the viral sequence appeared stable across the 80km study region, with the exception of the southernmost sampling site, which differed from its nearest neighbour by 7%, despite a geographical separation of only 10km. The southernmost sampling site demonstrated a higher degree of genetic similarity to PUUV previously isolated 100km south thereof; two locations appear to constitute a separate PUUV phylogenetic branch. In contrast to the viral genome, no phylogenetic variance was observed in the bank vole mtDNA in this study. Previous studies have shown that as a result of terrestrial mammals' postglacial re-colonization routes, bank voles and associated PUUV of a southern and a northern lineage established a dichotomous contact zone across the Scandinavian peninsula approximately 100-150km south of the present study sites. Our observations reveal evolutionary divergence of PUUV that has led to dissimilarities within the restricted geographical scale of the northern host re-colonization route as well. These results suggest either a static situation in which PUUV strains are regionally well adapted, or an ongoing process in which strains of PUUV circulate on a geographical scale not yet reliably described.

  • 18.
    Karlsson, Anneli
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Ryberg, Anna
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences.
    Nosouhi Dehnoei, Marjan
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences.
    Borch, Kurt
    Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Östergötland.
    Monstein, Hans-Jürg
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Diagnostics, Department of Clinical Microbiology.
    Variation in number of cagA EPIYA-C phosphorylation motifs between cultured Helicobacter pylori and biopsy strain DNA2012In: Infection, Genetics and Evolution, ISSN 1567-1348, E-ISSN 1567-7257, Vol. 12, no 1, p. 175-179Article in journal (Refereed)
    Abstract [en]

    The Helicobacter pylori cagA gene encodes a cytotoxin which is activated by phosphorylation after entering the host epithelial cell. Phosphorylation occurs on specific tyrosine residues within EPIYA motifs in the variable 3'-region. Four different cagA EPIYA motifs have been defined according to the surrounding amino acid sequence; EPIYA-A, -B, -C and -D. Commonly, EPIYA-A and -B are followed by one or more EPIYA-C or -D motif. Due to observed discrepancies in cagA genotypes in cultured H. pylori and the corresponding DNA extracts it has been suggested that genotyping assays preferentially should be performed directly on DNA isolated from biopsy specimens. Gastric biopsies randomly selected from a Swedish cohort were homogenised and used for both direct DNA isolation and for H. pylori specific culturing and subsequent DNA isolation. In 123 of 153 biopsy specimens, the cagA EPIYA genotypes were in agreement with the corresponding cultured H. pylori strains. A higher proportion of mixed cagA EPIYA genotypes were found in the remaining 30 biopsy specimens. Cloning and sequencing of selected cagA EPIYA amplicons revealed variations in number of cagA EPIYA-C motifs in the mixed amplicons. The study demonstrates that culturing of H. pylori introduces a bias in the number of EPIYA-C motif. Consistent with other H. pylori virulence genotyping studies, we suggest that cagA EPIYA analysis should be performed using total DNA isolated from biopsy specimens.

  • 19.
    Ling, Jiaxin
    et al.
    Univ Helsinki, Med, Dept Virol, Helsinki, Finland..
    Smura, Teemu
    Univ Helsinki, Med, Dept Virol, Helsinki, Finland..
    Tamarit, Daniel
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular Evolution. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Huitu, Otso
    Nat Resources Inst Finland, Forest & Anim Ecol, Tampere, Finland..
    Voutilainen, Liina
    Univ Helsinki, Med, Dept Virol, Helsinki, Finland.;Nat Resources Inst Finland, Forest & Anim Ecol, Helsinki, Finland..
    Henttonen, Heikki
    Nat Resources Inst Finland, Forest & Anim Ecol, Helsinki, Finland..
    Vaheri, Antti
    Univ Helsinki, Med, Dept Virol, Helsinki, Finland..
    Vapalahti, Olli
    Univ Helsinki, Med, Dept Virol, Helsinki, Finland.;Univ Helsinki, Dept Vet Biosci, Helsinki, Finland.;Univ Helsinki, Helsinki Univ Hosp, Helsinki, Finland..
    Sironen, Tarja
    Univ Helsinki, Med, Dept Virol, Helsinki, Finland.;Univ Helsinki, Dept Vet Biosci, Helsinki, Finland..
    Evolution and postglacial colonization of Seewis hantavirus with Sorex araneus in Finland2018In: Infection, Genetics and Evolution, ISSN 1567-1348, E-ISSN 1567-7257, Vol. 57, p. 88-97Article in journal (Refereed)
    Abstract [en]

    Hantaviruses have co-existed with their hosts for millions of years. Seewis virus (SWSV), a soricomorph-borne hantavirus, is widespread in Eurasia, ranging from Central Siberia to Western Europe. To gain insight into the phylogeography and evolutionary history of SWSV in Finland, lung tissue samples of 225 common shrews (Sorex araneus) trapped from different parts of Finland were screened for the presence of SWSV RNA. Forty-two of the samples were positive. Partial small (S), medium (M) and large (L) segments of the virus were sequenced, and analyzed together with all SWSV sequences available in Genbank. The phylogenetic analysis of the partial S-segment sequences suggested that all Finnish SWSV strains shared their most recent common ancestor with the Eastern European strains, while the L-segment suggested multiple introductions. The difference between the Land S-segment phylogenies implied that reassortment events play a role in the evolution of SWSV. Of the Finnish strains, variants from Eastern Finland occupied the root position in the phylogeny, and had the highest genetic diversity, supporting the hypothesis that SWSV reached Finland first form the east. During the spread in Finland, the virus has formed three separate lineages, identified here by correlation analysis of genetic versus geographic distance combined with median-joining network analysis. These results support the hypothesis that Finnish SWSV recolonized Finland with its host, the common shrew, from east after the last ice age 12,000-8000 years ago, and then subsequently spread along emerging land bridges towards west or north with the migration and population expansion of its host.

  • 20.
    Lytsy, Birgitta
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine, Clinical Bacteriology.
    Engstrand, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Gustafsson, Åke
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infection medicine.
    Kaden, Rene
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine, Clinical Bacteriology.
    Time to review the gold standard for genotyping vancomycin-resistant enterococci in epidemiology: Comparing whole-genome sequencing with PFGE and MLST in three suspected outbreaks in Sweden during 2013–20152017In: Infection, Genetics and Evolution, ISSN 1567-1348, E-ISSN 1567-7257, Vol. 54, p. 74-80Article in journal (Refereed)
    Abstract [en]

    Vancomycin-resistant enterococci (VRE) are a challenge to the health-care system regarding transmission rate and treatment of infections. VRE outbreaks have to be controlled from the first cases which means that appropriate and sensitive genotyping methods are needed.

    The aim of this study was to investigate the applicability of whole genome sequencing based analysis compared to Pulsed-Field Gel Electrophoresis (PFGE) and Multi-Locus Sequence Typing (MLST) in epidemiological investigations as well as the development of a user friendly method for daily laboratory use.

    Out of 14,000 VRE - screening samples, a total of 60 isolates positive for either vanA or vanB gene were isolated of which 38 were from patients with epidemiological links from three suspected outbreaks at Uppsala University Hospital. The isolates were genotypically characterised with PFGE, MLST, and WGS based core genome Average Nucleotide Identity analysis (cgANI). PFGE was compared to WGS and MLST regarding reliability, resolution, and applicability capacity.

    The PFGE analysis of the 38 isolates confirmed the epidemiological investigation that three outbreaks had occurred but gave an unclear picture for the largest cluster. The WGS analysis could clearly distinguish six ANI clusters for those 38 isolates.

    As result of the comparison of the investigated methods, we recommend WGS-ANI analysis for epidemiological issues with VRE. The recommended threshold for Enterococcus faecium VRE outbreak strain delineation with core genome based ANI is 98.5%.

    All referred sequences of this study are available from the NCBI BioProject number PRJNA301929.

  • 21.
    Matussek, Andreas
    et al.
    County Hospital Ryhov, Sweden.
    Dienus, Olaf
    County Hospital Ryhov, Sweden.
    Djeneba, Ouermi
    University of Ouagadougou, Burkina Faso.
    Simpore, Jacques
    University of Ouagadougou, Burkina Faso.
    Nitiema, Leon
    University of Ouagadougou, Burkina Faso.
    Nordgren, Johan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Molecular characterization and genetic susceptibility of sapovirus in children with diarrhea in Burkina Faso2015In: Infection, Genetics and Evolution, ISSN 1567-1348, E-ISSN 1567-7257, Vol. 32, p. 396-400Article in journal (Refereed)
    Abstract [en]

    Sapoviruses (Says) are a common cause of gastroenteritis in children. In sub-Saharan Africa, there is a scarcity of information regarding SaV as an etiological agent of diarrhea. Here, we investigated the prevalence, molecular characterization and clinico-epidemiological features of SaV infections in children less than 5 years of age with diarrhea in Burkina Faso. We further investigated the role of type 1 histo blood group antigens as susceptibility factors. In total, 309 fecal and 208 saliva samples from diarrheal children in Ouagadougou, Burkina Faso, were collected between May 2009 and March 2010. Say was detected using real-time PCR, and genogrouped/genotyped by PCR or sequencing. Saliva samples were ABO, Lewis and secretor phenotyped using in house ELISA assays. We found a high prevalence (18%) and large genetic diversity with all 4 human genogroups, and 9 genotypes/genoclusters circulating during the study period. The SaV infections were generally associated with milder symptoms, and neither ABH, Lewis or secretor phenotypes affected susceptibility to Say infections. (C) 2015 Published by Elsevier B.V.

  • 22. Morris, Ulrika
    et al.
    Xu, Weiping
    Msellem, Mwinyi I
    Schwartz, Alanna
    Abass, Ali
    Shakely, Delér
    Cook, Jackie
    Bhattarai, Achuyt
    Petzold, Max
    Greenhouse, Bryan
    Ali, Abdullah S
    Björkman, Anders
    Fröberg, Gabrielle
    Mårtensson, Andreas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD).
    Characterising temporal trends in asymptomatic Plasmodium infections and transporter polymorphisms during transition from high to low transmission in Zanzibar, 2005-2013.2015In: Infection, Genetics and Evolution, ISSN 1567-1348, E-ISSN 1567-7257, Vol. 33, p. 110-117Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Improved understanding of the asymptomatic malaria parasite reservoir is a prerequisite to pursue malaria elimination efforts. We therefore characterised temporal trends and transporter polymorphisms in asymptomatic Plasmodium infections during the transition from high to low transmission in Zanzibar.

    METHODS: Healthy individuals participating in cross-sectional surveys conducted 2005-2013 were screened for asymptomatic malaria by PCR. Complexity/diversity of infection and transporter polymorphisms were assessed in Plasmodium falciparum positive samples. Symptomatic samples were included for comparison of polymorphisms in 2013.

    RESULTS: PCR-determined parasite prevalence declined from 21.1% (CI95% 17.4-24.9) to 2.3% (CI95% 1.7-2.9) from 2005 to 2013. P. falciparum remained the predominant species; prevalence was highest in children and young adults aged 5-25years. Parasite densities and complexity of infection, but not population genetic diversity of P. falciparum, decreased from 2005-2009. pfcrt 76T (99.2-64.7%, p<0.001) and pfmdr1 86Y frequencies (89.4-66.7%, p=0.03) decreased over time. Pfmdr1 (a.a.86,184,1246) YYY and YYD haplotypes were more frequent in asymptomatic than symptomatic infections in 2013 (p<0.001).

    CONCLUSIONS: There is a declining, albeit persistent, reservoir of parasites present at low-densities in asymptomatic individuals in Zanzibar. This study revealed important characteristics of the remaining parasite population, including intriguing temporal trends in molecular markers associated with antimalarial resistance, which need to be further investigated.

  • 23.
    Nordgren, Johan
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Molecular Virology. Linköping University, Faculty of Health Sciences.
    Juste O Bonkoungou, Isidore
    Laboratoire National de Santé Publique du Burkina Faso, Ouagadougou, Burkina Faso, Laboratoire de Biologie Moléculaire, d’Epidémiologie et Surveillance des Bactéries et Virus Transmissibles par les Aliments, CRSBAN/UFR-SVT, Université de Ouagadougou, Ouagadougou, Burkina Faso.
    Nitiema, Leon W.
    Centre de Recherche Biomoléculaire Pietro Annigoni, Saint Camille CERBA/LABIOGENE, Université de Ouagadougou, Ouagadougou, Burkina Faso, Centre de Recherche en Sciences Biologiques, Alimentaires et Nutritionnelles (CRSBAN), Université de Ouagadougou, Ouagadougou, Burkina Faso.
    Sharma, Sumit
    Linköping University, Department of Clinical and Experimental Medicine, Molecular Virology. Linköping University, Faculty of Health Sciences.
    Ouermi, Djeneba
    Centre de Recherche Biomoléculaire Pietro Annigoni, Saint Camille CERBA/LABIOGENE, Université de Ouagadougou, Ouagadougou, Burkina Faso.
    Simpore, Jacques
    Centre de Recherche Biomoléculaire Pietro Annigoni, Saint Camille CERBA/LABIOGENE, Université de Ouagadougou, Ouagadougou, Burkina Faso.
    Barro, Nicolas
    Laboratoire de Biologie Moléculaire, d’Epidémiologie et Surveillance des Bactéries et Virus Transmissibles par les Aliments, CRSBAN/UFR-SVT, Université de Ouagadougou, Ouagadougou, Burkina Faso.
    Svensson, Lennart
    Linköping University, Department of Clinical and Experimental Medicine, Molecular Virology. Linköping University, Faculty of Health Sciences.
    Rotavirus in diarrheal children in rural Burkina Faso: High prevalence of genotype G6P[6]2012In: Infection, Genetics and Evolution, ISSN 1567-1348, E-ISSN 1567-7257, Vol. 12, no 8, p. 1892-1898Article in journal (Refereed)
    Abstract [en]

    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. less thanbrgreater than less thanbrgreater thanIn 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. less thanbrgreater than less thanbrgreater thanNotably, 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 andlt; 0.05). less thanbrgreater than less thanbrgreater thanTo 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.

  • 24.
    Skar, H.
    et al.
    Department of Virology, Swedish Institute for Infectious Disease Control, SE-17182 Solna, Sweden, Department of Microbiology Tumor and Cell Biology, Karolinska Institute, SE-17177 Stockholm, Sweden, Theoretical Biology and Biophysics, Group T-10, Los Alamos National Laboratory, MS K710, Los Alamos, NM 87545, United States.
    Sylvan, S.
    Regional Center for Infectious Disease Control and Prevention, Dag Hammarskjölds väg 17, SE-751 85 Uppsala, Sweden.
    Hansson, H.-B.
    Regional Center for Infectious Disease Control and Prevention, University Hospital MAS, SE-20502 Malmö, Sweden.
    Gustavsson, Olle
    Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Microbiology.
    Boman, H.
    Department of Communicable Diseases Control, Sundsvall Hospital, SE-851 86 Sundsvall, Sweden.
    Albert, J.
    Department of Virology, Swedish Institute for Infectious Disease Control, SE-17182 Solna, Sweden, Department of Microbiology Tumor and Cell Biology, Karolinska Institute, SE-17177 Stockholm, Sweden.
    Leitner, T.
    Theoretical Biology and Biophysics, Group T-10, Los Alamos National Laboratory, MS K710, Los Alamos, NM 87545, United States.
    Multiple HIV-1 introductions into the Swedish intravenous drug user population2008In: Infection, Genetics and Evolution, ISSN 1567-1348, E-ISSN 1567-7257, Vol. 8, no 5, p. 545-552Article in journal (Refereed)
    Abstract [en]

    In 2001, an increase of HIV-1 diagnoses among intravenous drug users (IVDU) was reported in Sweden. In nearby countries, Finland, Russia and the Baltic states, recent outbreaks had been described. Since there was a concern that these outbreaks would carry over to Sweden a study was initiated to determine the factors leading to the Swedish increase of HIV-1 diagnosed IVDUs. HIV-1 env V3 sequences were obtained from 97 patients enrolled in ongoing epidemiological studies encompassing the years 1987-2004 with a focus on 2001-2002. The sequences were used for maximum likelihood and Bayesian inference of the molecular epidemiology. Among the virus spreading in 2001-2002, we found that four different subtypes/CRFs were present in the Swedish IVDU population (A, B, CRF01_AE and CRF06_cpx). Subtype B constituted 85% of the infections, established by 12 independent introductions into the IVDU population. The worrisome increase in 2001 was mainly not a result of import of the outbreaks in nearby countries, but rather a higher detection rate of secondary cases due to efficient epidemiological tracing of the generally slow spread of established forms of subtype B in the IVDU community. However, a few of the non-subtype B cases were linked to the outbreaks in Finland, Estonia and Latvia. Because HIV-1 outbreaks can easily be exported from one country to another amongst IVDUs, this prompts continued surveillance in the Baltic Sea Region.

  • 25.
    Tkachev, Sergey E.
    et al.
    Inst Chem Biol & Fundamental Med SB RAS, Novosibirsk, Russia..
    Chicherina, Galina S.
    Inst Systemat & Ecol Anim SB RAS, Novosibirsk, Russia..
    Golovljova, Irina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Inst Chem Biol & Fundamental Med SB RAS, Novosibirsk, Russia.;Natl Inst Hlth Dev, Tallinn, Estonia.
    Belokopytova, Polina S.
    Inst Chem Biol & Fundamental Med SB RAS, Novosibirsk, Russia..
    Tikunov, Artem Yu.
    Inst Chem Biol & Fundamental Med SB RAS, Novosibirsk, Russia..
    Zadora, Oksana V.
    Inst Systemat & Ecol Anim SB RAS, Novosibirsk, Russia..
    Glupov, Victor V.
    Inst Systemat & Ecol Anim SB RAS, Novosibirsk, Russia..
    Tikunova, Nina V.
    Inst Chem Biol & Fundamental Med SB RAS, Novosibirsk, Russia..
    New genetic lineage within the Siberian subtype of tick-borne encephalitis virus found in Western Siberia, Russia2017In: Infection, Genetics and Evolution, ISSN 1567-1348, E-ISSN 1567-7257, Vol. 56, p. 36-43Article in journal (Refereed)
    Abstract [en]

    Tick-borne encephalitis virus (TBEV), a member of the Flaviviridae family, is a causative agent of a severe neurological disease. There are three main TBEV subtypes: the European (TBEV-Eu), Far Eastern (TBEV-FE), and Siberian (TBEV-Sib). Currently, three lineages within TBEV-Sib have been recorded. In this study, the genetic and biological characteristics of a new original strain, TBEV-2871, isolated in the Novosibirsk province of Western Siberia, Russia were investigated. The strain has low neuroinvasiveness in mice. Phylogenetic analysis demonstrated that TBEV-2871 belongs to TBEV-Sib, but does not cluster with any of the TBEV-Sib lineages. The TBEV-2871 strain has 88-89% nucleotide sequence identity with the other TBEV-Sib strains, 84-86% nucleotide sequence identity with the TBEV-FE and TBEV-Eu subtypes and is genetically close to the subtype division border. The TBEV-2871 polyprotein sequence includes 43 unique amino acid substitutions, 30 of which are recorded at positions that are conserved among all TBEV subtypes. Strain TBEV-2871 and two similar but not identical isolates found in Kemerovo province, Western Siberia are separated into a new lineage tentatively named Obskaya after the name of Ob riber, in the vicinity of which the TBEV-2871 was first found. A molecular evolution investigation demonstrated that within TBEV-Sib, the Obskaya lineage likely separated 1535 years ago, which is even earlier than the Baltic lineage.

  • 26. Wille, Michelle
    et al.
    Avril, Alexis
    Tolf, Conny
    Schager, Anna
    Larsson, Sara
    Borg, Olivia
    Olsen, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Waldenström, Jonas
    Temporal dynamics, diversity, and interplay in three components of the virodiversity of a Mallard population: Influenza A virus, avian paramyxovirus and avian coronavirus2015In: Infection, Genetics and Evolution, ISSN 1567-1348, E-ISSN 1567-7257, Vol. 29, p. 129-137Article in journal (Refereed)
    Abstract [en]

    Multiple infections, or simultaneous infection of a host with multiple parasites, are the rule rather than the exception. Interactions between co-occurring pathogens in a population may be mutualistic, competitive or facilitative. For some pathogen combinations, these interrelated effects will have epidemiological consequences; however this is as yet poorly incorporated into practical disease ecology. For example, screening of Mallards for influenza A viruses (IAV) have repeatedly revealed high prevalence and large subtype diversity in the Northern Hemisphere. Other studies have identified avian paramyxovirus type 1 (APMV-1) and coronaviruses (CoVs) in Mallards, but without making inferences on the larger viral assemblage. In this study we followed 144 wild Mallards across an autumn season in a natural stopover site and constructed infection histories of IAV, APMV-1 and CoV. There was a high prevalence of IAV, comprising of 27 subtype combinations, while APMV-1 had a comparatively low prevalence (with a peak of 2%) and limited strain variation, similar to previous findings. Avian CoVs were common, with prevalence up to 12%, and sequence analysis identified different putative genetic lineages. An investigation of the dynamics of co-infections revealed a synergistic effect between CoV and IAV, whereby CoV prevalence was higher given that the birds were co-infected with IAV. There were no interactive effects between IAV and APMV-1. Disease dynamics are the result of an interplay between parasites, host immune responses, and resources; and is imperative that we begin to include all factors to better understand infectious disease risk.

  • 27.
    Wille, Michelle
    et al.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Biology and Environmental Science.
    Avril, Alexis
    Linnaeus University, Faculty of Health and Life Sciences, Department of Biology and Environmental Science. CIRAD, F-34398 Montpellier, France.
    Tolf, Conny
    Linnaeus University, Faculty of Health and Life Sciences, Department of Biology and Environmental Science.
    Schager, Anna
    Linnaeus University, Faculty of Health and Life Sciences, Department of Biology and Environmental Science.
    Larsson, Sara
    Linnaeus University, Faculty of Health and Life Sciences, Department of Biology and Environmental Science.
    Borg, Olivia
    Linnaeus University, Faculty of Health and Life Sciences, Department of Biology and Environmental Science.
    Olsen, Björn
    Uppsala Univ.
    Waldenström, Jonas
    Linnaeus University, Faculty of Health and Life Sciences, Department of Biology and Environmental Science.
    Temporal dynamics, diversity, and interplay in three components of the virodiversity of a Mallard population: Influenza A virus, avian paramyxovirus and avian coronavirus2015In: Infection, Genetics and Evolution, ISSN 1567-1348, E-ISSN 1567-7257, Vol. 29, p. 129-137Article in journal (Refereed)
    Abstract [en]

    Multiple infections, or simultaneous infection of a host with multiple parasites, are the rule rather than the exception. Interactions between co-occurring pathogens in a population may be mutualistic, competitive or facilitative. For some pathogen combinations, these interrelated effects will have epidemiological consequences; however this is as yet poorly incorporated into practical disease ecology. For example, screening of Mallards for influenza A viruses (IAV) have repeatedly revealed high prevalence and large subtype diversity in the Northern Hemisphere. Other studies have identified avian paramyxovirus type 1 (APMV-1) and coronaviruses (CoVs) in Mallards, but without making inferences on the larger viral assemblage. In this study we followed 144 wild Mallards across an autumn season in a natural stopover site and constructed infection histories of IAV, APMV-1 and CoV. There was a high prevalence of IAV, comprising of 27 subtype combinations, while APMV-1 had a comparatively low prevalence (with a peak of 2%) and limited strain variation, similar to previous findings. Avian CoVs were common, with prevalence up to 12%, and sequence analysis identified different putative genetic lineages. An investigation of the dynamics of co-infections revealed a synergistic effect between CoV and IAV, whereby Coy prevalence was higher given that the birds were co-infected with IAV. There were no interactive effects between IAV and APMV-1. Disease dynamics are the result of an interplay between parasites, host immune responses, and resources; and is imperative that we begin to include all factors to better understand infectious disease risk. (C) 2014 Elsevier B.V. All rights reserved.

  • 28.
    Wille, Michelle
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Lindqvist, Kristine
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Muradrasoli, Shaman
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Department of Laboratory Medicine, Division of Clinical Microbiology, Karolinska Institute, Karolinska University Hospital, SE-14186 Huddinge, Sweden.
    Olsen, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Järhult, Josef D.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Urbanization and the dynamics of RNA viruses in Mallards (Anas platyrhynchos)2017In: Infection, Genetics and Evolution, ISSN 1567-1348, E-ISSN 1567-7257, Vol. 51, p. 89-97Article in journal (Refereed)
    Abstract [en]

    Urbanization is intensifying worldwide, and affects the epidemiology of infectious diseases. However, the effect of urbanization on natural host-pathogen systems remains poorly understood. Urban ducks occupy an interesting niche in that they directly interact with both humans and wild migratory birds, and either directly or indirectly with food production birds. Here we have collected samples from Mallards (Anas platyrhynchos) residing in a pond in central Uppsala, Sweden, from January 2013 to January 2014. This artificial pond is kept ice-free during the winter months, and is a popular location where the ducks are fed, resulting in a resident population of ducks year-round. Nine hundred and seventy seven (977) fecal samples were screened for RNA viruses including: influenza A virus (IAV), avian paramyxovirus 1, avian coronavirus (CoV), and avian astrovirus (AstroV). This intra-annual dataset illustrates that these RNA viruses exhibit similar annual patterns to IAV, suggesting similar ecological factors are at play. Furthermore, in comparison to wild ducks, autumnal prevalence of IAV and CoV are lower in this urban population. We also demonstrate that AstroV might be a larger burden to urban ducks than IAV, and should be better assessed to demonstrate the degree to which wild birds contribute to the epidemiology of these viruses. The presence of economically relevant viruses in urban Mallards highlights the importance of elucidating the ecology of wildlife pathogens in urban environments, which will become increasingly important for managing disease risks to wildlife, food production animals, and humans.

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