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  • 1.
    Abbara, Aula
    et al.
    Imperial College, London, United Kingdom.
    Almalla, Mohamed
    American University of Beirut, Beirut, Lebanon.
    AlMasri, Ibrahim
    O'Brien Institute for Public Health, Cumming School of Medicine, University of Calgary, Calgary, Canada.
    AlKabbani, Hussam
    Department of Health and Nutrition Al-Ameen for Humanitarian Support, Gaziantep, Turkey.
    Karah, Nabil
    Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS). Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR). Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    El-Amin, Wael
    King's College Hospital London, United Arab Emirates.
    Rajan, Latha
    Tulane University School of Public Health and Tropical Medicine, Tulane University, LA, New Orleans, United States.
    Rahhal, Ibrahim
    Hand in Hand for Aid and Development, Gaziantep, Turkey.
    Alabbas, Mohammad
    Hand in Hand for Aid and Development, Gaziantep, Turkey.
    Sahloul, Zaher
    Department of Pulmonology and Critical Care, University of Illinois, IL, Chicago, United States.
    Tarakji, Ahmad
    Syrian American Medical Society, Washington DC, United States.
    Sparrow, Annie
    Department of Population Health Sciences and Policy, Icahn School of Medicine at Mount Sinai, New York, United States.
    The challenges of tuberculosis control in protracted conflict: The case of Syria2020In: International Journal of Infectious Diseases, ISSN 1201-9712, E-ISSN 1878-3511, International Journal of Infectious Diseases, ISSN 1201-9712, Vol. 90, p. 53-59Article, review/survey (Refereed)
    Abstract [en]

    Objectives: Syria's protracted conflict has resulted in ideal conditions for the transmission of tuberculosis (TB) and the cultivation of drug-resistant strains. This paper compares TB control in Syria before and after the conflict using available data, examines the barriers posed by protracted conflict and those specific to Syria, and discusses what measures can be taken to address the control of TB in Syria.

    Results: Forced mass displacement and systematic violations of humanitarian law have resulted in overcrowding and the destruction of key infrastructure, leading to an increased risk of both drug-sensitive and resistant TB, while restricting the ability to diagnose, trace contacts, treat, and follow-up. Pre-conflict, TB in Syria was officially reported at 22 per 100 000 population; the official figure for 2017 of 19 per 100 000 is likely a vast underestimate given the challenges and barriers to case detection. Limited diagnostics also affect the diagnosis of multidrug- and rifampicin-resistant TB, reported as comprising 8.8% of new diagnoses in 2017.

    Conclusions: The control of TB in Syria requires a multipronged, tailored, and pragmatic approach to improve timely diagnosis, increase detection, stop transmission, and mitigate the risk of drug resistance. Solutions must also consider vulnerable populations such as imprisoned and besieged communities where the risk of drug resistance is particularly high, and must recognize the limitations of national programming. Strengthening capacity to control TB in Syria with particular attention to these factors will positively impact other parallel conditions; this is key as attention turns to post-conflict reconstruction.

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  • 2.
    Abbara, Aula
    et al.
    Department of Infection, Imperial College, St Marys Hospital, London, United Kingdom; Syria Public Health Network, London, United Kingdom.
    Almhawish, Naser
    Assistance Coordination Unit, Gaziantep, Turkey.
    Aladhan, Ibrahim
    Environmental Protection Agency of Syria, Gaziantep, Turkey.
    Alobaid, Redwan
    Assistance Coordination Unit, Gaziantep, Turkey.
    Karah, Nabil
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Weaponisation of water2022In: The Lancet, ISSN 0140-6736, E-ISSN 1474-547X, Vol. 400, no 10367, p. 1925-1925Article in journal (Refereed)
  • 3. Abbara, Aula
    et al.
    Rawson, Timothy M.
    Karah, Nabil
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS). Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR).
    El-Amin, Wael
    Hatcher, James
    Tajaldin, Bachir
    Dar, Osman
    Dewachi, Omar
    Abu Sitta, Ghassan
    Uhlin, Bernt Eric
    Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR). Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS). Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Sparrow, Annie
    Antimicrobial resistance in the context of the Syrian conflict: Drivers before and after the onset of conflict and key recommendations2018In: International Journal of Infectious Diseases, ISSN 1201-9712, E-ISSN 1878-3511, Vol. 73, p. 1-6Article, review/survey (Refereed)
    Abstract [en]

    Current evidence describing antimicrobial resistance (AMR) in the context of the Syrian conflict is of poor quality and sparse in nature. This paper explores and reports the major drivers of AMR that were present in Syria pre-conflict and those that have emerged since its onset in March 2011. Drivers that existed before the conflict included a lack of enforcement of existing legislation to regulate over-the-counter antibiotics and notification of communicable diseases. This contributed to a number of drivers of AMR after the onset of conflict, and these were also compounded by the exodus of trained staff, the increase in overcrowding and unsanitary conditions, the increase in injuries, and economic sanctions limiting the availability of required laboratory medical materials and equipment. Addressing AMR in this context requires pragmatic, multifaceted action at the local, regional, and international levels to detect and manage potentially high rates of multidrug-resistant infections. Priorities are (1) the development of a competent surveillance system for hospital-acquired infections, (2) antimicrobial stewardship, and (3) the creation of cost-effective and implementable infection control policies. However, it is only by addressing the conflict and immediate cessation of the targeting of health facilities that the rehabilitation of the health system, which is key to addressing AMR in this context, can progress. 

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  • 4.
    Abbara, Aula
    et al.
    Imperial College, London, United Kingdom; Syria Public Health Network, United Kingdom.
    Zakieh, Omar
    Imperial College, London, United Kingdom.
    Rayes, Diana
    Syria Public Health Network, United Kingdom; Johns Hopkins, United States.
    Collin, Simon M.
    Public Health England, United Kingdom.
    Almhawish, Naser
    Assistance Coordination Unit, Turkey.
    Sullivan, Richard
    King's College, London, United Kingdom.
    Aladhan, Ibrahim
    Assistance Coordination Unit, Turkey.
    Tarnas, Maia
    Community Research Initiative, MA, Charlestown, United States.
    Whalen-Browne, Molly
    University of Alberta, Edmonton, Canada.
    Omar, Maryam
    St Bartholomew's Hospital, London, United Kingdom.
    Tarakji, Ahmad
    Syrian American Medical Society, United States.
    Karah, Nabil
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Weaponizing water as an instrument of war in Syria: Impact on diarrhoeal disease in Idlib and Aleppo governorates, 2011–20192021In: International Journal of Infectious Diseases, ISSN 1201-9712, E-ISSN 1878-3511, Vol. 108, p. 202-208Article in journal (Refereed)
    Abstract [en]

    Objectives: Investigate the weaponization of water during the Syrian conflict and the correlation of attacks on water, sanitation, and hygiene (WASH) infrastructure in Idlib and Aleppo governorates with trends in waterborne diseases reported by Early Warning and Response surveillance systems.

    Methods: We reviewed literature and databases to obtain information on attacks on WASH in Aleppo and Idlib governorates between 2011 and 2019. We plotted weekly trends in waterborne diseases from two surveillance systems operational in Aleppo and Idlib governorates between 2015 and early 2020.

    Results: The literature review noted several attacks on water and related infrastructure in both governorates, suggesting that WASH infrastructure was weaponized by state and non-state actors. Most interference with WASH in the Aleppo governorate occurred before 2019 and in the Idlib governorate in the summer of 2020. Other acute diarrhea represented >90% of cases of diarrhea; children under 5 years contributed 50% of cases. There was substantial evidence (p < 0.001) of an overall upward trend in cases of diarrheal disease.

    Conclusions: Though no direct correlation can be drawn between the weaponization of WASH and the burden of waterborne infections due to multiple confounders, this research introduces important concepts on attacks on WASH and their potential impacts on waterborne diseases.

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  • 5.
    Abdelrahim, Nada Abdelghani
    et al.
    Department of Pathology-Medical Microbiology, Faculty of Medicine, University of Medical Sciences and Technology, Khartoum, Sudan.
    Mohamed, Nahla
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Evander, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Ahlm, Clas
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Fadl-Elmula, Imad Mohammed
    Department of Pathology & Clinical Genetics, Al-Neelain University & Assafa Academy, Khartoum, Sudan.
    Viral meningitis in Sudanese children: differentiation, etiology and review of literature2022In: Medicine, ISSN 0025-7974, E-ISSN 1536-5964, Vol. 101, no 46, article id e31588Article, review/survey (Refereed)
    Abstract [en]

    Diagnosis of viral meningitis (VM) is uncommon practice in Sudan and there is no local viral etiological map. We therefore intended to differentiate VM using standardized clinical codes and determine the involvement of herpes simplex virus types-1 and 2 (HSV-1/2), varicella zoster virus, non-polio human enteroviruses (HEVs), and human parechoviruses in meningeal infections in children in Sudan. This is a cross-sectional hospital-based study. Viral meningitis was differentiated in 503 suspected febrile attendee of Omdurman Hospital for Children following the criteria listed in the Clinical Case Definition for Aseptic/Viral Meningitis. Patients were children age 0 to 15 years. Viral nucleic acids (DNA/RNA) were extracted from cerebrospinal fluid (CSF) specimens using QIAamp® UltraSens Virus Technology. Complementary DNA was prepared from viral RNA using GoScriptTM Reverse Transcription System. Viral nucleic acids were amplified and detected using quantitative TaqMan® Real-Time and conventional polymerase chain reactions (PCRs). Hospital diagnosis of VM was assigned to 0%, when clinical codes were applied; we considered 3.2% as having VM among the total study population and as 40% among those with proven infectious meningitis. Two (0.4%) out of total 503 CSF specimens were positive for HSV-1; Ct values were 37.05 and 39.10 and virus copies were 652/PCR run (261 × 103/mL CSF) and 123/PCR run (49.3 × 103/mL CSF), respectively. Other 2 (0.4%) CSF specimens were positive for non-polio HEVs; Ct values were 37.70 and 38.30, and the approximate virus copies were 5E2/PCR run (~2E5/mL CSF) and 2E2/PCR run (~8E4/mL CSF), respectively. No genetic materials were detected for HSV-2, varicella zoster virus, and human parechoviruses. The diagnosis of VM was never assigned by the hospital despite fulfilling the clinical case definition. Virus detection rate was 10% among cases with proven infectious meningitis. Detected viruses were HSV-1 and non-polio HEVs. Positive virus PCRs in CSFs with normal cellular counts were seen.

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  • 6.
    Abdel-Shafi, Seham
    et al.
    Botany and Microbiology Department, Faculty of Science, Zagazig University, Zagazig, Egypt.
    El-Serwy, Heba
    Botany and Microbiology Department, Faculty of Science, Zagazig University, Zagazig, Egypt.
    El-Zawahry, Yehia
    Botany and Microbiology Department, Faculty of Science, Zagazig University, Zagazig, Egypt.
    Zaki, Maysaa
    Clinical Pathology Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt.
    Sitohy, Basel
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology. Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Sitohy, Mahmoud
    Biochemistry Department, Faculty of Agriculture, Zagazig University, Zagazig, Egypt.
    The Association between icaA and icaB Genes, Antibiotic Resistance and Biofilm Formation in Clinical Isolates of Staphylococci spp.2022In: Antibiotics, ISSN 0066-4774, E-ISSN 2079-6382, Vol. 11, no 3, article id 389Article in journal (Refereed)
    Abstract [en]

    Sixty-six (66) Staphylococcus bacterial isolates were withdrawn from separate clinical samples of hospitalized patients with various clinical infections. Conventional bacteriological tests identified the species of all isolates, and standard microbiological techniques differentiated them into CoPS or CoNS. Their biofilm development was followed by an analysis via the MTP (microtiter tissue culture plates) technique, and we then investigated the presence/absence of icaA and icaB, which were qualified in the top-30 potent biofilm-forming isolates. Thirteen isolates (46.7%) showed the presence of one gene, six (20%) isolates exhibited the two genes, while ten (33.3%) had neither of them. The formation of staphylococci biofilms in the absence of ica genes may be related to the presence of other biofilm formation ica-independent mechanisms. CoPS was the most abundant species among the total population. S. aureus was the sole representative of CoPS, while S. epidermidis was the most abundant form of CoNS. Antibiotic resistance was developing against the most frequently used antimicrobial drugs, while vancomycin was the least-resisted drug. The totality of the strong and medium-strength film-forming isolates represented the majority proportion (80%) of the total investigated clinical samples. The biochemical pattern CoPS is associated with antibiotic resistance and biofilm formation and can be an alarming indicator of potential antibiotic resistance.

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  • 7. Abou Fayad, A.
    et al.
    El Diwachi, O.
    Haraoui, L. P.
    Abu Sitta, G.
    Nguyen, V. -K
    Abbara, A.
    Landecker, H.
    Karah, Nabil
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Knapp, C.
    McEvoy, M.
    Zamman, M.
    Higgins, P.
    Matar, G.
    War, antimicrobial resistance, and Acinetobacter baumannii (WAMRA)2020In: International Journal of Infectious Diseases, ISSN 1201-9712, E-ISSN 1878-3511, Vol. 101, p. 87-88Article in journal (Other academic)
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  • 8. Adderley, Jack D.
    et al.
    von Freyend, Simona John
    Jackson, Sarah A.
    Bird, Megan J.
    Burns, Amy L.
    Anar, Burcu
    Metcalf, Tom
    Semblat, Jean-Philippe
    Billker, Oliver
    Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS). Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology). Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire, UK.
    Wilson, Danny W.
    Doerig, Christian
    Analysis of erythrocyte signalling pathways during Plasmodium falciparum infection identifies targets for host-directed antimalarial intervention2020In: Nature Communications, E-ISSN 2041-1723, Vol. 11, no 1, article id 4015Article in journal (Refereed)
    Abstract [en]

    Intracellular pathogens mobilize host signaling pathways of their host cell to promote their own survival. Evidence is emerging that signal transduction elements are activated in a-nucleated erythrocytes in response to infection with malaria parasites, but the extent of this phenomenon remains unknown. Here, we fill this knowledge gap through a comprehensive and dynamic assessment of host erythrocyte signaling during infection with Plasmodium falciparum. We used arrays of 878 antibodies directed against human signaling proteins to interrogate the activation status of host erythrocyte phospho-signaling pathways at three blood stages of parasite asexual development. This analysis reveals a dynamic modulation of many host signalling proteins across parasite development. Here we focus on the hepatocyte growth factor receptor (c-MET) and the MAP kinase pathway component B-Raf, providing a proof of concept that human signaling kinases identified as activated by malaria infection represent attractive targets for antimalarial intervention.

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  • 9. Ades, A. E.
    et al.
    Brickley, Elizabeth B.
    Alexander, Neal
    Brown, David
    Jaenisch, Thomas
    Miranda-Filho, Democrito de Barros
    Pohl, Moritz
    Rosenberger, Kerstin D.
    Soriano-Arandes, Antoni
    Thorne, Claire
    Ximenes, Ricardo Arraes de Alencar
    de Araujo, Thalia Velho Barreto
    Avelino-Silva, Vivian, I
    Bethencourt Castillo, Sarah Esperanza
    Borja Aburto, Victor Hugo
    Brasil, Patricia
    Christie, Celia D. C.
    de Souza, Wayner Vieira
    Gotuzzo, H. Jose Eduardo
    Hoen, Bruno
    Koopmans, Marion
    Martelli, Celina Maria Turchi
    Martins Teixeira, Mauro
    Marques, Ernesto T. A.
    Miranda, Maria Consuelo
    Montarroyos, Ulisses Ramos
    Moreira, Maria Elisabeth
    Morris, J. Glenn
    Rockx, Barry
    Saba Villarroel, Paola Mariela
    Soria Segarra, Carmen
    Tami, Adriana
    Turchi, Marilia Dalva
    Giaquinto, Carlo
    de Lamballerie, Xavier
    Wilder-Smith, Annelies
    Umeå University, Faculty of Medicine, Department of Epidemiology and Global Health.
    Zika virus infection in pregnancy: a protocol for the joint analysis of the prospective cohort studies of the ZIKAlliance, ZikaPLAN and ZIKAction consortia2020In: BMJ Open, E-ISSN 2044-6055, Vol. 10, no 12, article id e035307Article in journal (Refereed)
    Abstract [en]

    Introduction: Zika virus (ZIKV) infection in pregnancy has been associated with microcephaly and severe neurological damage to the fetus. Our aim is to document the risks of adverse pregnancy and birth outcomes and the prevalence of laboratory markers of congenital infection in deliveries to women experiencing ZIKV infection during pregnancy, using data from European Commission-funded prospective cohort studies in 20 centres in 11 countries across Latin America and the Caribbean.

    Methods and analysis: We will carry out a centre-by-centre analysis of the risks of adverse pregnancy and birth outcomes, comparing women with confirmed and suspected ZIKV infection in pregnancy to those with no evidence of infection in pregnancy. We will document the proportion of deliveries in which laboratory markers of congenital infection were present. Finally, we will investigate the associations of trimester of maternal infection in pregnancy, presence or absence of maternal symptoms of acute ZIKV infection and previous flavivirus infections with adverse outcomes and with markers of congenital infection. Centre-specific estimates will be pooled using a two-stage approach.

    Ethics and dissemination: Ethical approval was obtained at each centre. Findings will be presented at international conferences and published in peer-reviewed open access journals and discussed with local public health officials and representatives of the national Ministries of Health, Pan American Health Organization and WHO involved with ZIKV prevention and control activities.

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  • 10. Adler, Sara
    et al.
    Widerström, Micael
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Lindh, Johan
    Lilja, Mikael
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Symptoms and risk factors of Cryptosporidium hominis infection in children: data from a large waterborne outbreak in Sweden2017In: Parasitology Research, ISSN 0932-0113, E-ISSN 1432-1955, Vol. 116, no 10, p. 2613-2618Article in journal (Refereed)
    Abstract [en]

    Cryptosporidium is a major cause of diarrheal disease worldwide. In developing countries, this infection is endemic and in children, associated with growth faltering and cognitive function deficits, with the most severe impact on those aged <2 years. Little has been reported about symptoms and risk factors for children in industrialized countries, although the disease incidence is increasing in such regions. In November 2010, a large waterborne outbreak of C. hominis occurred in the city of Östersund in Sweden. Approximately 27,000 of the 60,000 inhabitants were symptomatic. We aimed to describe duration of symptoms and the risk factors for infection with C. hominis in children aged <15 years in a Western setting. Within 2 months after a boil water advisory, a questionnaire was sent to randomly selected inhabitants of all ages, including 753 children aged <15 years. Those with ≥3 loose stools/day were defined as cases of diarrhoea. The response rate was 70.3%, and 211 children (39.9%) fulfilled the case definition. Mean duration of diarrhoea was 7.5 days (median 6, range 1-80 days). Recurrence, defined as a new episode of diarrhoea after ≥2 days of normal stools, occurred in 52.5% of the cases. Significant risk factors for infection, besides living within the distribution area of the contaminated water plant, included a high level of water consumption, male sex, and a previous history of loose stools. The outbreak was characterized by high attack and recurrence rates, emphasizing the necessity of water surveillance to prevent future outbreaks.

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  • 11. Affognon, H.
    et al.
    Mburu, P.
    Hassan, Osama Ahmed
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Kingori, S.
    Ahlm, C.
    Sang, R.
    Evander, M.
    Sociocultural differences affect Rift Valley fever exposureManuscript (preprint) (Other academic)
  • 12. Affognon, Hippolyte
    et al.
    Mburu, Peter
    Hassan, Osama Ahmed
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Kingori, Sarah
    Ahlm, Clas
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Sang, Rosemary
    Evander, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Ethnic groups' knowledge, attitude and practices and Rift Valley fever exposure in Isiolo County of Kenya2017In: PLoS Neglected Tropical Diseases, ISSN 1935-2727, E-ISSN 1935-2735, Vol. 11, no 3, article id e0005405Article in journal (Refereed)
    Abstract [en]

    Rift Valley fever (RVF) is an emerging mosquito-borne viral hemorrhagic fever in Africa and the Arabian Peninsula, affecting humans and livestock. For spread of infectious diseases, including RVF, knowledge, attitude and practices play an important role, and the understanding of the influence of behavior is crucial to improve prevention and control efforts. The objective of the study was to assess RVF exposure, in a multiethnic region in Kenya known to experience RVF outbreaks, from the behavior perspective. We investigated how communities in Isiolo County, Kenya were affected, in relation to their knowledge, attitude and practices, by the RVF outbreak of 2006/2007. A cross-sectional study was conducted involving 698 households selected randomly from three different ethnic communities. Data were collected using a structured questionnaire regarding knowledge, attitudes and practices that could affect the spread of RVF. In addition, information was collected from the communities regarding the number of humans and livestock affected during the RVF outbreak. This study found that better knowledge about a specific disease does not always translate to better practices to avoid exposure to the disease. However, the high knowledge, attitude and practice score measured as a single index of the Maasai community may explain why they were less affected, compared to other investigated communities (Borana and Turkana), by RVF during the 2006/2007 outbreak. We conclude that RVF exposure in Isiolo County, Kenya during the outbreak was likely determined by the behavioral differences of different resident community groups. We then recommend that strategies to combat RVF should take into consideration behavioral differences among communities.

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  • 13. Afset, J. E.
    et al.
    Larssen, K. W.
    Bergh, K.
    Larkeryd, A.
    Sjodin, A.
    Johansson, Anders
    Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS). Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Bacteriology.
    Forsman, M.
    Phylogeographical pattern of Francisella tularensis in a nationwide outbreak of tularaemia in Norway, 20112015In: Eurosurveillance, ISSN 1025-496X, E-ISSN 1560-7917, Vol. 20, no 19, p. 9-14, article id 21125Article in journal (Refereed)
    Abstract [en]

    In 2011, a nationwide outbreak of tularaemia occurred in Norway with 180 recorded cases. It was associated with the largest peak in lemming density seen in 40 years. Francisella tularensis was isolated from 18 patients. To study the geographical distribution of F. tularensis genotypes in Norway and correlate genotype with epidemiology and clinical presentation, we performed whole genome sequencing of patient isolates. All 18 genomes from the outbreak carried genetic signatures of F. tularensis subsp. holarctica and were assigned to genetic clades using canonical single nucleotide polymorphisms. Ten isolates were assigned to major genetic clade B.6 (subclade B.7), seven to clade B.12, and one to clade B.4. The B.6 subclade B.7 was most common in southern and central Norway, while clade B.12 was evenly distributed between the southern, central and northern parts of the country. There was no association between genotype and clinical presentation of tularaemia, time of year or specimen type. We found extensive sequence similarity with F. tularensis subsp. holarctica genomes from high-endemic tularaemia areas in Sweden. Finding nearly identical genomes across large geographical distances in Norway and Sweden imply a life cycle of the bacterium without replication between the outbreaks and raise new questions about long-range migration mechanisms.

  • 14.
    Agerhäll, Martin
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Henrikson, Martin
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Johansson Söderberg, Jenny
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Sellin, Mats
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Tano, Krister
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Gylfe, Åsa
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Berggren, Diana
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    High prevalence of pharyngeal bacterial pathogens among healthy adolescents and young adults2021In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 129, no 12, p. 711-716Article in journal (Refereed)
    Abstract [en]

    The pharyngeal mucosa can be colonized with bacteria that have potential to cause pharyngotonsillitis. By the use of culturing techniques and PCR, we aimed to assess the prevalence of bacterial pharyngeal pathogens among healthy adolescents and young adults. We performed a cross-sectional study in a community-based cohort of 217 healthy individuals between 16 and 25 years of age. Samples were analyzed for Group A streptococci (GAS), Group C/G streptococci (SDSE), Fusobacterium necrophorum, and Arcanobacterium haemolyticum. Compared to culturing, the PCR method resulted in more frequent detection, albeit in most cases with low levels of DNA, of GAS (20/217 vs. 5/217; p < 0.01) and F. necrophorum (20/217 vs. 8/217; p < 0.01). Culturing and PCR yielded similar rates of SDSE detection (14/217 vs. 12/217; p = 0.73). Arcanobacterium haemolyticum was rarely detected (3/217), and only by PCR. Overall, in 25.3% (55/217) of these healthy adolescents and young adults at least one of these pathogens was detected, a rate that is higher than previously described. Further studies are needed before clinical adoption of PCR-based detection methods for pharyngeal bacterial pathogens, as our findings suggest a high incidence of asymptomatic carriage among adolescents and young adults without throat infections.

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  • 15.
    Ahlm, Clas
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Distribution of puumala virus in Sweden1997Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Puumala virus, belonging to the genus hantavirus, is the causative agent of nephropathia epidemica (NE), a relatively mild form of hemorrhagic fever with renal syndrome. Puumala virus occurs endemically in Central and Northern Europe and Western Russia. In Sweden, NE is reported from the northern and central parts but virtually not at all from the southern part of the country. The bank vole (Clethrionomys glareolus) is the main reservoir of Puumala virus and humans are infected by inhalation of aerosolized animal secreta. In northern Sweden, the density of the bank vole population varies cyclically in intervals of 3-4 years and the incidence of NE shows a covariation.

    The prevalence of serum antibodies to hantaviruses in northern Sweden was studied in a stratified and randomly selected adult population sample comprising 1538 subjects. As expected, the prevalence increased with age. There was no difference between men and women, which was unexpected based on a male:female ratio of > 2:1 in clinical reports. By use of an immunofiuorescent assay, a seroprevalence of 5.4% and by a newly developed enzyme-linked immunosorbent assay (ELISA) with recombinant Puumala virus nucleocapsid protein as antigen, a prevalence of 8.9% was recorded. This is about or more than ten times higher than what would be calculated from clinical reports.

    By use of the ELISA, an occupational risk of acquisition of Puumala virus infection was demonstrated. Serum samples from 910 farmers and 663 referent subjects living in various rural parts of Sweden were tested. Among farmers from the Puumala virus-endemic northern and central parts of the country, the seroprevalence (12.9%) was higher (p=0.01) than in referents (6.8%). In the southern part of Sweden, only 2/459 persons had antibodies. Only a limited number of children with NE had been previously reported. In a separate study, 32 children with Puumala virus infection were identified and the clinical picture of NE in children was found to be similar to that of adult cases.

    Variations in the prevalence of Puumala virus in the bank vole population within an endemic region are not well known. Here, a higher mean rodent density and a higher prevalence of Puumala virus-specific serum antibodies were recorded in the vicinity of households afflicted with NE than in rural control areas. The data indicated that the risk of exposure locally within an endemic region may vary widely and tentatively suggested that a threshold density of bank voles might be necessary to achieve before effective spread of Puumala virus within the rodent population may occur.

    There is no firm evidence of the occurrence of Puumala virus among wild living animals other than rodents. A study of Swedish moose, an animal which is ecologically well characterized, was performed. Convincing evidence of past Puumala virus infection was found in 5/260 moose originating from Puumala virus-endemic areas but in none of 167 animals from nonendemic areas. Based on the low seroprevalence recorded, moose seemed to serve as endstage hosts rather than being active parts of the enzootic circle of transmission.

    In conclusion, the present investigations confirmed that the exposure to Puumala virus is geographically well restricted in Sweden. Seroprevalence studies indicated that only a minor proportion of individuals infected with Puumala virus are clinically reported, with a bias in favour of men. NE was confirmed to occur in children, with a clinical picture similar to that of adults. An occupational risk was defined for acquisition of Puumala virus infection. Studies in rodents suggested that there may be wide local variations within a limited area in the risk of exposure to Puumala virus. The studies validated the usefulness of a newly developed ELISA based on recombinant nucleocapsid peptides of hantaviruses and finally, methodological progress was reached when Puumala virus was, for the first time, successfully isolated from a Scandinavian patient.

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  • 16.
    Ahlm, Clas
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Eliasson, Mats
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Vapalahti, O.
    University of Helsinki and Helsinki University Central Hospital Laboratory, Finland.
    Evander, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Seroprevalence of Sindbis virus and associated risk factors in northern Sweden2014In: Epidemiology and Infection, ISSN 0950-2688, E-ISSN 1469-4409, Vol. 142, no 7, p. 1559-1565Article in journal (Refereed)
    Abstract [en]

    Mosquito-borne Sindbis virus (SINV) cause disease characterized by rash, fever and arthritis which often leads to long-lasting arthralgia. To determine the seroprevalence of SINV and associated risk factors in northern Sweden, a randomly selected population aged between 25 and 74 years were invited to join the MONICA study. Serum from 1611 samples were analysed for specific IgG antibodies. Overall, 2·9% had IgG against SINV. More men (3·7%) than women (2·0%) were SINV seropositive (P = 0·047) and it was more common in subjects with a lower educational level (P = 0·013) and living in small, rural communities (P < 0·001). Seropositivity was associated with higher waist circumference (P = 0·1), elevated diastolic blood pressure (P = 0·037), and history of a previous stroke (P = 0·011). In a multiple logistic regression analysis, adjusting for known risk factors for stroke, seropositivity for SINV was an independent predictor of having had a stroke (odds ratio 4·3, 95% confidence interval 1·4–13·0,P = 0·011).

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  • 17.
    Ahsan, Umaira
    et al.
    Institute of Biomedical and Allied Health Sciences, University of Health Sciences, Lahore, Pakistan; Department of Microbiology, University of Health Sciences, Lahore, Pakistan.
    Mushtaq, Fizza
    Institute of Biomedical and Allied Health Sciences, University of Health Sciences, Lahore, Pakistan.
    Saleem, Sidrah
    Department of Microbiology, University of Health Sciences, Lahore, Pakistan.
    Malik, Abdul
    Institute of Biomedical and Allied Health Sciences, University of Health Sciences, Lahore, Pakistan.
    Sarfaraz, Hira
    Institute of Biomedical and Allied Health Sciences, University of Health Sciences, Lahore, Pakistan.
    Shahzad, Muhammad
    Department of Pharmacology, University of Health Sciences, Lahore, Pakistan.
    Uhlin, Bernt Eric
    Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR). Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Ahmad, Irfan
    Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR). Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Institute of Biomedical and Allied Health Sciences, University of Health Sciences, Lahore, Pakistan.
    Emergence of high colistin resistance in carbapenem resistant Acinetobacter baumannii in Pakistan and its potential management through immunomodulatory effect of an extract from Saussurea lappa2022In: Frontiers in Pharmacology, E-ISSN 1663-9812, Vol. 13, article id 986802Article in journal (Refereed)
    Abstract [en]

    Carbapenem resistant Acinetobacter baumannii has emerged as one of the most difficult to treat nosocomial bacterial infections in recent years. It was one of the major causes of secondary infections in Covid-19 patients in developing countries. The polycationic polypeptide antibiotic colistin is used as a last resort drug to treat carbapenem resistant A. baumannii infections. Therefore, resistance to colistin is considered as a serious medical threat. The purpose of this study was to assess the current status of colistin resistance in Pakistan, a country where carbapenem resistant A. bumannii infections are endemic, to understand the impact of colistin resistance on virulence in mice and to assess alternative strategies to treat such infections. Out of 150 isolates collected from five hospitals in Pakistan during 2019–20, 84% were carbapenem resistant and 7.3% were additionally resistant to colistin. There were two isolates resistant to all tested antibiotics and 83% of colistin resistant isolates were susceptible to only tetracycline family drugs doxycycline and minocycline. Doxycycline exhibited a synergetic bactericidal effect with colistin even in colistin resistant isolates. Exposure of A. baumannii 17978 to sub inhibitory concentrations of colistin identified novel point mutations associated with colistin resistance. Colistin tolerance acquired independent of mutations in lpxA, lpxB, lpxC, lpxD, and pmrAB supressed the proinflammatory immune response in epithelial cells and the virulence in a mouse infection model. Moreover, the oral administration of water extract of Saussuria lappa, although not showing antimicrobial activity against A. baumannii in vitro, lowered the number of colonizing bacteria in liver, spleen and lung of the mouse model and also lowered the levels of neutrophils and interleukin 8 in mice. Our findings suggest that the S. lappa extract exhibits an immunomodulatory effect with potential to reduce and cure systemic infections by both opaque and translucent colony variants of A. baumannii.

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  • 18. Alberione, Maria Pia
    et al.
    Moeller, Rebecca
    Kirui, Jared
    Ginkel, Corinne
    Doepke, Mandy
    Stroeh, Luisa J.
    Machtens, Jan-Philipp
    Pietschmann, Thomas
    Gerold, Gisa
    Umeå University, Faculty of Medicine, Wallenberg Centre for Molecular Medicine at Umeå University (WCMM). Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Section of Virology. Institute for Experimental Virology, TWINCORE, Centre for Experimental and Clinical Infection Research, a joint venture between the Medical School Hannover and the Helmholtz Centre for Infection Research, Hannover, Germany.
    Single-nucleotide variants in human CD81 influence hepatitis C virus infection of hepatoma cells2020In: Medical Microbiology and Immmunology, ISSN 0300-8584, E-ISSN 1432-1831, Vol. 209, no 4, p. 499-514Article in journal (Refereed)
    Abstract [en]

    An estimated number of 71 million people are living with chronic hepatitis C virus (HCV) infection worldwide and 400,000 annual deaths are related to the infection. HCV entry into the hepatocytes is complex and involves several host factors. The tetraspanin human CD81 (hCD81) is one of the four essential entry factors and is composed of one large extracellular loop, one small extracellular loop, four transmembrane domains, one intracellular loop and two intracellular tails. The large extracellular loop interacts with the E2 glycoprotein of HCV. Regions outside the large extracellular loop (backbone) of hCD81 have a critical role in post-binding entry steps and determine susceptibility of hepatocytes to HCV. Here, we investigated the effect of five non-synonymous single-nucleotide variants in the backbone of hCD81 on HCV susceptibility. We generated cell lines that stably express the hCD81 variants and infected the cells using HCV pseudoparticles and cell culture-derived HCV. Our results show that all the tested hCD81 variants support HCV pseudoparticle entry with similar efficiency as wild-type hCD81. In contrast, variants A54V, V211M and M220I are less supportive to cell culture-derived HCV infection. This altered susceptibility is HCV genotype dependent and specifically affected the cell entry step. Our findings identify three hCD81 genetic variants that are impaired in their function as HCV host factors for specific viral genotypes. This study provides additional evidence that genetic host variation contributes to inter-individual differences in HCV infection and outcome.

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  • 19. Albrecht, Letusa
    et al.
    Moll, Kirsten
    Blomqvist, Karin
    Normark, Johan
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Chen, Qijun
    Wahlgren, Mats
    var gene transcription and PfEMP1 expression in the rosetting and cytoadhesive Plasmodium falciparum clone FCR3S1.22011In: Malaria Journal, ISSN 1475-2875, E-ISSN 1475-2875, Vol. 10, article id 17Article in journal (Refereed)
    Abstract [en]

    Background: The pathogenicity of Plasmodium falciparum is in part due to the ability of the parasitized red blood cell (pRBC) to adhere to intra- vascular host cell receptors and serum-proteins. Binding of the pRBC is mediated by Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1), a large multi-variant molecule encoded by a family of approximate to 60 var genes. Methods: The study of var gene transcription in the parasite clone FCR3S1.2 was performed by semi-quantitative PCR and quantitative PCR (qPCR). The expression of the major PfEMP1 in FCR3S1.2 pRBC was analysed with polyclonal sera in rosette disruption assays and immunofluorecence. Results: Transcripts from var1 (FCR3S1.2(var1); IT4var21) and other var genes were detected by semi-quantitative PCR but results from qPCR showed that one var gene transcript dominated over the others (FCR3S1.2var2; IT4var60). Antibodies raised in rats to the recombinant NTS-DBL1a of var2 produced in E. coli completely and dosedependently disrupted rosettes (approximate to 95% at a dilution of 1/5). The sera reacted with the Maurer's clefts in trophozoite stages (IFA) and to the infected erythrocyte surface (FACS) indicating that FCR3S1.2var2 encodes the dominant PfEMP1 expressed in this parasite. Conclusion: The major transcript in the rosetting model parasite FCR3S1.2 is FCR3S1.2var2 (IT4var60). The results suggest that this gene encodes the PfEMP1-species responsible for the rosetting phenotype of this parasite. The activity of previously raised antibodies to the NTS-DBL1a of FCR3S1.2var1 is likely due to cross-reactivity with NTS-DBL1 alpha of the var2 encoded PfEMP1.

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  • 20.
    Ali, Rewaa
    et al.
    Department of Botany, Faculty of Science, Mansoura University, Mansoura, Egypt.
    Khamis, Tarek
    Department of Pharmacology, Faculty of Veterinary Medicine, Zagazig University, Zagazig, Egypt.
    Enan, Gamal
    Department of Botany and Microbiology, Faculty of Sciences, Zagazig University, Zagazig, Egypt.
    El-Didamony, Gamal
    Department of Botany and Microbiology, Faculty of Sciences, Zagazig University, Zagazig, Egypt.
    Sitohy, Basel
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology. Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Abdel-Fattah, Gamal
    Department of Botany, Faculty of Science, Mansoura University, Mansoura, Egypt.
    The Healing Capability of Clove Flower Extract (CFE) in Streptozotocin-Induced (STZ-Induced) Diabetic Rat Wounds Infected with Multidrug Resistant Bacteria2022In: Molecules, ISSN 1431-5157, E-ISSN 1420-3049, Vol. 27, no 7, article id 2270Article in journal (Refereed)
    Abstract [en]

    Treatment of diabetic foot ulcer (DFU) is of great challenge as it is shown to be infected by multidrug resistant bacteria (MDR bacteria). Sixty four bacterial isolates were isolated from DFU cases; antibiotic susceptibility tests were carried out for all of them. One bacterial isolate (number 11) was shown to resist the action of 8 out of 12 antibiotics used and was identified by both a Vitek-2 system and 16S rRNA fingerprints as belonging to Proteus mirabilis, and was designated Proteus mirabilis LC587231 (P. mirabilis). Clove flower extract (CFE) inhibited distinctively the P. mirabilis bacterium obtained. GC-MS spectroscopy showed that this CFE contained nine bioactive compounds. The effect of CFE on wound healing of Type 1 diabetic albino rats (Rattus norvegicus) was studied. The results indicated that topical application of CFE hydrogel improved wound size, wound index, mRNA expression of the wound healing markers (Coli1, MMP9, Fibronectin, PCNA, and TGFβ), growth factor signaling pathways (PPAR-α, PGC1-α, GLP-1, GLPr-1, EGF-β, EGF-βr, VEGF-β, and FGF-β), inflammatory cytokine expression (IL8, TNFα, NFKβ, IL1β, and MCP1), as well as anti-inflammatory cytokines (IL4 & IL10), pro-apoptotic markers (FAS, FAS-L, BAX, BAX/BCL-2, Caspase-3, P53, P38), as well as an antiapoptotic one (BCL2). Furthermore, it improved the wound oxidative state and reduced the wound microbial load, as the cefepime therapy improved the wound healing parameters. Based on the previous notions, it could be concluded that CFE represents a valid antibiotics alternative for DFU therapy since it improves diabetic wound healing and exerts antibacterial activity either in vitro or in vivo.

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  • 21.
    Allwell-Brown, Gbemisola
    et al.
    Department of Women's and Children's Health, International Maternal and Child Health (IMCH), Uppsala University, Uppsala, Sweden.
    Hussain-Alkhateeb, Laith
    Global Health, School of Public Health and Community Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Sewe, Maquins
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Sustainable Health.
    Kitutu, Freddy Eric
    Department of Women's and Children's Health, International Maternal and Child Health (IMCH), Uppsala University, Uppsala, Sweden; Sustainable Pharmaceutical Systems (SPS) Unit, Department of Pharmacy, School of Health Sciences, Makerere University, PO Box 7072, Kampala, Uganda.
    Strömdahl, Susanne
    Section of Infectious Diseases, Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
    Mårtensson, Andreas
    Department of Women's and Children's Health, International Maternal and Child Health (IMCH), Uppsala University, Uppsala, Sweden.
    Johansson, Emily White
    Department of Women's and Children's Health, International Maternal and Child Health (IMCH), Uppsala University, Uppsala, Sweden.
    Determinants of trends in reported antibiotic use among sick children under five years of age across low-income and middle-income countries in 2005–17: A systematic analysis of user characteristics based on 132 national surveys from 73 countries2021In: International Journal of Infectious Diseases, ISSN 1201-9712, E-ISSN 1878-3511, Vol. 108, p. 473-482Article in journal (Refereed)
    Abstract [en]

    Objectives: This study aimed to analyze any reported antibiotic use for children aged <5 years with fever, diarrhea or cough with fast or difficult breathing (outcome) from low-income and middle-income countries (LMICs) during 2005–2017 by user characteristics: rural/urban residence, maternal education, household wealth, and healthcare source visited.

    Methods: Based on 132 demographic and health surveys and multiple indicator cluster surveys from 73 LMICs, the outcome by user characteristics for all country-years was estimated using a hierarchical Bayesian linear regression model.

    Results: Across LMICs during 2005–2017, the greatest relative increases in the outcome occurred in rural areas, poorest quintiles and least educated populations, particularly in low-income countries and South-East Asia. In low-income countries, rural areas had a 72% relative increase from 17.8% (Uncertainty Interval (UI): 5.2%–44.9%) in 2005 to 30.6% (11.7%–62.1%) in 2017, compared to a 29% relative increase in urban areas from 27.1% (8.7%–58.2%) in 2005 to 34.9% (13.3%–67.3%) in 2017. Despite these increases, the outcome was consistently highest in urban areas, wealthiest quintiles, and populations with the highest maternal education.

    Conclusion: These estimates suggest that the increasing reported antibiotic use for sick children aged <5 years in LMICs during 2005–2017 was driven by gains among groups often underserved by formal health services.

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  • 22.
    Almhawish, Naser
    et al.
    Assistance Coordination Unit, Gaziantep, Turkey.
    Karah, Nabil
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Elferruh, Yasir
    Assistance Coordination Unit, Gaziantep, Turkey.
    Aksh, Aya
    Assistance Coordination Unit, Gaziantep, Turkey.
    Abbara, Aula
    Department of Infection, Imperial College, St Mary's Hospital, Praed Street, London, United Kingdom; Syria Public Health Network, London, United Kingdom.
    Protecting healthcare workers in conflict zones during the COVID-19 pandemic: Northwest Syria2021In: Journal of Infection, ISSN 0163-4453, E-ISSN 1532-2742, Vol. 82, no 5, p. 186-230Article in journal (Refereed)
  • 23. Alqahtani, F. Y.
    et al.
    Aleanizy, F. S.
    Mohamed, R. Ali El Hadi
    Alanazi, M. S.
    Mohamed, Nahla
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology. College of Medicine, Princess Nourah bint Abdulrahman University, Riyadh 12484, Saudi Arabia.
    Alrasheed, M. M.
    Abanmy, N.
    Alhawassi, T.
    Prevalence of comorbidities in cases of Middle East respiratory syndrome coronavirus: a retrospective study2019In: Epidemiology and Infection, ISSN 0950-2688, E-ISSN 1469-4409, Vol. 147, article id e35Article in journal (Refereed)
    Abstract [en]

    The Middle East respiratory syndrome coronavirus (MERS-CoV) is a life-threatening respiratory disease with a high case fatality rate; however, its risk factors remain unclear. We aimed to explore the influence of demographic factors, clinical manifestations and underlying comorbidities on mortality in MERS-CoV patients. Retrospective chart reviews were performed to identify all laboratory-confirmed cases of MERS-COV infection in Saudi Arabia that were reported to the Ministry of Health of Saudi Arabia between 23 April 2014 and 7 June 2016. Statistical analyses were conducted to assess the effect of sex, age, clinical presentation and comorbidities on mortality from MERS-CoV. A total of 281 confirmed MERS-CoV cases were identified: 167 (59.4%) patients were male and 55 (20%) died. Mortality predominantly occurred among Saudi nationals and older patients and was significantly associated with respiratory failure and shortness of breath. Of the 281 confirmed cases, 160 (56.9%) involved comorbidities, wherein diabetes mellitus, hypertension, ischemic heart disease, congestive heart failure, end-stage renal disease and chronic kidney disease were significantly associated with mortality from MERS-CoV and two or three comorbidities significantly affected the fatality rates from MERS-CoV. The findings of this study show that old age and the existence of underlying comorbidities significantly increase mortality from MERS-CoV.

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  • 24. Amada, Takako
    et al.
    Yoshimatsu, Kumiko
    Koma, Takaaki
    Shimizu, Kenta
    Gamage, Chandika D.
    Shiokawa, Kanae
    Nishio, Sanae
    Ahlm, Clas
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Arikawa, Jiro
    Development of an immunochromatography strip test based on truncated nucleocapsid antigens of three representative hantaviruses2014In: Virology Journal, E-ISSN 1743-422X, Vol. 11, p. 87-Article in journal (Refereed)
    Abstract [en]

    Background: Hantaviruses are causative agents of hemorrhagic fever with renal syndrome (HFRS) and nephropathia epidemica (NE) in the Old World and hantavirus pulmonary syndrome (HPS) in the New World. There is a need for time-saving diagnostic methods. In the present study, recombinant N antigens were used as antigens in an immunochromatography strip (ICG) test to detect specific IgG antibodies. Methods: The N-terminal 103 amino acids (aa) of Hantaan virus (HTNV), Puumala virus (PUUV) and Andes virus (ANDV) nucleocapsid (N) protein were expressed in E. coli as representative antigens of three groups (HFRS, NE and HPS-causing viruses) of hantavirus. Five different types of ICG test strips, one antigen line on one strip for each of the three selected hantaviruses (HTNV, PUUV and ANDV), three antigen lines on one strip and a mixed antigen line on one strip, were developed and sensitivities were compared. Results: A total of 87 convalescent-phase patient sera, including sera from 35 HFRS patients, 36 NE patients and 16 HPS patients, and 25 sera from healthy seronegative people as negative controls were used to evaluate the ICG test. Sensitivities of the three-line strip and mixed-line strip were similar to those of the single antigen strip (97.2 to 100%). On the other hand, all of the ICG test strips showed high specificities to healthy donors. Conclusion: These results indicated that the ICG test with the three representative antigens is an effective serodiagnostic tool for screening and typing of hantavirus infection in humans.

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  • 25. Amorim, Gisele C
    et al.
    Cisneros, David A.
    Unité de Génétique Moléculaire, Département de MicrobiologieInstitut Pasteur, Paris Cedex 15 France; CNRS, ERL 3526, Paris, France.
    Delepierre, Muriel
    Francetic, Olivera
    Izadi-Pruneyre, Nadia
    ¹H, ¹⁵N and ¹³C resonance assignments of PpdD, a type IV pilin from enterohemorrhagic Escherichia coli2014In: Biomolecular NMR Assignments, ISSN 1874-2718, E-ISSN 1874-270X, Vol. 8, no 1, p. 43-46Article in journal (Refereed)
    Abstract [en]

    Bacterial type 4 pili (T4P) are long flexible fibers involved in adhesion, DNA uptake, phage transduction, aggregation and a flagella-independent movement called "twitching motility". T4P comprise thousands of copies of the major pilin subunit, which is initially inserted in the plasma membrane, processed and assembled into dynamic helical filaments. T4P are crucial for host colonization and virulence of many Gram-negative bacteria. In enterohemorrhagic Escherichia coli the T4P, called hemorrhagic coli pili (HCP) promote cell adhesion, motility, biofilm formation and signaling. To understand the mechanism of HCP assembly and function, we analyzed the structure of the major subunit prepilin peptidase-dependent protein D (PpdD) (also called HcpA), a 15 kDa pilin with two potential disulfide bonds. Here we present the (1)H, (15)N and (13)C backbone and side chain resonance assignments of the C-terminal globular domain of PpdD as a first step to its structural determination.

  • 26.
    Anantharajah, Ahalieyah
    et al.
    Pharmacologie Cellulaire et Moléculaire, Louvain Drug Research Institute, Université Catholique de Louvain, Brussels, Belgium.
    Faure, Emmanuel
    EA7366, Host-Pathogen Translational Research Group, Faculté de Médecine, Université Lille Nord de France, Lille, France.
    Buyck, Julien M.
    Pharmacologie Cellulaire et Moléculaire, Louvain Drug Research Institute, Université Catholique de Louvain, Brussels, Belgium; Focal Area Infection Biology, Biozentrum, University of Basel, Switzerland.
    Sundin, Charlotta
    Umeå University, Faculty of Science and Technology, Department of Chemistry. Creative Antibiotics, Umeå, Sweden .
    Lindmark, Tuulikki
    Creative Antibiotics, Umeå, Sweden; Disruptivematerials, Uppsala, Sweden.
    Mecsas, Joan
    Department of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, MA, United States.
    Yahr, Timothy L.
    Department of Microbiology, University of Iowa, Iowa City, United States.
    Tulkens, Paul M.
    Pharmacologie Cellulaire et Moléculaire, Louvain Drug Research Institute, Université Catholique de Louvain, Brussels, Belgium.
    Mingeot-Leclercq, Marie-Paule
    Pharmacologie Cellulaire et Moléculaire, Louvain Drug Research Institute, Université Catholique de Louvain, Brussels, Belgium.
    Guery, Benoît
    EA7366, Host-Pathogen Translational Research Group, Faculté de Médecine, Université Lille Nord de France, Lille, France.
    Van Bambeke, Françoise
    Pharmacologie Cellulaire et Moléculaire, Louvain Drug Research Institute, Université Catholique de Louvain, Brussels, Belgium.
    Inhibition of the injectisome and flagellar type III secretion systems by INP1855 impairs Pseudomonas aeruginosa pathogenicity and inflammasome activation2016In: Journal of Infectious Diseases, ISSN 0022-1899, E-ISSN 1537-6613, Vol. 214, no 7, p. 1105-1116Article in journal (Refereed)
    Abstract [en]

    With the rise of multidrug resistance, Pseudomonas aeruginosa infections require alternative therapeutics. The injectisome (iT3SS) and flagellar (fT3SS) type III secretion systems are 2 virulence factors associated with poor clinical outcomes. iT3SS translocates toxins, rod, needle, or regulator proteins, and flagellin into the host cell cytoplasm and causes cytotoxicity and NLRC4-dependent inflammasome activation, which induces interleukin 1 beta (IL-1 beta) release and reduces interleukin 17 (IL-17) production and bacterial clearance. fT3SS ensures bacterial motility, attachment to the host cells, and triggers inflammation. INP1855 is an iT3SS inhibitor identified by in vitro screening, using Yersinia pseudotuberculosis. Using a mouse model of P. aeruginosa pulmonary infection, we show that INP1855 improves survival after infection with an iT3SS-positive strain, reduces bacterial pathogenicity and dissemination and IL-1 beta secretion, and increases IL-17 secretion. INP1855 also modified the cytokine balance in mice infected with an iT3SS-negative, fT3SS-positive strain. In vitro, INP1855 impaired iT3SS and fT3SS functionality, as evidenced by a reduction in secretory activity and flagellar motility and an increase in adenosine triphosphate levels. As a result, INP1855 decreased cytotoxicity mediated by toxins and by inflammasome activation induced by both laboratory strains and clinical isolates. We conclude that INP1855 acts by dual inhibition of iT3SS and fT3SS and represents a promising therapeutic approach.

  • 27. Andersen, Petter I.
    et al.
    Krpina, Klara
    Ianevski, Aleksandr
    Shtaida, Nastassia
    Jo, Eunji
    Yang, Jaewon
    Koit, Sandra
    Tenson, Tanel
    Hukkanen, Veijo
    Anthonsen, Marit W.
    Bjoras, Magnar
    Evander, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Section of Virology.
    Windisch, Marc P.
    Zusinaite, Eva
    Kainov, Denis E.
    Novel Antiviral Activities of Obatoclax, Emetine, Niclosamide, Brequinar, and Homoharringtonine2019In: Viruses, E-ISSN 1999-4915, Vol. 11, no 10, article id 964Article in journal (Refereed)
    Abstract [en]

    Viruses are the major causes of acute and chronic infectious diseases in the world. According to the World Health Organization, there is an urgent need for better control of viral diseases. Repurposing existing antiviral agents from one viral disease to another could play a pivotal role in this process. Here, we identified novel activities of obatoclax and emetine against herpes simplex virus type 2 (HSV-2), echovirus 1 (EV1), human metapneumovirus (HMPV) and Rift Valley fever virus (RVFV) in cell cultures. Moreover, we demonstrated novel activities of emetine against influenza A virus (FLUAV), niclosamide against HSV-2, brequinar against human immunodeficiency virus 1 (HIV-1), and homoharringtonine against EV1. Our findings may expand the spectrum of indications of these safe-in-man agents and reinforce the arsenal of available antiviral therapeutics pending the results of further in vitro and in vivo tests.

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  • 28.
    Andersson, Nirina
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology.
    Preuss, Isabella
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology.
    Boman, Jens
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology.
    Nylander, Elisabet
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology.
    Chlamydia Infection Among Digital Daters and Nondigital Daters2019In: Journal of Lower Genital Tract Disease, ISSN 1089-2591, E-ISSN 1526-0976, Vol. 23, no 3, p. 230-234Article in journal (Refereed)
    Abstract [en]

    Objectives: The aim of the study was to investigate whether the use of dating apps is a risk factor for acquiring Chlamydia trachomatis (CT) infections.

    Methods: Patients attending the drop-in facility at the STI clinic at Umea University Hospital between April 2016 and November 2017 were asked to fill in a survey about their sexual preferences and behaviors, including dating app use.

    Results: Of 943 participants, 80 (8.5%) received a CT diagnosis (34 women and 46 men). Dating app users did not seem to have an increased risk of CT infection. Having 3 or more sex partners within the last year was a risk factor for CT only among those not using a dating app. Alcohol use before sex and unprotected sex with a new partner were risk factors for CT infection in the univariate but not in the multivariate analysis.

    Conclusions: Dating app users did not seem to have an increased risk of acquiring CT and for dating app users the seemingly well-established risk factor of having many partners was not valid.

  • 29.
    Andersson Norlén, Elina
    et al.
    Department of Infectious Diseases, Östersund Hospital, Östersund, Sweden.
    Widerström, Micael
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Lindam, Anna
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Olsson, Johanna
    Department of Microbiology, Östersund Hospital, Östersund, Sweden.
    Ryding, Ulf
    Department of Infectious Diseases, Östersund Hospital, Östersund, Sweden.
    Blood cultures with one venipuncture instead of two: a prospective clinical comparative single-center study including patients in the ICU, haematology, and infectious diseases departments2023In: Infectious Diseases, ISSN 2374-4235, E-ISSN 2374-4243, Vol. 55, no 9, p. 591-598Article in journal (Refereed)
    Abstract [en]

    Objectives: Blood culture is a key method for diagnosing bloodstream infections. In this prospective study, we aimed to investigate whether blood cultures collected with the one-puncture method results in fewer contaminants, i.e. microorganisms from the skin or the environment, and the same detection of relevant pathogens compared to the two-puncture method. Further, we aimed to investigate if the time to blood culture positivity could be useful in evaluating contaminants.

    Methods: Patients planned for blood cultures were asked to participate in the study. From each recruited patient, six blood culture bottles were drawn, bottles 1–4 from the first venipuncture and bottles 5–6 from the second venipuncture. Within each patient, bottles 1–4 were compared to bottles 1, 2, 5, and 6 for contaminants and relevant pathogens. A sub-analysis was conducted on patients admitted to the ICU and those in the haematology department. We also assessed time-to-positivity for coagulase-negative staphylococci.

    Results: In the final analysis, 337 episodes from 312 patients were included. Relevant pathogens were identified in 62/337 (18.4%) episodes in both methods. Contaminants were detected in 12 (3.6%) and 19 episodes (5.6%) using the one-puncture and two-puncture method (p =.039), respectively. Corresponding results were observed in the sub-analysis. Notably, relevant coagulase-negative staphylococci demonstrated a shorter time-to-positivity compared to contaminant coagulase-negative staphylococci.

    Conclusion: Blood cultures obtained using the one-puncture method resulted in significantly fewer contaminants and detected relevant pathogens equally to the two-puncture method. Time-to-positivity may be a useful additive indicator for predicting coagulase-negative staphylococci contamination in blood cultures.

  • 30.
    Andersson, T
    et al.
    Department of Mathematics, Stockholm University, Sweden and Swedish Institute for National Food Agency (SLV), Sweden and Communicable Disease Control (SMI), Solna, Sweden.
    Bjelkmar, P
    Swedish Institute for Communicable Disease Control (SMI), Solna, Sweden, and Inera AB, Sweden.
    Hulth, A
    Swedish Institute for Communicable Disease Control (SMI), Solna, Sweden.
    Lindh, J
    Department of Microbiology, Tumour and Cell Biology, Karolinska Institutet, Sweden and Swedish Institute for Communicable Disease Control (SMI), Solna, Sweden.
    Stenmark, Stephan
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases. County Medical Officer, Västerbotten, Sweden.
    Widerström, Micael
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Bacteriology. Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Syndromic surveillance for local outbreak detection and awareness: evaluating outbreak signals of acute gastroenteritis in telephone triage, web-based queries and over-the-counter pharmacy sales2014In: Epidemiology and Infection, ISSN 0950-2688, E-ISSN 1469-4409, Vol. 142, no 2, p. 303-313Article in journal (Refereed)
    Abstract [en]

    For the purpose of developing a national system for outbreak surveillance, local outbreak signals were compared in three sources of syndromic data - telephone triage of acute gastroenteritis, web queries about symptoms of gastrointestinal illness, and over-the-counter (OTC) pharmacy sales of antidiarrhoeal medication. The data sources were compared against nine known waterborne and foodborne outbreaks in Sweden in 2007-2011. Outbreak signals were identified for the four largest outbreaks in the telephone triage data and the two largest outbreaks in the data on OTC sales of antidiarrhoeal medication. No signals could be identified in the data on web queries. The signal magnitude for the fourth largest outbreak indicated a tenfold larger outbreak than officially reported, supporting the use of telephone triage data for situational awareness. For the two largest outbreaks, telephone triage data on adult diarrhoea provided outbreak signals at an early stage, weeks and months in advance, respectively, potentially serving the purpose of early event detection. In conclusion, telephone triage data provided the most promising source for surveillance of point-source outbreaks.

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  • 31.
    Andresen, Liis
    et al.
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS).
    Varik, Vallo
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS). University of Tartu, Institute of Technology, Nooruse 1, 50411 Tartu, Estonia.
    Tozawa, Yuzuru
    Jimmy, Steffi
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS).
    Lindberg, Stina
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Tenson, Tanel
    Hauryliuk, Vasili
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS). University of Tartu, Institute of Technology, Nooruse 1, 50411 Tartu, Estonia.
    Auxotrophy-based High Throughput Screening assay for the identification of Bacillus subtilis stringent response inhibitors2016In: Scientific Reports, E-ISSN 2045-2322, Vol. 6, article id 35824Article in journal (Refereed)
    Abstract [en]

    The stringent response is a central adaptation mechanism that allows bacteria to adjust their growth and metabolism according to environmental conditions. The functionality of the stringent response is crucial for bacterial virulence, survival during host invasion as well as antibiotic resistance and tolerance. Therefore, specific inhibitors of the stringent response hold great promise as molecular tools for disarming and pacifying bacterial pathogens. By taking advantage of the valine amino acid auxotrophy of the Bacillus subtilis stringent response-deficient strain, we have set up a High Throughput Screening assay for the identification of stringent response inhibitors. By screening 17,500 compounds, we have identified a novel class of antibacterials based on the 4-(6-(phenoxy) alkyl)-3,5-dimethyl-1H-pyrazole core. Detailed characterization of the hit compounds as well as two previously identified promising stringent response inhibitors-a ppGpp-mimic nucleotide Relacin and cationic peptide 1018 - showed that neither of the compounds is sufficiently specific, thus motivating future application of our screening assay to larger and more diverse molecular libraries.

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  • 32. Andrii, Dudnyk
    et al.
    Matthew, Burman
    Ludmyla, Kulyk
    Olena, Rzhepishevska
    Umeå University, Faculty of Science and Technology, Department of Chemistry. Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    M/XDR‐TB treatment perspective: how to avoid mountains of pills via digital technologies2018In: Respirology (Carlton South. Print), ISSN 1323-7799, E-ISSN 1440-1843, Vol. 23, no 6, p. 636-637Article in journal (Refereed)
  • 33.
    Angelin, Martin
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Travel – a risk factor for disease and spread of antibiotic resistance2015Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    As international travel is rapidly increasing, more people are being exposed to potentially more antibiotic resistant bacteria, a changed infectious disease epidemiology, and an increased risk of accidents and crime. Research-based advice is needed to adequately inform travellers about these risks. We studied travellers who sought advice from the Travel Medicine Clinic at the Department of Infectious Diseases, Umeå University Hospital, as well as university students from Umeå, Stockholm, and Gothenburg travelling abroad for study, research, and clinical exchange programs.

    From retrospective data at the Travel Medicine Clinic, we found that pre-existing health problems were rare among travellers from Umeå seeking pre- travel health advice and vaccinations. In addition, we found that the travel destination and the sex of the traveller affected vaccination levels. Although hepatitis A is endemic to both Thailand and Turkey, compared to travellers to Thailand few travellers to Turkey visited the clinic for hepatitis A vaccination. The data also revealed that more women than men were vaccinated against Japanese encephalitis despite comparable trips.

    A prospective survey study showed that travellers felt that the pre-travel health advice they received was helpful. Two-thirds of the travellers followed the advice given although they still fell ill to the same extent as those who were not compliant with the advice. Factors outside the control of travellers likely affect the travel-related morbidity. Compared to older travellers, younger travellers were less compliant with advice, fell ill to a greater extent, and took greater risks during travel.

    In a prospective survey study, we found that healthcare students had higher illness rates and risk exposure when abroad compared to students from other disciplines. This difference was mainly due to the fact that healthcare students more often travelled to developing regions during their study period abroad. When abroad, half of all students increased their alcohol consumption and this was linked to an increased risk of theft and higher likelihood of meeting a new sex partner.

    The healthcare students participating in the survey study also submitted stool samples before and after travel. These samples were tested for the presence of antibiotic resistance, both by selective culturing for ESBL-PE (Extended-Spectrum Beta-Lactamase Producing Enterobacteriaceae) as well as by metagenomic sequencing. About one-third (35%) of the students became colonised by ESBL-PE following their study abroad. The strongest risk factor for colonisation was travel destination; for example, 70% of students who had travelled to India became colonised. Antibiotic treatment during travel was also a significant risk factor for colonisation.

    The stool samples from a subset of study subjects were analysed using metagenomic sequencing. From this we learned that although the majority of resistance genes in the gut microbiome remained unchanged following travel, several clinically important resistance genes increased, most prominently genes encoding resistance to sulphonamide, trimethoprim, and beta-lactams. Overall, taxonomic changes associated with travel were small but the proportion of Proteobacteria, which includes several clinically important bacteria (e.g., Enterobacteriaceae), increased in a majority of the study subjects.

    Clearly, there are risks associated with international travel and these risks include outside factors as well as the personal behaviour of travellers. We believe our results can be used to develop better pre-travel advice for tourists as well as university students studying abroad resulting in safer travel.

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  • 34.
    Angelin, Martin
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Evengård, Birgitta
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Palmgren, Helena
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Travel and vaccination patterns: a report from a travel medicine clinic in northern Sweden2011In: Scandinavian Journal of Infectious Diseases, ISSN 0036-5548, E-ISSN 1651-1980, Vol. 43, no 9, p. 714-720Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The Travel Medicine Clinic in Umeå is one of Sweden's largest public providers of vaccination and counselling prior to international travel. During the study period it was the only travel medicine clinic in Umeå. This study describes the demography of the visitors to the clinic and travel destinations and durations, as well as vaccinations administered. METHODS: This was a retrospective study for the period January 2005 to April 2008 based on pre-travel consultation questionnaires and on vaccine expenditure data. A 10% sample of 16,735 first visits prior to international travel was consecutively selected according to the chronology of the visits. RESULTS: Data on 1698 travellers were included in the study. Thailand was the most common destination among visitors, accounting for one third of all destinations. Medical problems affecting pre-travel health planning were rare. Four out of 5 visitors (79%) received only 1 vaccination, mainly for hepatitis A. Travellers to Thailand more often sought travel health advice compared to travellers to Turkey, despite the fact that the 2 destinations were almost equally distributed among travellers from Umeå. We found differences between men and women in money spent on vaccines and in particular in vaccination against Japanese encephalitis. CONCLUSIONS: To assess the optimal vaccination level at a travel medicine clinic is difficult. Decisions are affected by general recommendations and the risk perception of the travel medicine practitioner, as well as the risk perception of the traveller. The sex difference found in this study might be due to gender differences in risk perception and should be further investigated.

  • 35.
    Angelin, Martin
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Evengård, Birgitta
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Palmgren, Helena
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Travel health advice: Benefits, compliance, and outcome2014In: Scandinavian Journal of Infectious Diseases, ISSN 0036-5548, E-ISSN 1651-1980, Vol. 46, no 6, p. 447-453Article in journal (Refereed)
    Abstract [en]

    Background: Travel health advice is an important and difficult part of a pre-travel consultation. The aim of this study was to determine whether the travel health advice given is followed by the traveller and whether it affects disease and injury experienced during travel. Methods: A prospective survey study was carried out from October 2009 to April 2012 at the Travel Medicine Clinic of the Department of Infectious Diseases, Umea University Hospital, Umea, Sweden. The Travel Medicine Clinic in Umea is the largest travel clinic in northern Sweden. Results: We included 1277 individuals in the study; 1059 (83%) responded to the post-travel questionnaire. Most visitors (88%) remembered having received travel health advice; among these, 95% found some of the health advice useful. Two-thirds (67%) claimed to have followed the advice, but fell ill during travel to the same extent as those who did not. Younger travellers (< 31 y) found our travel health advice less beneficial, were less compliant with the advice, took more risks during travel, and fell ill during travel to a greater extent than older travellers. Conclusions: Helping travellers stay healthy during travel is the main goal of travel medicine. Younger travellers are a risk group for illness during travel and there is a need to find new methods to help them avoid illness. Travellers find travel health advice useful, but it does not protect them from travel-related illness. Factors not easily influenced by the traveller play a role, but a comprehensive analysis of the benefits of travel health advice is needed.

  • 36.
    Angelin, Martin
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Forsell, Joakim
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Bacteriology.
    Granlund, Margareta
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Bacteriology.
    Evengård, Birgitta
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Palmgren, Helena
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Johansson, Anders
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Bacteriology. Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS).
    Risk factors for colonization with extended-spectrum beta-lactamase producing Enterobacteriaceae in healthcare students on clinical assignment abroad: A prospective study2015In: Travel Medicine and Infectious Disease, ISSN 1477-8939, E-ISSN 1873-0442, Vol. 13, no 3, p. 223-229Article in journal (Refereed)
    Abstract [en]

    Background: The increase of antibiotic resistance in clinically important bacteria is a worldwide threat, especially in healthcare environments. International travel is a risk factor for gut colonization with extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-PE). The risk for healthcare students of being colonized with ESBL-PE when participating in patient-related work abroad has not been previously investigated. Methods: Swedish healthcare students travelling for pre-clinical and clinical courses outside Scandinavia submitted faecal samples and survey data before and after travel. The faecal samples were screened for ESBL-PE and carbapenemase-producing Enterobacteriaceae (CPE). Screening results and survey data were analysed to identify risk factors for colonization. Results: In the 99 subjects who submitted a full set of samples, 35% were colonized with a new ESBL-PE strain during travel. No CPE was found. The most important risk factor for ESBL-PE colonization was travel destination, and the highest colonization rate was found in the South East Asia region. Antibiotic treatment during travel was an independent risk factor for ESBL-PE colonization but patient-related work was not significantly associated with an increased risk. Conclusions: Patient-related work abroad was not a risk factor for ESBL-PE suggesting that transmission from patients is uncommon. Pre-travel advice on avoiding unnecessary antibiotic treatment during travel is recommended.

  • 37.
    Angelin, Martin
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Sjölin, Jan
    Department of Medical Sciences, Section of Infectious Diseases, Uppsala University, Sweden.
    Kahn, Fredrik
    Department of Clinical Sciences, Division of Infection Medicine, Lund University, Sweden.
    Ljunghill Hedberg, Anna
    Department of Medical Sciences, Section of Infectious Diseases, Uppsala University, Sweden.
    Rosdahl, Anja
    School of Medical Sciences, Örebro University, Örebro, Sweden; Department of Infectious Diseases, Örebro University Hospital, Örebro, Sweden.
    Skorup, Paul
    Department of Medical Sciences, Section of Infectious Diseases, Uppsala University, Sweden.
    Werner, Simon
    Department of Infectious Diseases, Skåne University Hospital, Region Skåne, Malmö, Sweden.
    Woxenius, Susanne
    Department of Infectious Diseases, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Askling, Helena H.
    Department of Medicine, Division of Infectious Diseases, Karolinska Institutet, Solna, Sweden; Academic Specialist Centre, Stockholm County Health Care Services, Region Stockholm, Sweden.
    Qdenga® - A promising dengue fever vaccine; can it be recommended to non-immune travelers?2023In: Travel Medicine and Infectious Disease, ISSN 1477-8939, E-ISSN 1873-0442, Vol. 54, article id 102598Article in journal (Refereed)
    Abstract [en]

    Qdenga® has been approved by the European Medicines Agency (EMA) for individuals > 4 years of age and for use according to national recommendations. The vaccine shows high efficacy against virologically confirmed dengue and severe dengue in clinical studies on 4–16-year old's living in endemic areas. For individuals 16–60 years old only serological data exists and there is no data for individuals > 60 years. Its use as a travel vaccine is still unclear. We present the studies behind the approval and the recommendations for travelers as issued by the Swedish Society for Infectious Diseases Physicians.

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  • 38. Angelo, Kristina M.
    et al.
    Stoney, Rhett J.
    Brun-Cottan, Gaelle
    Leder, Karin
    Grobusch, Martin P.
    Hochberg, Natasha
    Kuhn, Susan
    Bottieau, Emmanuel
    Schlagenhauf, Patricia
    Chen, Lin
    Hynes, Noreen A.
    Perez, Cecilia Perret
    Mockenhaupt, Frank P.
    Molina, Israel
    Crespillo-Andujar, Clara
    Malvy, Denis
    Caumes, Eric
    Plourde, Pierre
    Shaw, Marc
    McCarthy, Anne E.
    Piper-Jenks, Nancy
    Connor, Bradley A.
    Hamer, Davidson H.
    Wilder-Smith, Annelies
    Umeå University, Faculty of Medicine, Department of Epidemiology and Global Health.
    Zika among international travellers presenting to GeoSentinel sites, 2012-2019: implications for clinical practice2020In: Journal of Travel Medicine, ISSN 1195-1982, E-ISSN 1708-8305, Vol. 27, no 4, article id taaa061Article in journal (Refereed)
    Abstract [en]

    Introduction: International travellers contribute to the rapid spread of Zika virus (ZIKV) and its sentinel identification globally. We describe ZIKV infections among international travellers seen at GeoSentinel sites with a focus on ZIKV acquired in the Americas and the Caribbean, describe countries of exposure and traveller characteristics, and assess ZIKV diagnostic testing by site. Methods: Records with an international travel-related diagnosis of confirmed or probable ZIKV from January 2012 through December 2019 reported to GeoSentinel with a recorded illness onset date were included to show reported cases over time. Records from March 2016 through December 2019 with an exposure region of the Americas or the Caribbean were included in the descriptive analysis. A survey was conducted to assess the availability, accessibility and utilization of ZIKV diagnostic tests at GeoSentinel sites. Results: GeoSentinel sites reported 525 ZIKV cases from 2012 through 2019. Between 2012 and 2014, eight cases were reported, and all were acquired in Asia or Oceania. After 2014, most cases were acquired in the Americas or the Caribbean, a large decline in ZIKV cases occurred in 2018-19. Between March 2016 and December 2019, 423 patients acquired ZIKV in the Americas or the Caribbean, peak reporting to these regions occurred in 2016 [330 cases (78%)]. The median age was 36 years (range: 3-92); 63% were female. The most frequent region of exposure was the Caribbean (60%). Thirteen travellers were pregnant during or after travel; one had a sexually acquired ZIKV infection. There was one case of fetal anomaly and two travellers with Guillain-Barre syndrome. GeoSentinel sites reported various challenges to diagnose ZIKV effectively. Conclusion: ZIKV should remain a consideration for travellers returning from areas with risk of ZIKV transmission. Travellers should discuss their travel plans with their healthcare providers to ensure ZIKV prevention measures are taken.

  • 39.
    Antti, Henrik
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    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).
    Näsström, Elin
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Kouremenos, Konstantinos
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS). Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR).
    Sundén-Cullberg, Jonas
    Guo, Yongzhi
    Moritz, Thomas
    Wolf-Watz, Hans
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS). Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR).
    Johansson, Anders
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Fällman, Maria
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS). Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR).
    Metabolic profiling for detection of staphylococcus aureus infection and antibiotic resistance2013In: PLOS ONE, E-ISSN 1932-6203, Vol. 8, no 2, article id e56971Article in journal (Refereed)
    Abstract [en]

    Due to slow diagnostics, physicians must optimize antibiotic therapies based on clinical evaluation of patients without specific information on causative bacteria. We have investigated metabolomic analysis of blood for the detection of acute bacterial infection and early differentiation between ineffective and effective antibiotic treatment. A vital and timely therapeutic difficulty was thereby addressed: the ability to rapidly detect treatment failures because of antibiotic-resistant bacteria. Methicillin-resistant (MRSA) and methicillin-sensitive (MSSA) were used and for infecting mice, while natural MSSA infection was studied in humans. Samples of bacterial growth media, the blood of infected mice and of humans were analyzed with combined Gas Chromatography/Mass Spectrometry. Multivariate data analysis was used to reveal the metabolic profiles of infection and the responses to different antibiotic treatments. experiments resulted in the detection of 256 putative metabolites and mice infection experiments resulted in the detection of 474 putative metabolites. Importantly, ineffective and effective antibiotic treatments were differentiated already two hours after treatment start in both experimental systems. That is, the ineffective treatment of MRSA using cloxacillin and untreated controls produced one metabolic profile while all effective treatment combinations using cloxacillin or vancomycin for MSSA or MRSA produced another profile. For further evaluation of the concept, blood samples of humans admitted to intensive care with severe sepsis were analyzed. One hundred thirty-three putative metabolites differentiated severe MSSA sepsis (n = 6) from severe sepsis (n = 10) and identified treatment responses over time. Combined analysis of human, , and mice samples identified 25 metabolites indicative of effective treatment of sepsis. Taken together, this study provides a proof of concept of the utility of analyzing metabolite patterns in blood for early differentiation between ineffective and effective antibiotic treatment in acute infections.

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  • 40. Aoki, Koki
    et al.
    Benkö, Mária
    Davison, Andrew J
    De Jong, Jan C
    Echavarria, Marcela
    Erdman, Dean D
    Harrach, Balázs
    Kajon, Adriana E
    Schnurr, David
    Wadell, Göran
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Towards an integrated human adenovirus designation system that utilizes molecular and serological data and serves both clinical and fundamental virology2011In: Journal of Virology, ISSN 0022-538X, E-ISSN 1098-5514, Vol. 85, no 11, p. 5703-5704Article in journal (Refereed)
  • 41. Arbeitman, Claudia R.
    et al.
    Rojas, Pablo
    Ojeda-May, Pedro
    Umeå University, Faculty of Science and Technology, High Performance Computing Center North (HPC2N). Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Garcia, Martin E.
    The SARS-CoV-2 spike protein is vulnerable to moderate electric fields2021In: Nature Communications, E-ISSN 2041-1723, Vol. 12, no 1, article id 5407Article in journal (Refereed)
    Abstract [en]

    Most of the ongoing projects aimed at the development of specific therapies and vaccines against COVID-19 use the SARS-CoV-2 spike (S) protein as the main target. The binding of the spike protein with the ACE2 receptor (ACE2) of the host cell constitutes the first and key step for virus entry. During this process, the receptor binding domain (RBD) of the S protein plays an essential role, since it contains the receptor binding motif (RBM), responsible for the docking to the receptor. So far, mostly biochemical methods are being tested in order to prevent binding of the virus to ACE2. Here we show, with the help of atomistic simulations, that external electric fields of easily achievable and moderate strengths can dramatically destabilise the S protein, inducing long-lasting structural damage. One striking field-induced conformational change occurs at the level of the recognition loop L3 of the RBD where two parallel beta sheets, believed to be responsible for a high affinity to ACE2, undergo a change into an unstructured coil, which exhibits almost no binding possibilities to the ACE2 receptor. We also show that these severe structural changes upon electric-field application also occur in the mutant RBDs corresponding to the variants of concern (VOC) B.1.1.7 (UK), B.1.351 (South Africa) and P.1 (Brazil). Remarkably, while the structural flexibility of S allows the virus to improve its probability of entering the cell, it is also the origin of the surprising vulnerability of S upon application of electric fields of strengths at least two orders of magnitude smaller than those required for damaging most proteins. Our findings suggest the existence of a clean physical method to weaken the SARS-CoV-2 virus without further biochemical processing. Moreover, the effect could be used for infection prevention purposes and also to develop technologies for in-vitro structural manipulation of S. Since the method is largely unspecific, it can be suitable for application to other mutations in S, to other proteins of SARS-CoV-2 and in general to membrane proteins of other virus types.

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  • 42.
    Arvidsson, Malin
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Five-year follow-up after the outbreak of Cryptosporidium hominis in Östersund2018Independent thesis Basic level (professional degree), 20 credits / 30 HE creditsStudent thesis
  • 43. Asghar, Naveed
    et al.
    Lee, Yi-Ping
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology. Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS).
    Nilsson, Emma
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology. Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS).
    Lindqvist, Richard
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology. Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS).
    Melik, Wessam
    Kröger, Andrea
    Överby, Anna K.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology. Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS).
    Johansson, Magnus
    The role of the poly(A) tract in the replication and virulence of tick-borne encephalitis virus2016In: Scientific Reports, E-ISSN 2045-2322, Vol. 6, article id 39265Article in journal (Refereed)
    Abstract [en]

    The tick-borne encephalitis virus (TBEV) is a flavivirus transmitted to humans, usually via tick bites. The virus causes tick-borne encephalitis (TBE) in humans, and symptoms range from mild flu-like symptoms to severe and long-lasting sequelae, including permanent brain damage. It has been suggested that within the population of viruses transmitted to the mammalian host, quasispecies with neurotropic properties might become dominant in the host resulting in neurological symptoms. We previously demonstrated the existence of TBEV variants with variable poly(A) tracts within a single blood-fed tick. To characterize the role of the poly(A) tract in TBEV replication and virulence, we generated infectious clones of Toro-2003 with the wild-type (A)(3)C(A)(6) sequence (Toro-6A) or with a modified (A)(3)C(A)(38) sequence (Toro-38A). Toro-38A replicated poorly compared to Toro-6A in cell culture, but Toro-38A was more virulent than Toro-6A in a mouse model of TBE. Next-generation sequencing of TBEV genomes after passaging in cell culture and/or mouse brain revealed mutations in specific genomic regions and the presence of quasispecies that might contribute to the observed differences in virulence. These data suggest a role for quasispecies development within the poly(A) tract as a virulence determinant for TBEV in mice.

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  • 44. Asghar, Naveed
    et al.
    Lindblom, Pontus
    Melik, Wessam
    Lindqvist, Richard
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Haglund, Mats
    Forsberg, Pia
    Överby, Anna K.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Andreassen, Åshild
    Lindgren, Per-Eric
    Johansson, Magnus
    Tick-borne encephalitis virus sequenced directly from questing and blood-feeding ticks reveals quasispecies variance2014In: PLOS ONE, E-ISSN 1932-6203, Vol. 9, no 7, p. e103264-Article in journal (Refereed)
    Abstract [en]

    The increased distribution of the tick-borne encephalitis virus (TBEV) in Scandinavia highlights the importance of characterizing novel sequences within the natural foci. In this study, two TBEV strains: the Norwegian Mandal 2009 (questing nymphs pool) and the Swedish Saringe 2009 (blood-fed nymph) were sequenced and phylogenetically characterized. Interestingly, the sequence of Mandal 2009 revealed the shorter form of the TBEV genome, similar to the highly virulent Hypr strain, within the 3' non-coding region (3'NCR). A different genomic structure was found in the 3'NCR of Saringe 2009, as in-depth analysis demonstrated TBEV variants with different lengths within the poly(A) tract. This shows that TBEV quasispecies exists in nature and indicates a putative shift in the quasispecies pool when the virus switches between invertebrate and vertebrate environments. This prompted us to further sequence and analyze the 3'NCRs of additional Scandinavian TBEV strains and control strains, Hypr and Neudoerfl. Toro 2003 and Habo 2011 contained mainly a short (A) 3C(A)6 poly(A) tract. A similar pattern was observed for the human TBEV isolates 1993/783 and 1991/4944; however, one clone of 1991/4944 contained an (A) 3C(A)11 poly(A) sequence, demonstrating that quasispecies with longer poly(A) could be present in human isolates. Neudoerfl has previously been reported to contain a poly(A) region, but to our surprise the resequenced genome contained two major quasispecies variants, both lacking the poly(A) tract. We speculate that the observed differences are important factors for the understanding of virulence, spread, and control of the TBEV.

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  • 45.
    Ayeni, Oluwatosin A.
    et al.
    Faculty of Health Sciences, Division of Epidemiology and biostatistics, School of Public Health, University of the Witwatersrand, Johannesburg, South Africa.
    Walaza, Sibongile
    Faculty of Health Sciences, Division of Epidemiology and biostatistics, School of Public Health, University of the Witwatersrand, Johannesburg, South Africa; National Institute for Communicable Diseases of the National Health Laboratory Service, Centre for Respiratory Diseases and Meningitis, Johannesburg, South Africa.
    Tempia, Stefano
    Faculty of Health Sciences, Division of Epidemiology and biostatistics, School of Public Health, University of the Witwatersrand, Johannesburg, South Africa; Influenza Division, Centers for Disease Control and Prevention, GA, Atlanta, United States; Influenza Programme, Centers for Disease Control and Prevention-South Africa, Pretoria, South Africa; Mass Genics, GA, Duluth, United States.
    Groome, Michelle
    Faculty of Health Sciences, Medical Research Council, Respiratory and Meningeal Pathogens Research Unit, University of the Witwatersrand, Johannesburg, South Africa; Department of Science and Technology, National Research Foundation: Vaccine Preventable Diseases, University of the Witwatersrand, Johannesburg, South Africa.
    Kahn, Kathleen
    Umeå University, Faculty of Medicine, Department of Epidemiology and Global Health. Faculty of Health Sciences, MRC/Wits Rural Public Health and Health Transitions Research Unit (Agincourt), School of Public Health, University of the Witwatersrand, Johannesburg, South Africa; INDEPTH Network, Accra, Ghana.
    Madhi, Shabir A.
    National Institute for Communicable Diseases of the National Health Laboratory Service, Centre for Respiratory Diseases and Meningitis, Johannesburg, South Africa; Faculty of Health Sciences, Medical Research Council, Respiratory and Meningeal Pathogens Research Unit, University of the Witwatersrand, Johannesburg, South Africa; Department of Science and Technology, National Research Foundation: Vaccine Preventable Diseases, University of the Witwatersrand, Johannesburg, South Africa.
    Cohen, Adam L.
    Influenza Division, Centers for Disease Control and Prevention, GA, Atlanta, United States; Influenza Programme, Centers for Disease Control and Prevention-South Africa, Pretoria, South Africa.
    Moyes, Jocelyn
    National Institute for Communicable Diseases of the National Health Laboratory Service, Centre for Respiratory Diseases and Meningitis, Johannesburg, South Africa.
    Venter, Marietjie
    Department of Medical Virology, University of Pretoria, Pretoria, South Africa.
    Pretorius, Marthi
    National Institute for Communicable Diseases of the National Health Laboratory Service, Centre for Respiratory Diseases and Meningitis, Johannesburg, South Africa; Department of Medical Virology, University of Pretoria, Pretoria, South Africa.
    Treurnicht, Florette
    National Institute for Communicable Diseases of the National Health Laboratory Service, Centre for Respiratory Diseases and Meningitis, Johannesburg, South Africa.
    Hellferscee, Orienka
    Faculty of Health Sciences, Division of Epidemiology and biostatistics, School of Public Health, University of the Witwatersrand, Johannesburg, South Africa; School of Pathology, University of the Witwatersrand, Johannesburg, South Africa.
    Von Gottberg, Anne
    National Institute for Communicable Diseases of the National Health Laboratory Service, Centre for Respiratory Diseases and Meningitis, Johannesburg, South Africa; School of Pathology, University of the Witwatersrand, Johannesburg, South Africa; Division of Infectious Diseases, Hubert Department of Global Health, Rollins School of Public Health, School of Medicine, Emory University, GA, Atlanta, United States.
    Wolter, Nicole
    National Institute for Communicable Diseases of the National Health Laboratory Service, Centre for Respiratory Diseases and Meningitis, Johannesburg, South Africa; School of Pathology, University of the Witwatersrand, Johannesburg, South Africa.
    Cohen, Cheryl
    Faculty of Health Sciences, Division of Epidemiology and biostatistics, School of Public Health, University of the Witwatersrand, Johannesburg, South Africa; National Institute for Communicable Diseases of the National Health Laboratory Service, Centre for Respiratory Diseases and Meningitis, Johannesburg, South Africa.
    Mortality in children aged <5 years with severe acute respiratory illness in a high HIV-prevalence urban and rural areas of South Africa, 2009–20132021In: PLOS ONE, E-ISSN 1932-6203, Vol. 16, no 8, article id e0255941Article in journal (Refereed)
    Abstract [en]

    Background: Severe acute respiratory illness (SARI) is an important cause of mortality in young children, especially in children living with HIV infection. Disparities in SARI death in children aged <5 years exist in urban and rural areas.

    Objective: To compare the factors associated with in-hospital death among children aged <5 years hospitalized with SARI in an urban vs. a rural setting in South Africa from 2009–2013.

    Methods: Data were collected from hospitalized children with SARI in one urban and two rural sentinel surveillance hospitals. Nasopharyngeal aspirates were tested for ten respiratory viruses and blood for pneumococcal DNA using polymerase chain reaction. We used multivariable logistic regression to identify patient and clinical characteristics associated with in-hospital death.

    Results: From 2009 through 2013, 5,297 children aged <5 years with SARI-associated hospital admission were enrolled; 3,811 (72%) in the urban and 1,486 (28%) in the rural hospitals. In-hospital case-fatality proportion (CFP) was higher in the rural hospitals (6.9%) than the urban hospital (1.3%, p<0.001), and among HIV-infected than the HIV-uninfected children (9.6% vs. 1.6%, p<0.001). In the urban hospital, HIV infection (odds ratio (OR):11.4, 95% confidence interval (CI):5.4–24.1) and presence of any other underlying illness (OR: 3.0, 95% CI: 1.0–9.2) were the only factors independently associated with death. In the rural hospitals, HIV infection (OR: 4.1, 95% CI: 2.3–7.1) and age <1 year (OR: 3.7, 95% CI: 1.9–7.2) were independently associated with death, whereas duration of hospitalization ≥5 days (OR: 0.5, 95% CI: 0.3–0.8) and any respiratory virus detection (OR: 0.4, 95% CI: 0.3–0.8) were negatively associated with death.

    Conclusion: We found that the case-fatality proportion was substantially higher among children admitted to rural hospitals and HIV infected children with SARI in South Africa. While efforts to prevent and treat HIV infections in children may reduce SARI deaths, further efforts to address health care inequality in rural populations are needed.

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  • 46. Baharom, Faezzah
    et al.
    Rankin, Gregory
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Scholz, Saskia
    Pourazar, Jamshid
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Ahlm, Clas
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Blomberg, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Smed-Sörensen, Anna
    Human lung dendritic cells: spatial distribution and phenotypic identification in endobronchial biopsies using immunohistochemistry and flow cytometry2017In: Journal of Visualized Experiments, E-ISSN 1940-087X, no 119, article id e55222Article in journal (Refereed)
    Abstract [en]

    The lungs are constantly exposed to the external environment, which in addition to harmless particles, also contains pathogens, allergens, and toxins. In order to maintain tolerance or to induce an immune response, the immune system must appropriately handle inhaled antigens. Lung dendritic cells (DCs) are essential in maintaining a delicate balance to initiate immunity when required without causing collateral damage to the lungs due to an exaggerated inflammatory response. While there is a detailed understanding of the phenotype and function of immune cells such as DCs in human blood, the knowledge of these cells in less accessible tissues, such as the lungs, is much more limited, since studies of human lung tissue samples, especially from healthy individuals, are scarce. This work presents a strategy to generate detailed spatial and phenotypic characterization of lung tissue resident DCs in healthy humans that undergo a bronchoscopy for the sampling of endobronchial biopsies. Several small biopsies can be collected from each individual and can be subsequently embedded for ultrafine sectioning or enzymatically digested for advanced flow cytometric analysis. The outlined protocols have been optimized to yield maximum information from small tissue samples that, under steady-state conditions, contain only a low frequency of DCs. While the present work focuses on DCs, the methods described can directly be expanded to include other (immune) cells of interest found in mucosal lung tissue. Furthermore, the protocols are also directly applicable to samples obtained from patients suffering from pulmonary diseases where bronchoscopy is part of establishing the diagnosis, such as chronic obstructive pulmonary disease (COPD), sarcoidosis, or lung cancer.

  • 47.
    Bailey, Leslie
    et al.
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Engström, Patrik
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    Nordström, Anna
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Rehabilitation Medicine. Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Bergström, Sven
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Waldenström, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Nordström, Peter
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
    Chlamydia pneumoniae infection results in generalized bone loss in mice2008In: Microbes and infection, ISSN 1286-4579, E-ISSN 1769-714X, Vol. 10, no 10-11, p. 1175-1181Article in journal (Refereed)
  • 48.
    Bala, Anju
    et al.
    Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR). Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Uhlin, Bernt Eric
    Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR). Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Karah, Nabil
    Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR). Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Insights into the genetic contexts of sulfonamide resistance among early clinical isolates of Acinetobacter baumannii2023In: Infection, Genetics and Evolution, ISSN 1567-1348, E-ISSN 1567-7257, Vol. 112, article id 105444Article in journal (Refereed)
    Abstract [en]

    Since the late 1930s, resistance to sulfonamides has been accumulating across bacterial species including Acinetobacter baumannii, an opportunistic pathogen increasingly implicated the spread of antimicrobial resistance worldwide. Our study aimed to explore events involved in the acquisition of sulfonamide resistance genes, particularly sul2, among the earliest available isolates of A. baumannii. The study utilized the genomic data of 19 strains of A. baumannii isolated before 1985. The whole genomes of 5 clinical isolates obtained from the Culture Collection University of Göteborg (CCUG), Sweden, were sequenced using the Illumina MiSeq system. Acquired resistance genes, insertion sequence elements and plasmids were detected using ResFinder, ISfinder and Plasmidseeker, respectively, while sequence types (STs) were assigned using the PubMLST Pasteur scheme. BLASTn was used to verify the occurrence of sul genes and to map their genetic surroundings. The sul1 and sul2 genes were detected in 4 and 9 isolates, respectively. Interestingly, sul2 appeared thirty years earlier than sul1. The sul2 gene was first located in the genomic island GIsul2 located on a plasmid, hereafter called NCTC7364p. With the emergence of international clone 1, the genetic context of sul2 evolved toward transposon Tn6172, which was also plasmid-mediated. Sulfonamide resistance in A. baumannii was efficiently acquired and transferred vertically, e.g., among the ST52 and ST1 isolates, as well as horizontally among non-related strains by means of a few efficient transposons and plasmids. Timely acquisition of the sul genes has probably contributed to the survival skill of A. baumannii under the high antimicrobial stress of hospital settings.

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  • 49. Balasingam, Shobana
    et al.
    Wilder-Smith, Annelies
    Lee Kong Chian School of Medicine, Nanyang Technology University, Singapore 308232, Singapore.
    Randomized controlled trials for influenza drugs and vaccines: a review of controlled human infection studies2016In: International Journal of Infectious Diseases, ISSN 1201-9712, E-ISSN 1878-3511, Vol. 49, p. 18-29Article, review/survey (Refereed)
    Abstract [en]

    OBJECTIVES: Controlled human infection, the intentional infection of healthy volunteers, allows disease pathogenesis to be studied and vaccines and therapeutic interventions to be evaluated in a controlled setting. A systematic review of randomized controlled trials of countermeasures for influenza that used the experimental human infection platform was performed. The primary objective was to document the scope of trials performed to date and the main efficacy outcome in the trials. The secondary objective was to assess safety and identify serious adverse events.

    METHODS: The PubMed database was searched for randomized controlled influenza human challenge studies with predetermined search terms. Review papers, papers without outcomes, community-acquired infections, duplicated data, pathogenesis studies, and observational studies were excluded.

    RESULTS: Twenty-six randomized controlled trials published between 1947 and 2014 fit the study inclusion criteria. Two-thirds of these trials investigated antivirals and one-third investigated influenza vaccines. Among 2462 subjects inoculated with influenza virus, the incidence of serious adverse events was low (0.04%). These challenge studies helped to down-select three antivirals and one vaccine that were subsequently approved by the US Food and Drug Administration (FDA).

    CONCLUSIONS: Controlled human infection studies are an important research tool in assessing promising influenza vaccines and antivirals. These studies are performed quickly and are cost-effective and safe, with a low incidence of serious adverse events.

  • 50.
    Bancroft, Dani
    et al.
    Department of Public Health, Environments and Society, London School of Hygiene and Tropical Medicine, London, United Kingdom.
    Power, Grace M.
    Department of Disease Control, London School of Hygiene & Tropical Medicine, London, United Kingdom.
    Jones, Robert T.
    Department of Disease Control, London School of Hygiene & Tropical Medicine, London, United Kingdom.
    Massad, Eduardo
    School of Medicine, University of São Paulo, São Paulo, Brazil; School of Applied Mathematics, Fundação Getulio Vargas, RJ, Rio de Janeiro, Brazil.
    Iriat, Jorge Bernstein
    Institute of Collective Health, Federal University of Bahia, Salvador, BA, Brazil.
    Preet, Raman
    Umeå University, Faculty of Medicine, Department of Epidemiology and Global Health.
    Kinsman, John
    Umeå University, Faculty of Medicine, Department of Epidemiology and Global Health.
    Logan, James G.
    Department of Disease Control, London School of Hygiene & Tropical Medicine, London, United Kingdom.
    Vector control strategies in Brazil: a qualitative investigation into community knowledge, attitudes and perceptions following the 2015-2016 Zika virus epidemic2022In: BMJ Open, E-ISSN 2044-6055, Vol. 12, no 1, article id e050991Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: The World Health Organization declared a Public Health Emergency of International Concern following the rapid emergence of neonatal microcephaly in Brazil during the 2015-2016 Zika virus (ZIKV) epidemic. In response, a national campaign sought to control Aedes mosquito populations and reduce ZIKV transmission. Achieving adherence to vector control or mosquito-bite reduction behaviours, including the use of topical mosquito repellents, is challenging. Coproduction of research at the community level is needed to understand and mitigate social determinants of lower engagement with Aedes preventive measures, particularly within disempowered groups.

    DESIGN: In 2017, the Zika Preparedness Latin America Network (ZikaPLAN) conducted a qualitative study to understand individual and community level experiences of ZIKV and other mosquito-borne disease outbreaks. Presented here is a thematic analysis of 33 transcripts from community focus groups and semistructured interviews, applying the Health Belief Model (HBM) to elaborate knowledge, attitudes and perceptions of ZIKV and vector control strategies.

    PARTICIPANTS: 120 purposively sampled adults of approximate reproductive age (18-45); 103 women participated in focus groups and 17 men in semistructured interviews.

    SETTING: Two sociopolitically and epidemiologically distinct cities in Brazil: Jundiaí (57 km north of São Paolo) and Salvador (Bahia state capital).

    RESULTS: Four key and 12 major themes emerged from the analysis: (1) knowledge and cues to action; (2) attitudes and normative beliefs (perceived threat, barriers, benefits and self-efficacy); (3) behaviour change (household prevention and community participation); and (4) community preferences for novel repellent tools, vector control strategies and ZIKV messaging.

    CONCLUSIONS: Common barriers to repellent adherence were accessibility, appearance and effectiveness. A strong case is made for the transferability of the HBM to inform epidemic preparedness for mosquito-borne disease outbreaks at the community level. Nationally, a health campaign targeting men is recommended, in addition to local mobilisation of funding to strengthen surveillance, risk communication and community engagement.

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