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NEWSLETTER Special Edition | 12.2015 Grensoverschrijdende activiteiten A lg e m e n e in fo r m atie O n d e r w ij s e n o p le id in g O n d e r z o e k / R e s e a r c h P a t i ë n t e n z o rg e n d ia g n ostie k Medische Microbiologie A lg e m e n e in fo r m atie O n d e r w ij s e n o p le id in g O n d e r z o e k / R e s e a r c h P a t i ë n t e n z o rg e n d ia g n ostie k Medische Microbiologie Medical Microbiology & Infection Prevention For the website, click on the circle. Microbes in Health & Disease Science Day 2015

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Page 1: Medical Microbiology & Infection Prevention NEWSLETTER ... › SiteCollectionDocuments › UMCG › Afdelingen … · NEWSLETTER Special Edition | 12.2015 G r e n s o v e r s c h

NEWSLETTER Special Edition | 12.2015

Grensoverschrijd

ende acti

viteit

en

Algemene informatie

Onderw

ijs en opleiding

Onderzoek / Research

Patië

nten

zorg en diagnostiek

MedischeMicrobiologie

Algemene informatie

Onderw

ijs en opleiding

Onderzoek / Research

Patië

nten

zorg en diagnostiek

MedischeMicrobiologie

Medical Microbiology & Infection Prevention

For the website, click on the circle.

Microbes in Health & Disease Science Day 2015

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© MMB Newsletter Special Edition 12.2015 • Medical Microbiology and Infection Prevention © MMB Newsletter Special Edition 12.2015 • Medical Microbiology and Infection Prevention

Infections and infectious diseases are back and an increasing burden to health worldwide. Especially, drug resistance is a major challenge in the years to come. The main research questions here are related to the prevention, adequate and early detection as well as optimal and personalized therapy of infections.

As infections and infectious diseases are communicable, all three pillars are necessary to form the preventive cluster. Prevention measures, such as the development of vaccines and reduction of transmission are well-known. But, also the understanding of risk behaviour, tracing sources of infections, OneHealth epidemiology, specific and imaging-related diagnostics as well as the understanding of the composition and influence of the human micro-biome help to implement primary prevention measures.

As not all infections can be prevented, analysis of pathogens (including detection and subtyping) , but also of possible health-related microorganisms ('hygienogens') can be used for

optimalization of the therapy, but are basically secondary prevention as more precise preventive measures can be implemented. This way,

further spread can be fostered or in the case of pathogens reduced. Finally, all research related to novel and new forms of therapy of infections (including targeted drug delivery, possible use of radiotherapy and immunotherapeutics) helps to restore health and is concomitantly tertiary prevention, as transmission of pathogens to other individuals becomes less probable. All in all, research in MHD is research on how to prevent communicable diseases and in consequence how to maintain health. An excellent example of healthy ageing research.

During the MHD Science Day 2015 mainly young investigators from the different MHD research groups presented their work, which is presented in this newsletter. Enjoy reading it!

Alex Friedrich, Chair and Head of the Department Medical Microbiology and Infection Prevention

The second Science Day of Microbes in Health and Disease (MHD) was held on November 10th, 2015. During this day, thirteen PhD students from the different departments united in MHD presented the results of their research projects. The topics ranged from basic to translational to clinical studies thereby nicely reflecting the diversity of MHD. Furthermore, clinical microbiologist of LabMicta, Felix Geeraedts, told an impressive story about his work as a team captain in a mobile Ebola lab in Liberia. The team struggled to convince local health care workers to test for Ebola. His perseverance and creativity were nicely illustrated by his method to prepare Dutch coffee.

The Organizing Committee rated the presentations from the PhD students and compared the mean scores. No scores were given by committee members supervising the presenting PhD student. Tabitha Hoornweg was the speaker of the day. Her videos on the chikungunya virus were very impressive and nicely illustrated her

scientific activities for the broad public that attended the Science Day.

Andrea García Perez and Tim Stobernack shared the second position on our ranking list. We found that both speakers did an excellent job in translating their research for a broad academic public and they discussed their results with

fervor. Importantly, we were very impressed by all speakers.

The scientific content of all presentations was good and this enabled lively discussions with the audience. Also we would like to thank the session chairs but luckily their task was not very demanding as all speakers presented their research within the time frame available.We would like to welcome Annelies Riezebos-Brilman to the Organizing Committee for next year. She will take over from Jolanda Smit after three years. We are extremely grateful for the outstanding organization by Jolanda Oldengarm -Leidelmeijer. Our Science Day perfectly shows the diversity and the opportunities within MHD and we are looking forward to the next Science Day on Tuesday November 8th, 2016!

Jan-Willem Alffenaar, Jolanda Smit and Ymkje StienstraOrganizing Committee of the Microbes in Health & Disease Science Day UMCG

Figure: Welcome by Alex Friedrich

Figure: Members of the organizing committee Ymkje Stienstra and Jan Willem Alffenaar with Jolanda Oldengarm -Leidelmeijer

Figure: Best speaker Tabitha Hoornweg and chair Izabela Rodenhuis-Zybert

Figure: Second best speaker Tim Stobernack and chair Izabela Rodenhuis-Zybert

Figure: Second best speaker Andrea García Perez and chair John Rossen

Microbes in Health & Disease Science Day UMCG

Research in Microbes in Health & Disease (MHD) is Research in Healthy Ageing

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© MMB Newsletter Special Edition 12.2015 • Medical Microbiology and Infection Prevention © MMB Newsletter Special Edition 12.2015 • Medical Microbiology and Infection Prevention

Session 1 Fulvio M. Reggiori, chair of session 1

Session 2 Izabela A. Rodenhuis-Zybert, chair of session 2

Session 3 John W.A. Rossen, chair of session 3

Session 4 Annelies Riezebos-Brilman, chair of session 4

Fulvio M. Reggiori, PhDAssociate Professor at the Department of Cell Biology

The research group of Fulvio Reggiori is working on the dissection of the mechanism and regulation of the catabolic pathway of autophagy. One of the research lines in his laboratory aims to understand the contribution of autophagy and the proteins involved in this process during specific viral infections.

Izabela A. Rodenhuis-Zybert, PhDAssociated Investigator within the Experimental Virology group of Professor Jolanda Smit

Izabela Rodenhuis-Zybert coordinates research lines that focus on innate immunity mechanisms triggered by mosquito-borne infections. They are particularly interested in 1) molecular pathogenesis of chikungunya virus-mediated arthralgia/arthritis and 2) the interplay of innate immune responses elicited during concurrent dengue virus and chikungunya virus infection.

John W.A. Rossen, PhDMedical Molecular Microbiologist, Principal Investigator Genomics for Infection Prevention and Head of the Molecular Unit of Medical Microbiology

John Rossen is Principal Investigator and head of the Molecular Unit within Medical Microbiology that implemented next generation sequencing for routine clinical microbiology and infection prevention. The method is used to determine the genetic relationship between pathogens and for molecular detection and further characterization of (emerging) pathogens, including analyses for revealing (new) antibiotic resistance mechanisms and determining the virulence of pathogens for improved risk assessment. Based on comparing whole genomes of bacteria, tailor-made diagnostic tests are developed for specific detection of outbreak and/or virulent bacterial strains. PhD students, postdocs and technicians work together to investigate samples from humans, animals, food and water.

Annelies Riezebos-Brilman, MD/PhDClinical Virologist, Medical Head of the Division of Clinical Virology, Principal Investigator Clinical Virology

Within the department of Medical Microbiology Annelies Riezebos-Brilman works as a consultant medical microbiologist with special interest in virology. In 2012 she was appointed Medical Head of the Division of Clinical Virology and Program Director (plaatsvervangend opleider) of Clinical Microbiology. Currently she also serves as chair of the Dutch Clinical Virology Study Group (NWKV) and she is chairperson of the Committee of Infection Prevention of the UMCG. Besides her clinical work she is involved in several clinical research projects mainly focusing on viral infections in solid organ transplant recipients. Her goal is to evaluate and improve direct patient care.

Chairs of the MHD Science Day

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© MMB Newsletter Special Edition 12.2015 • Medical Microbiology and Infection Prevention © MMB Newsletter Special Edition 12.2015 • Medical Microbiology and Infection Prevention

Welcome and introduction by Alex W. Friedrich

Session 1 Chair: F.M. Reggiori, PhD, Department of Cell Biology

Bacterial survival in sputum from intensive care unit patients

Jolien Seinen

Towards the design of personalized therapeutic vaccines against hepatitis C virus infection

Georgia Koutsoumpli

Social participation restrictions among former Buruli ulcer patients

Janine de Zeeuw

The fiscal consequences on cervical cancer prevention in Indonesia

Didik Setiawan

Session 2 Chair: I.A. Rodenhuis-Zybert, PhD, Experimental Virology

Unravelling the chikungunya virus cell entry pathways

Tabitha Hoornweg

Influence of size descriptors on drug exposure

Marieke Sturkenboom

Porphyromonas gingivalis – Comparative genomics and proteomics of an oral pathogen

Tim Stobernack

‘The flying Dutchman’; Five weeks in a mobile Ebola lab

Felix Geeraedts, MD/PhD (LabMicta)

Session 3 Chair: J.W.A. Rossen, PhD, Genomics for Infection Prevention

From the wound to the bench: co-existing bacteria interactions with Staphylococcus aureus exoproteome

Andrea García Perez

Virosomes delivering conserved viral proteins as a new universal influenza vaccine candidate

Dong Wei

Treatment after kidney transplantation: a delicate balance between BK virus infection and rejection?

Lilli Rurenga-Gard

Session 4 Chair: A. Riezebos-Brilman, MD/PhD, Clinical Virology

The resistant gut in our region

Xuewei Zhou

Development of a virosomal vaccine against Respiratory Syncytial Virus (RSV): Opportunities and challenges ahead

Julia Lederhofer

Health seeking behaviour and the impact of chikungunya and dengue disease in the Caribbean

Jelte Elsinga

Program of the Microbes in Health & Disease Science Day UMCG

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© MMB Newsletter Special Edition 12.2015 • Medical Microbiology and Infection Prevention © MMB Newsletter Special Edition 12.2015 • Medical Microbiology and Infection Prevention

Session 1 Fulvio M. Reggiori, chair of session 1

Jolien Seinen PhD student, Dept. Medical Microbiology Email: [email protected]

Research group:Molecular BacteriologyDepartment Genetics of Microorganisms, Interfaculty Institute for Genetics and Functional Genomics, Ernst Moritz Arndt University of Greifswald, Germany

Project:The main subject is “Bacterial Respiratory Infections – Common and Specific Mechanisms of Pathogen Adaptation and Immune Defense”, whereby this research project will mainly focus on Staphylococcus aureus and Streptococcus pneumoniae. Although carriage is usually non-symptomatic, they can become invasive causing a wide range of infections. One of these infections is pneumonia, especially in patients within the intensive care unit (ICU) of the hospital. The main question is: what causes the switch of these bacteria from being a commensal to a pathogen? In order to get the most realistic impression as possible on this issue, we’ll perform molecular analyses on sputum samples and clinical isolates from the ICU.

Key sentences/conclusions: The hypothesis is that bacteria behave and survive differently in human sputum than in laboratory growth media, as used in many research projects. To our knowledge, this research will be the first that includes real clinical sputum samples from ICU patients.

Bacterial survival in sputum from intensive care unit patients

Georgia Koutsoumpli PhD student, Dept. Medical Microbiology Email: [email protected]

Research group:Tumor Virology and Cancer Immunotherapy

Project:The PhD project focuses on the identification of targets for therapeutic vaccines against hepatitis C virus infection.A prerequisite for efficient hepatitis C virus (HCV) immunotherapies, including therapeutic immunization, is the induction of robust and broad-spectrum T-cell responses and immune memory against viral epitopes presented on infected cells.Since HCV infection is associated with viral escape mutants and HCV immunity seems strongly influenced by immune hierarchy, immunotherapy ideally should be tailor-made. We hypothesize that personalized vaccines, targeting multiple patient-specific HCV epitopes, will be more efficacious than vaccines targeting all HCV protein antigens.We aim to identify novel, mutated and/or subdominant HCV-specific epitopes by mass spectrometry. Based on their immunogenic potential, the identified epitopes could serve as targets for therapeutic vaccines against chronic HCV infection.

Key sentences/conclusions:We aim to identify HCV-specific epitopes by mass spectrometry to design personalized therapeutic vaccines against HCV infection.

Towards the design of personalized therapeutic vaccines against hepatitis C virus infection

Figure: Audience in the red auditorium

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© MMB Newsletter Special Edition 12.2015 • Medical Microbiology and Infection Prevention © MMB Newsletter Special Edition 12.2015 • Medical Microbiology and Infection Prevention

Session 2 Izabela A. Rodenhuis-Zybert, chair of session 2

Janine de Zeeuw Acting Assistant to the Dean, Learning Community Global HealthEmail: [email protected]

Research group:Department of Internal Medicine, Division of Infectious Diseases

Project:Janine has a BSc in Physiotherapy and a MSc in International Public Health. For her PhD project she has conducted quantita-tive and qualitative studies on pain and pain practices related to Buruli ulcer (BU). Furthermore, she has performed studies on social participation restrictions and the referral system of BU patients to specialized BU treatment centers.

Key sentences/conclusions: There are persisting participation restrictions in almost half of the former patients with BU in Ghana and Benin. The areas in which former BU patients experienced restrictions differed between Ghana and Benin. Predictors of participation restrictions were sex, perceived stigma, functional limitations and the size of the lesion.

Social participation restrictions among former Buruli ulcer patients

Didik Setiawan PhD student Research Institute of Pharmacy Email: [email protected]

Research group:Pharmacoepidemiology and Pharmacoeconomics

Project:Cervical cancer is one of the main burdens in developing countries including Indonesia. Human papilloma virus (HPV) vacci-nation and screening are the main prevention strategies promoted by the World Health Organization (WHO). Thus, monetary consideration is still the main issue for the government on implementing health technology policy. This study implemented generational accounting theory to explore the consequences of cervical cancer prevention strategy implementation on Indonesian governments’ revenue and expenses. According to governments’ perspective, HPV vaccination in combination with cervical screening is the most beneficial option for cervical cancer prevention strategies in Indonesia (Net Present Value (NPV) I$2.212.310.012), followed by HPV vaccination (NPV I$2.026.113.405) and cervical screening alone (NPV I$408.584.210).

Key sentences/conclusions: • Cervical cancer is a serious burden for developing countries including Indonesia• HPV vaccine and cervical screening are clinically proven• Fiscal consideration is an important consideration for the government• According to governments’ perspective, the combination of HPV vaccination and cervical screening is the most beneficial followed by HPV vaccination alone and cervical screening alone.

The fiscal consequences on cervical cancer prevention in Indonesia

Tabitha Hoornweg PhD student, Dept. Medical Microbiology Email: [email protected]

Research group:Experimental Virology

Project:In the Experimental Virology lab we study arthropod-borne alpha- and flaviviruses, such as chikungunya virus (CHIKV) and dengue virus (DENV). In my research project, I mainly focus on the cell entry pathway these viruses use to infect their host cells. The technique to fluorescently label single DENV virions and track these virions during cell entry is established in our lab. Recently, we adapted this technique to fluorescently label and track CHIKV. Using this technique we can study cell entry kinetics and follow the interactions of the virus and host cell proteins during virus cell entry.

Key sentences/conclusions: We were able to track single fluorescently-labelled chikungunya virions in live cells. Using this technique we showed CHIKV cell entry is a very fast process, which almost completely takes place in the first 20 minutes of infection. CHIKV was found to mainly enter its host cell via clathrin-mediated endocytosis. Furthermore, CHIKV fusion was shown to occur from within the mildly acidic early endosomes.

Unravelling the chikungunya virus cell entry pathways

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© MMB Newsletter Special Edition 12.2015 • Medical Microbiology and Infection Prevention © MMB Newsletter Special Edition 12.2015 • Medical Microbiology and Infection Prevention

Marieke Sturkenboom Hospital Pharmacist, Dept. of Clinical Pharmacy and PharmacologyEmail: [email protected]

Research group:Tuberculosis Group

Project:Isoniazid and rifampin are first-line anti-tuberculosis drugs that are dosed on total body weight (TBW). Malnutrition is often seen in tuberculosis (TB) patients and may lead to underdosing. The goal of this study was to determine the influence of different variables on drug exposure of isoniazid and rifampin in TB patients.We conducted a retrospective study of patients with drug-susceptible TB treated with isoniazid or rifampin and for whom an area under the concentration-time curve over 24 hours (AUC

0-24) of either isoniazid or rifampin was available. We collec-

ted demographic, clinical, and biochemical data through review of the medical records. The correlation of clinical variables with drug exposure was determined.

Key sentences/conclusions: 66 TB patients met the inclusion criteria. Univariate analysis showed no association between isoniazid dose/TBW and ex-posure (adjusted R2=0.008, P=.232). A small, but significant positive association was shown between rifampin dose/TBW and exposure (adjusted R2=0.102, P=.006), and between sex and exposure (adjusted R2=0.194, P<.001). Multiple linear regression analysis showed a significant, small, independent, and positive association of isoniazid AUC

0-24 with the dose/

TBW, body mass index (BMI), alanine aminotransferase, gamma-glutamyl transferase, and high C-reactive protein (CRP) level (adjusted R2=0.228, P=.005). A significant, independent, and positive association of rifampin AUC

0-24 was shown with

the dose/TBW, sex, BMI, and CRP level (adjusted R2=0.354, P<.001). Isoniazid dose/TBW is not associated with its exposure in drug susceptible TB patients. Rifampin dose/TBW and sex are associated with rifampin exposure but have limited influence.

Influence of size descriptors on drug exposure

Tim Stobernack PhD student, Dept. Medical MicrobiologyEmail: [email protected]

Research group:Molecular Bacteriology

Project:Autoimmune diseases are commonly encountered throughout the world, but their exact triggers are still unknown. One theory proposes that autoimmunity is triggered by bacterial infections. Significant correlations between oral bacterial infections (e.g. periodontitis) and the autoimmune disease rheumatoid arthritis (RA) have been shown, but the precise mechanism remains undefined.The project aims to determine the impact of the oral pathogen Porphyromonas gingivalis on the host immune system with a special focus on the role of citrullination and proteolysis by P. gingivalis and their effects on host immunity. Recent studies showed that P. gingivalis produces several virulence factors, including the citrullinating enzyme peptidylarginine deiminase (PPAD) and cysteine proteases called gingipains. Since these proteins are apparently secreted, we hypothesize that their interactions with the host immune system could trigger autoimmunity.

Key sentences/conclusions: • Genetic variance in virulence factor genes was observed between isolates, especially in attachment- and capsule-related genes• Differences were observed in protein secretion and citrullination between clinical P. gingivalis isolates• Peptidylarginine deiminase (PPAD) was detected in gum tissues of periodontitis and RA patients, especially around the blood vessels• P. gingivalis gets internalized by neutrophils and macrophages and citrullinates host proteins• P. gingivalis PPAD could cause hypercitrullination of neutrophil extracellular traps (NETs)

Porphyromonas gingivalis – Comparative genomics and proteomics of an oral pathogen

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© MMB Newsletter Special Edition 12.2015 • Medical Microbiology and Infection Prevention © MMB Newsletter Special Edition 12.2015 • Medical Microbiology and Infection Prevention

Session 3 John W.A. Rossen, chair of session 3

Andrea García Perez PhD student, Dept. Medical MicrobiologyEmail: [email protected]

Research group:Molecular Bacteriology

Project:The study of pathogenic bacteria, either in vitro or with animal models, is commonly regarded on the basis of bacteria as secluded species. The present study considers the microbiome of the chronic wounds in patients with Epidermolysis Bullosa (EB)– a genetic disease characterized by chronic wounds upon simple mechanical trauma. Particularly, we focus on the interactions of Staphylococcus aureus with other microbes due to its high prevalence in the chronic wounds. Therefore, using a broad analytical approach through mass spectrometry we explore the inherent relationships between the exoproteome of S. aureus and that of the coexisting bacteria in the same wound.

Key sentences/conclusions: • Phenotypic differences between S. aureus strains correlate with the observed exoproteome differences• S. aureus seems to benefit from the biological processes of other microbes• The exoproteome variations among cultures suggest that adaptive mechanisms differ in all strains

From the wound to the bench: co-existing bacteria interactions with Staphylococcus aureus exoproteome

Figure: Break in the blue patio

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© MMB Newsletter Special Edition 12.2015 • Medical Microbiology and Infection Prevention © MMB Newsletter Special Edition 12.2015 • Medical Microbiology and Infection Prevention

Wei Dong PhD student, Dept. Medical MicrobiologyEmail: [email protected]

Research group:Vaccinology

Project:Influenza A virus infections continue to be one of the biggest burdens for human health because of the capability of influenza virus to cause epidemics and pandemics. Vaccines help in infection control, however, due to antigenic shift and antigenic drift of the virus, antibodies cannot provide protection to unmatched influenza viruses. Therefore, influenza vaccines which can induce cross-protective immunity to different strains of influenza virus are urgently needed. CD8+ T cells that are specific to conserved internal influenza antigen, such as nucleoprotein (NP), are not influenced by mutated surface protein and could therefore play an important role in cross-protective immunity.

Key sentences/conclusions: In this study we construct modified influenza virosomes with the incorporated adjuvant monophosphoryl lipid A (MPLA) and attached NP. While the incorporation of MPLA to virosome can increase the maturation of antigen presenting cells (APCs), the attachment of NP to virosomes can enhance the uptake of NP by APCs. Both of these two approaches have the potential to enhance the induction of CD8+ T cells. In an in vivo experiment, these modified virosomes induced cross-protective immunity to a different strain of virus. Taken together, modified influenza virosomes can be used as a candidate for a universal influenza vaccine.

Virosomes delivering conserved viral proteins as a new universal influenza vaccine candidate

Lilli Rurenga-Gard Section Manager Clinical Virology / PhD student, Dept. Medical MicrobiologyEmail: [email protected]

Research group:(Department of Medical Microbiology, Division of) Clinical VirologyDepartment of Internal medicine, Division of Nephrology

Project:Polyomavirus BK (BKV) can cause nephropathy in renal transplant recipients. Primary infections tend to occur early in childhood and after infection BKV remains latent in the reno-urinary tract. Reactivation is found in up to 80% of renal transplant recipients and in 1-7% BKV associated nephropathy (BKVAN) develops. One of the most commonly described risk factors is the introduction of new immunosuppressive drugs. Until now no effective antiviral therapy exists for BKV and reduction of the immunosuppression is recommended to control the BKV replication, with the disadvantage of increased risk of rejection.

Key sentences/conclusions: Triple immunosuppressive therapy with prednisolone, mycophenolic acid and tacrolimus is associated with a low incidence of allograft rejection, but is associated with a higher incidence of BKVAN. We retrospectively investigated the frequency of BK virus complications in a cohort of 359 renal transplant recipients treated with mycophenolate mofetil or mycophenolic acid with either cyclosporine A (CsA) or tacrolimus (Tac) with or without prednisolone, with two years of follow-up. In our cohort BKVAN occurred more often in the Tac group (6.4%) versus the CsA group (2.1%) (p=0.04). However, the incidence of rejection was significantly higher in the CsA (19.5%) compared to the Tac (11.2%) (p=0.03) group. This study shows that immunosuppressive treatment with Tac is associated with a lower incidence of rejection, but possibly at the cost of an increased risk of developing BKVAN in the first two years post-transplantation.

Treatment after kidney transplantation: a delicate balance between BK virus infection and rejection?

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Session 4 Annelies Riezebos – Brilman, chair of session 4

Xuewei Zhou PhD student/MD, Clinical microbiologist in training, Dept. Medical MicrobiologyEmail: [email protected]

Research group:Genomics for Infection Prevention

Project:Enterococcus faecium and VRE (vancomycin resistant enterococci) are a growing problem in hospitals. This project focuses on epidemiology, diagnostics and treatment of E. faecium infection and colonization.

Key sentences/conclusions: For this research we focused on the epidemiology of E. faecium and ESBL (extended spectrum betalactamase) producing bacteria in the community as well as in hospitals. The conclusion is that E. faecium is a true nosocomial pathogen, while ESBL producing bacteria can be acquired in hospitals as well as in the community.

The resistant gut in our region

Julia Lederhofer PhD student, Dept. Medical MicrobiologyEmail: [email protected]

Research group:Vaccinology

Project:Respiratory syncytial virus (RSV) is the most common cause of viral bronchiolitis in infants and young children worldwide and also causes serious disease in elderly and immunocompromised individuals. Despite its impact on global health, there is no vaccine available for prevention of RSV infection. RSV is an enveloped, negative-sense single stranded RNA virus, which forms polymorphic particles ranging from filamentous (up to 1µm in size) to spherical (with a diameter of 50-300 nm).We are in late preclinical development of an RSV vaccine candidate which contains reconstituted viral envelopes (virosomes) with a built-in monophosphoryl lipid A (MPLA) adjuvant, which is a Toll-like receptor-4 (TLR4) agonist. RSV virosomes are produced by solubilisation of the envelope of purified RSV with DCPC (a detergent-like phospholipid), removal of the nucleocapsid by ultracentrifugation, and subsequent reconstitution of viral envelopes, containing the F and G viral glyco-proteins, through dialysis of DCPC.

Key sentences/conclusions: • The vaccine, developed for elderly, against RSV should optimize and boost virus neutralizing activity• Virosomes were characterized and shown to be successfully reconstituted and spherical with a size distribution of 60-140 nm• The sites that elicit the most potent neutralizing (NT) antibodies are only present on prefusion F• Incorporation of the adjuvant MPLA into the virosomes significantly increases the NT antibody titers The antibody response is dose dependent on the concentration of the adjuvant MPLA incorporated in the virosomes

Development of a virosomal vaccine against respiratory syncytial virus (RSV): Opportunities and challenges ahead

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Jelte Elsinga MD/PhD student, Dept. Medical MicrobiologyEmail: [email protected]

Research group:Genomics for Infection Prevention

Project:Dengue and chikungunya disease are important infectious diseases for the Americas. Preventing and treating these diseases remains a chal-lenge. To understand and improve health seeking behaviour, we set up two projects in Venezuela and Curaçao.

Key sentences/conclusions: • Health seeking behaviour is an important topic for regions endemic for dengue• Intentions to seek medical help differ between fever and suspected dengue, and between children and adults in the case of dengue• In the case of a suspected dengue infection people intended to seek medical help earlier. Aid in diagnosing dengue at home (self- diagnosing tool) may enhance early health centre attendance.• Raising awareness and risk perception of dengue may improve immediate health centre attendance• People with a past dengue infection are more probable to initially treat a consecutive infection at home. Since this group has a higher chance of severe dengue disease, efforts have to be made to promote immediate health centre attendance in this group.

Health seeking behaviour and the impact of chikungunya and dengue disease in the Caribbean

Alex W. FriedrichChair of Medical Microbiology and Infection Prevention

Head of DepartmentUniversity Medical Center Groningen

Tel: +31.(0)50.361 3480

[email protected]

This newsletter is published by the Department of Medical Microbiology and Infection Prevention of the University Medical Center Groningen.The editorial staff consists of: Alex W. Friedrich, Carolien Doorenbos and Edwina Doting.

[email protected]@[email protected]

The editors especially thank Mehdi Sadaghian Sadabad and Jolanda Oldengarm -Leidelmeijer for the nice pictures that illustrate this newsletter.

© Design/Realisation IDEART-Agentur.de

Impressum

How can we be contacted?

Secretariat MMB (050 36) 13480Email [email protected]

Laboratory administration:

bacteriology (050 36) 13589virology (050 36) 15184

Consultants (during office hours):

bacteriology pager 77856 / 77857virology pager 77830infection prevention 55141

Consultants (out-of-hours):

on call clinical microbiologist through receptionist: 050-3616161 / 92222

on call clinical virologist through receptionist

on call infection prevention expert through receptionist

Website www.mmb-umcg.nl

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