Infeksjonssykdommer – forskningsgruppe

Dette er en virussykdom som angriper leveren og tar 1 million liv hvert år. En enkel tablettbehandling hindrer utvikling av leversykdom, men slik behandling må i utgangspunktet tas livet ut.

I Nuc-Stop-studien, undersøker vi om det å slutte med behandling kan sette i gang en gunstig immunrespons og fjerne hepatitt B-viruset for godt. Totalt 11 sykehus i Norge, Sverige, Danmark og Etiopia deltar i studien, som er ledet av Asgeir Johannessen. Resultatene fra denne studien vil kunne spare mange pasienter for livslang behandling, og vil gi en uvurderlig innsikt i de immunologiske mekanismene ved kronisk hepatitt B.

I fattige land er behandling av hepatitt B utilgjengelig for de fleste. I studien Chronic hepatitis B: improving care and scaling up treatment in sub-Saharan Africa vil Asgeir Johannessen og kollegaer i Etiopia bane vei for enklere og rimeligere behandling i fattige land. Studien er et norsk-etiopisk samarbeid hvor man håper å kunne bringe hepatitt B under kontroll i Afrika. Dette skal oppnås ved å ta i bruk ny teknologi for å enklere påvise hvem som trenger behandling, og samtidig forenkle og strømlinjeforme retningslinjer.   

Urinveisinfeksjoner er blant de vanligste infeksjonene som fører til foreskrivning av antibiotika. Dermed er det også en stor potensiell gevinst dersom leger skriver ut de minst resistens-drivende typene antibiotika.
I MePUR-studien, som ledes av Tore Stenstad, har vi undersøkt effekten av det smalspektrede midlet mecillinam hos innlagte pasienter med øvre urinveisinfeksjon og vekst av E.coli i blodet. Pasientene fikk standard intravenøs antibiotika i 3 døgn før overgang til mecillinam tabletter. Analyser av kliniske utfall i denne studien er underveis. Vi har også kartlagt hvordan høydosert mecillinam påvirker konsentrasjonen av karnitin i blodet. I tillegg er det høstet biologisk materiale som gir oss mulighet til analysere bakterienes genetiske profil samt å kartlegge pasientenes betennelsesrespons.  

Vi deltar i flere eksternt initierte behandlingsstudier på COVID-19. I 2020 inkluderte vi pasienter i den internasjonale SOLIDARITY-studien, der vi fant at verken hydroksyklorokin eller remdesivir gir noen bedret overlevelse ved COVID-19. I 2021 deltar vi i SolidAct-studien, en randomisert kontrollert multisenterstudie på effekten av baricitinib ved alvorlig COVID-19. I en regional multisenterstudie inkluderes pasienter som i perioden mars-20 til februar-21 har vært respiratorbehandlet for å se om det er forskjeller i bakterielle infeksjoner før og etter at steroider ble innført som standardbehandling. 

Asgeir Johannessen (forskningsgruppeleder)

Bjørn Åsheim-Hansen

Jonas Iversen

Stian MS Orlien

Hailemichael Desalegn

Contagious diseases have always been a threat to our health and welfare, which the recent pandemic has clearly showed us. In order to face a constantly changing panorama of infectious diseases we need better treatment, improved methods to detect microorganisms, and more precise tools to identify disease. 

We have selected three main priorities for 2021-2024:

1. ​Hepatitis B
2. Correct use of antibiotics
   
3. COVID-19

For more information, please contact the group leader Asgeir Johannessen MD PhD (asgeir.johannessen@siv.no) ​
​

IMPACT-B: Immunization to protect African children from transmission of hepatitis B. Prosjektleder: Shevanthi Nayagam, Imperial College London, UK.

Hepatitis B in sub-Saharan Africa collaborative network (HEPSANET). Prosjektleder: Asgeir Johannessen, Sykehuset i Vestfold.

​Personalised treatment and care for chronic hepatitis B. Prosjektleder: Dag Henrik Reikvam, Oslo universitetssykehus.

EU-SolidAct - Baricitinib. En randomisert kontrollert multisenterstudie av pasienter med COVID-19 på sykehus Prosjektleder: Alexander Rygh Holten, Oslo universitetssykehus

Chronic hepatitis B: improving care and scaling up treatment in sub-Saharan Africa.
Prosjektleder: Asgeir Johannessen, Sykehuset i Vestfold

Super-infections i​n Covid-19 patients in the ICU – before and after dexamethasone​
Prosjektleder: Ingvild Nordøy, OUS

Tick-borne encephalitis in humans in Norway
Prosjektleder:​ Hege Kersten, Sykehuset i Telemark

The NOR Solidarity multicenter trial on the efficacy of different anti-viral drugs in SARS CoV-2 infected patients​
​Prosjektleder: An​dreas Barratt-Due, Oslo universitetssykehus

Norwegian Nucleoside Analogue Stop Study (Nuc-Stop)​​
​Prosjektleder: Asgeir Johannessen, Sykehuset i Vestfold

The human small intestinal microbiota​
PhD-prosjekt for Heidi Villmones. Prosjektleder: Tore Stenstad, SiV

Etterbehandling av nyrebekkenbetennelse med tabletter​
Pros​jektleder: Tore Stenstad, SiV

Behandling av hepatitt B i fattige land: et pilotprosjekt i Etiopia og Somaliland​​
​Prosjektleder: Asgeir Johannesse​n, SiV

2022

• Vestad B, Ueland T, Lerum T, Dahl TB, Holm K, Barratt-Due A, Kåsine T, Dyrhol-Riise AM, Stiksrud B, Tonby K, Hoel H, Olsen IC, Henriksen KN, Tveita A, Manotheepan R, Haugli M, Eiken R, Berg Å, Halvorsen B, Kildal AB, Johannessen A, et al. Respiratory dysfunction three months after seve​re COVID-19 is associated with gut microbiota alterations. J Intern Med 2022;291(6):801-812.
• WHO Solidarity Trial Consortium. Remdesivir and three other drugs for hospitalized patients with Covid-19: final results of the WHO Solidarity randomized trial and updated meta-analyses. Lancet 2022;399:1941-1953.
• Villmones HC, Svanevik M, Ulvestad E, Stenstad T, Anthonisen IL, Nygaard RM, Dyrhovden R, Kommedal Ø. Investigating the human jejunal microbiota. Sci Rep 2022;12:1682.
• Søvik S, Barratt-Due A, Kasine T, Olasveengen T, Strand MW, Tveita AA, Berdal JE, Lehre MA, Lorentsen T, Heggelund L, Stenstad T, Ringstad J, Müller F, Aukrust P, Holter JC, Nordoy I. Corticosteroids and superinfections in COVID-19 patients on invasive mechanical ventilation. J Infect 2022;85(1):57-63.
• Hansen BÅ, Grude N, Lindbæk M, Stenstad T. The efficacy of pivmecillinam in oral step-down treatment in hospitalized patients with E.coli bacteremic urinary tract infection; a single-arm, uncontrolled treatment study. BMC Infect Dis 2022;22:478.
• Tønnessen R, García I, Debech N, Lindstrøm JC, Wester AL, Skaare D. Molecular epidemiology and antibiotic resistance profiles of invasive Haemophilus influenzae from Norway 2017–2021. Front Microbiol 2022;13:973257.
• Johannessen H, Anthonisen IL, Zecic N, Hegstad K, Ranheim TE, Skaare D. Characterization and Fitness Cost of Tn7100, a Novel Integrative and Conjugative Element Conferring Multidrug Resistance in Haemophilus influenzae. Front Microbiol 2022;13:945411.
• Lindemann PC, Mylvaganam H, Oppegaard O, Anthonisen IL, Zecic N, Skaare D. Case Report: Whole-Genome Sequencing of Serially Collected Haemophilus influenzae From a Patient With Common Variable Immunodeficiency Reveals Within-Host Evolution of Resistance to Trimethoprim-Sulfamethoxazole and Azithromycin After Prolonged Treatment With These Antibiotics. Front Cell Infect Microbiol 2022;12:896823.
• Spearman CW, Dusheiko G, Jonas E, Abdo A, Afihene M, Cunha L, Desalegn H, et al. Hepatocellular carcinoma: measures to improve the outlook in sub-Saharan Africa. Lancet Gastroenterol Hepatol 2022:S2468-1253(22)00041-3.
• Tassachew Y, Abebe T, Belyhun Y, Teffera T, Shewaye AB, Desalegn H, et al. Prevalence of HIV and Its Co-Infection with Hepatitis B/C Virus Among Chronic Liver Disease Patients in Ethiopia. Hepat Med 2022;14:67-77.
• Desai AN, Mohareb AM, Elkarsany MM, Desalegn H, Madoff LC, Lassmann B. Viral Hepatitis E Outbreaks in Refugees and Internally Displaced Populations, sub-Saharan Africa, 2010-2020. Emerg Infect Dis 2022;28(5):1074-1076.
• Fouad Y, Dufour JF, Zheng MH, Bollipo S, Desalegn H, Grønbaek H, Gish RG. The NAFLD-MAFLD debate: Is there a Consensus-on-Consensus methodology? Liver Int 2022;42(4):742-748.
• Desalegn H, Tesfaye A, Shume P. Pyogenic Liver Abscess Presenting as an Initial Manifestation of Underlying Hepatocellular Cancer: A Case Report in Ethiopia. Ethiop J Health Sci 2022;32(3):665-668. ​
  

2021

• ​Barratt-Due A, Olsen IC, Henriksen KN, Kåsine T, Lund-Johansen F, Hoel H, Holten AR, Tveita A, Mathiessen A, Haugli M, Eiken R, Kildal B, Berg Å, Johannessen A, et al. Evaluation of remdesivir and hydroxychloroquine on viral clearance in Covid-19: Results from a randomized trial. Ann Intern Med 2021;174:1261-1269.
• WHO Solidarity Trial Consortium. Repurposed antiviral drugs for Covid-19 – Interim WHO Solidarity Trial Results. N Engl J Med 2021;384:497-511.
• Lerum TV, Maltzahn NN, Aukrust P, Trøseid M, Henriksen KN, Kåsine T, Dyrhol-Riise AM, Stiksrud B, Haugli M, Blomberg B, Kittang BR, Johannessen A, et al. High prevalence of persistent pulmonary pathology in COVID-19 patients three months after hospital admission is associated with disease severity: potential role of matrix degradation. A NOR-Solidarity sub-study. Sci Reports 2021;11:23205.
• Orlien SMS, Ahmed TA, Ismael NY, Berhe NB, Bakken-Kran AM, Gundersen SG, Johannessen A. Field performance of HBsAg rapid diagnostic tests in rural Ethiopia. J Virol Methods 2021;289:114061.
• Villmones HC, Halland A, Stenstad T, Ulvestad E, Weedon-Fekjær H, Kommedal Ø. The cultivable microbiota of the human distal ileum. Clin Microbiol Infect 2021;27:912.e7-912.e13..
• Johannessen A, Mekasha B, Desalegn H, Aberra H, Stene-Johansen K, Berhe N. Mother-to-child transmission of hepatitis B virus in Ethiopia. Vaccines 2021;9:430.
• Woldemedihn GM, Rueegg CS, Desalegn H, Aberra H, Berhe N, Johannessen A. Validity of a point-of-care viral load test for hepatitis B in a low-income setting. J Virol Methods 2021;289:114057.
• Antonelli G, Karsensten JG, Bhat P, Ijoma U, Osuagwu C, Desalegn H, Abera H, Guy C, Vilmann P, Dinis-Ribeiro M, Ponchon T, Sabbagh LC, Pausawasdi N, Makharia G, Hassan C, Veitch A, Aabakken L, Ebigbo A; Endoscopy and COVID-19 Cascade Working Group, European Society of Gastrointestinal Endoscopy, World Endoscopy Organization and World Gastroenterology Organization. Resuming endoscopy during COVID-19 pandemic: ESGE, WEO and WGO Joint Cascade Guideline for Resource Limited Settings. Endosc Int Open 2021;9(4):E543-E551.
• Spearman CW, Desalegn H, Ocama P, Awuku YA, Ojo O, Elsahhar M, Abdo AA, Ndububa DA, Fouad Y, Borodo MM, Ng'wanasayi M, Ally R, Elwakil R. The sub-Saharan Africa position statement on the redefinition of fatty liver disease: From NAFLD to MAFLD. J Hepatol 2021;74(5):1256-1258.
• Fisseha H, Desalegn H. Perception of students and examiners about objective structured clinical examination in a teaching hospital in Ethiopia. Adv Med Educ Pract 2021;12:1439-1448.
• Mwachiro M, Topazian HM, Kayamba V, Mulima G, Ogutu E, Erkie M, Lenga G, Mutie T, Mukhwana E, Desalegn H, Berhe R, Meshesha BR, Kaimila B, Kelly P, Fleischer D, Dawsey SM, Topazian MD. Gastrointestinal endoscopy capacity in Eastern Africa. Endosc Int Open 2021;9:E1827-E1836.
• Cordie A, Mohamed R, Sonderup MW, Wendy Spearman C, Medhat MA, Debzi N, Desalegn H, Esmat G. Hepatitis C elimination in Africa: seizing the moment for hepatitis C-free future. Arab J Gastroenterol 2021;22:249-251.
• Bhat P, Hassan C, Desalegn H, Aabakken L.. Promotion of gastrointestinal endoscopy in sub-Saharan Africa: what is needed, and how can ESGE and WEO help? Endosc Int Open 2021;9:E1001-E1003. ​

​2020

• Hjelmesæth J, Skaare D. Loss of smell or taste as the only symptom of COVID-19. Tidsskr Nor Laegeforen 2020;140(7).
• Hegstad K, Mylvaganam H, Janice J, Josefsen E, Sivertsen A, Skaare D. Role of Horizontal Gene Transfer in the Development of Multidrug Resistance in Haemophilus influenzae. mSphere 2020;5(1):e00969-19.
• Ebigbo A, Karstensen JG, Bhat P, Ijoma U, Osuagwu C, Desalegn H, Oyeleke GK, Gebru RB, Guy C, Antonelli G, Vilmann P, Aabakken L, Hassan C. Impact of the COVID-19 pandemic on gastrointestinal endoscopy in Africa. Endosc Int Open 2020;8(8):E1097-E1101.
• Memirie ST, Desalegn H, Naizgi M, Nigus M, Taddesse L, Tadesse Y, Tessema F, Zelalem M, Girma T. Introduction of birth dose of hepatitis B virus vaccine to the immunization program in Ethiopia: an economic evaluation. Cost Eff Resour Alloc 2020;18:23.
• Karstensen JG, Ebigbo A, Bhat P, Dinis-Ribeiro M, Gralnek I, Guy C, Le Moine O, Vilmann P, Antonelli G, Ijoma U, Anigbo G, Afiheni M, Duduyemi B, Desalegn H, De Franchis R, Ponchon T, Hassan C, Aabakken L. Endoscopic treatment of variceal upper gastrointestinal bleeding: European Society of Gastrointestinal Endoscopy (ESGE) Cascade Guideline. Endosc Int Open 2020;8(7):E990-E997.
• Gupta N, Desalegn H, Ocama P, Lacombe K, Njouom R, Afihene M, Cunha L, Spearman CW, Sonderup MW, Kateera F. Converging pandemics: implications of COVID-19 for the viral hepatitis response in sub-Saharan Africa. Lancet Gastroenterol Hepatol 2020;5(7):634-636.
• Gupta N, Kateera F, Desalegn H, Ocama P, Njouom R, Lacombe K. Is resistance to direct-acting antivirals in sub-Saharan Africa a threat to HCV elimination? Recommendations for action. J Hepatol 2020;72(3):583-584.
• Sonderup MW, Dusheiko G, Desalegn H, Lemoine M, Tzeuton C, Taylor-Robinson SD, Spearman CW. Hepatitis B in sub-Saharan Africa-How many patients need therapy? J Viral Hepat 2020;27(6):560-567.
• Fisseha H, Mulugeta W, Kassu RA, Geleta T, Desalegn H. Perspectives of Protocol Based Breaking Bad News among Medical Patients and Physicians in a Teaching Hospital, Ethiopia. Ethiop J Health Sci 2020;30(6):1017-1026.
• Desalegn H, Chanie Y, Shume P, Delil M, Gupta N, Johannessen A. Assessment of non-invasive fibrosis markers in patients with chronic hepatitis C in Ethiopia. Clin Liver Dis 2020;16:168-172.

2019​

• Hesstvedt L, Gaustad P, Müller F, Andersen CT, Brunborg C, Mylvaganam H, Leiva RA, Berdal JE, Ranheim TE, Johnsen BO, Falch BM, Grimnes G, Skogen V, Haarr E, Lyngøy AS, Larssen KW, Hannula R, Hansen BÅ, Nordøy I & the Norwegian Fungal Network. The impact of age on risk assessment, therapeutic practice and outcome in candidemia. Infectious Diseases 2019;51(6):425-434
• Skaare D: Pasteurellaceae. In: Medisinsk mikrobiologi. Edited by Rollag H, Müller F, Tønjum T. Oslo: Gyldendal Akademisk; 2019. ISBN 978-82-05-50098-3.
• Aberra H, Desalegn H, Berhe N, Mekasha B, Medhin G, Gundersen SG, Johannessen A. The WHO guidelines for chronic hepatitis B fail to detect half of the patients in need of treatment in Ethiopia.J Hepatol 2019;70:1065-71.
• Orlien SMS, Berhe NB, Morgan MY, Johannessen A. Khat-related liver disease in sub-Saharan Africa: neglected, yet important.Lancet Glob Health 2019;7(3):e310. 
• Desalegn H, Aberra H, Berhe N, Medhin G, Mekasha B, Gundersen SG, Johannessen A. Predictors of mortality in patients under treatment for chronic hepatitis B in Ethiopia: a prospective cohort study.BMC Gastroenterology 2019;19:74.
• Johannessen A, Aberra H, Desalegn H, Gordien E, Berhe N. A novel score to select patients for treatment in chronic hepatitis B: results from a large Ethiopian cohort. J Hepatol 2019;71:840-41.
• Al-Shudifat AE, Azab M, Johannessen A, Agraib LM, Tayyem RF. Is the intake of antioxidants associated with risk of coronary artery disease? A Jordanian case-control study.Top Clin Nutr 2019;34:259-268.

2018​

• Villmones HC, Haug ES, Ulvestad E, Grude N, Stenstad T, Halland A, Kommedal Ø. Species Level Description of the Human Ileal Bacterial Microbiota. Sci Rep 2018;8(1):4736.
• Aberra H, Gordien E, Desalegn H, Berhe N, Medhin G, Mekasha B, Gundersen SG, Gerber A, Stene-Johansen K, Øverbø J, Johannessen A. Hepatitis delta infection in a large cohort of chronic hepatitis B patients in Ehiopia.Liver Int 2018;38(6):1000-1009.
• Tayyem RT, Al-Shudifat AE, Johannessen A, Bawadi HA, AbuMweis SS, Agraib LM, Allhedan SS, Haj-Husein I, Azab M. Dietary patterns and the risk of coronary heart disease among Jordanians: A case-control study.Nutr Metab Cardiovasc Dis 2018;28:262-9.
• Orlien SMS, Ismael NY, Ahmed TA, Berhe NB, Lauritzen T, Roald B, Goldin RD, Stene-Johansen K, Dyrhol-Riise AM, Gundersen SG, Morgan MY, Johannessen A. Unexplained chronic liver disease in Ethiopia: a cross-sectional study.BMC Gastroenterol 2018;18:27.
• Al-Shudifat AE, Azab M, Johannessen A, Al-Shdaifat A, Agraib LM, Tayyem RF. Elevated fasting blood glucose, but not obesity, is associated with coronary artery disease in patients undergoing elective coronary angiography in Jordan.Ann Saudi Med 2018;38(2):111-117.
• Orlien SMS, Sandven I, Morgan MY, Berhe NB, Ismael NY, Ahmed TA, Stene-Johansen K, Gundersen SG, Johannessen A. Khat chewing increases the risk for developing chronic liver disease: a hospital-based case-control study.Hepatology 2018;68(1):248-257.
• Azab M, Al-Shudifat AE, Johannessen A, Al-Shdaifat A, Agraib LM, Tayyem RF. Are risk factors for coronary artery disease different in persons with and without obesity?Metab Syndr Relat Disord 2018;16(8):440-445.
• Desalegn H, Aberra H, Berhe N, Mekasha B, Stene-Johansen K, Krarup H, Pereira AP, Gundersen SG, Johannessen A. Treatment of chronic hepatitis B in sub-Saharan Africa: one-year results of a pilot treatment program.BMC Medicine 2018;16:234.
• Orlien SMS, Ahmed TA, Ismael NY, Berhe NB, Lauritzen T, Gundersen SG, Johannessen A. High seroprevalence of autoantibodies typical of autoimmune liver disease in eastern Ethiopia: is chewing of khat (Catha edulis) a triggering factor?Can J Gastroenterol Hepatol 2018:4980597.

2017

• Skaare D. Betalaktamresistens hos Haemophilus influenzae. Tidsskr Nor Laegeforen 2017;137(6):471.
• Månsson V, Skaare D, Riesbeck K, Resman F.The spread and clinical impact of ST14CC-PBP3 type IIb/A, a clonal group of non-typeable Haemophilus influenzae with chromosomally mediated β-lactam resistance-a prospective observational study. Clin Microbiol Infect 2017;23(3):209.e1-209.e7.
• Desalegn H, Aberra H, Berhe N, Gundersen SG, Johannessen A. Are non-invasive fibrosis markers for chronic hepatitis B valid in sub-Saharan Africa?Liver Int 2017;37(10):1461-7.
• Desalegn H, Johannessen A. Response to Non-invasive fibrosis markers for chronic hepatitis B in sub-Saharan Africa.Liver Int 2017;37(11):1739.
• Al-Shudifat AE, Al-Shdaifat A, Al-Abdouh AA, Aburoman MI, Otoum SM, Sweedan AG, Khrais I, Abdel-Hafez IH, Johannessen A. Diabetes risk score in a young student population in Jordan – a cross-sectional study.J Diab Res 2017;2017:8290710.
• Aberra H, Desalegn H, Berhe N, Medhin G, Stene-Johansen K, Gundersen SG, Johannessen A. Early experiences from one of the largest treatment programs for chronic hepatitis B in sub-Saharan Africa.BMC Infect Dis 2017;17(1):438.
• Al-Shudifat AE, Johannessen A, Azab M, Al-Shdaifat A, AbuMweis SS, Agraib LM, Tayyem RF. Risk factors for coronary artery disease in patients undergoing elective coronary angiography in Jordan. BMC Cardiovasc Disord 2017: 17(1):183.

Nasjonalt

1. Senter for eliminasjon av hepatitt C​ (SELIHEP)
   
2. Akershus universitetssykehus: Olav Dalgard (Nuc-Stop-studien).
3. Oslo universitetssykehus: Dag Henrik Reikvam (Nuc-Stop-studien) og Alexander Rygh Holten og Andreas Barratt-Due (COVID-19-studier).
4. Sykehuset i Telemark: Hege Kersten.
   

Internasjonalt

1. Imperial College London, UK​
   
2. St. Paul's Hospital Millennium Medical College, Etiopia
3. Addis Ababa University, Etiopia
4. Karolinska universitetssjukhuset, Sverige
5. Hvidovre Hospital, Danmark
   

• ​​Helse Sør-Øst

• Gilead Nordic Medical Grants
• Norsk overvåkingssystem for antibiotikaresistens hos mikrober (NORM)
• Sykehuset i Vestfold​
  
• John C Martin Foundation 
  
• Gavi (The vaccine alliance)
  
• European Association for the Study of the liver (EASL)
  
• Norsk forskningsråd