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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
1

Utvecklingen av nya vacciner mot ebolafeber : Erfarenheter efter senaste utbrottet i Kongo 2018 / The development of new vaccines against ebola fever : Experiences after the recent outbreak in Congo 2018

Nilsson, Marina January 2020 (has links)
Introduction: Since the first outbreaks of Ebola virus disease 1976 in the Democratic Republic of the Congo (DRC) and Sudan there has been recurrent epidemics. The biggest outbreak so far hit West Africa between 2013-2016 when at least 28 600 people were estimated to have been infected and approximately 11 300 died in the most severely affected countries Guinea, Sierra Leone and Liberia. Ebola hemorrhagic fever (EHF) or Ebola virus disease (EVD) is caused by a virus that together with the Marburg virus belongs to the Filovirus family. The Ebola virus can cause hemorrhagic bleeding, has a rapid disease progression rate and a high mortality (25-90%). The symptoms are initially headache, fever, sore throat and muscle pain but during the latter part of the disease the characteristic bleedings from all bodily orifices occurs. Many internal organs do damage and survivors often have persistent sequels and long convalescense. EVD is a zoonosis and might infect antelopes, monkeys, porcupines among others. The natural reservoir is believed to be different species of bats. In august 2018, another outbreak of Ebola was reported in DRC. This was the tenth time the disease hit the country. However, for the first time there was candidate vaccine in clinical trial that could be used during an emergency. Experts within the WHO recommended that vaccination was initiated using Merck`s Ebolavaccine rVSV-∆G-ZEBOV-GP that was ready for a phase III clinical trial. This vaccine had already been used during the West African outbreak and had been known to provide a good safety profile as well as immunogenicity. The second vaccine to be used was a two-dose heterologous prime-boost vaccine regimen called Ad26.ZEBOV/MVA-BN-Filo which was marketed by Johnson&Johnson. Ad26.ZEBOV was given as a first dose to prime the immune system and then MVA-BN-Filo was administered as a second dose approximately 8 weeks later as a booster. This vaccine regimen had also been showing promising results in phase I and II clinical trials. Objective: This degree project was made in attempt to answer the issue: How effective and safe are the new Ebola vaccines against EVD? Methods: To answer this question, a literature study was conducted. The outbreak in DRC was ongoing by the time of this degree project and there were no phase III trials conducted for the Ad26.ZEBOV/MVA-BN-Filo vaccine regimen. A lot of information was therefore retrieved from WHO, Doctors without borders, and so on. Merck`s vaccine had been prequalified and received the generic name Ervebo in the fall of 2018. Randomised clinical trials (RCT) and clinical trials regarding Ervebo was downloaded from the internet using the search engine PubMed that`s accessing different databases. Results: Both Ervebo and the 2-dose vaccine regimen Ad26.ZEBOV/MVA-BN-Filo initiated an immune response against ebolavirus that was almost 100%. The most frequent solicited local and systemic adverse events were injection site pain and headache, myalgia and fever. All adverse events were reported to be mild and resolved in a short period of time. No severe adverse events were reported. Discussion: The biggest challenge in the future will concern how to initiate vaccination strategies in countries with a lack of financial resources and infrastructure as well as ongoing armed conflicts (mainly DRC). Conclusion: The new vaccines against Ebola virus infection are all effective with a good safety profile. / Bakgrund: Sedan de första utbrotten av ebolafeber 1976 i Demokratiska republiken Kongo (DRK) och Sudan har epidemier blossat upp med jämna mellanrum. Det hittills största utbrottet drabbade Västafrika 2013-2016 då minst 28 600 beräknades ha smittats och minst 11 300 avled i de hårdast drabbade länderna Guinea, Sierra Leone och Liberia. Ebolafeber, eller ebola hemorragisk feber, orsakas av ett virus som tillsammans med Marburgviruset hör till familjen Filovirus. Ebolaviruset kan orsaka hemorragiska blödningar, har snabbt sjukdomsförlopp och hög dödlighet (25-90%). Symptomen är inledningsvis influensaliknande men under den senare delen av sjukdomsförloppet förekommer de karaktäristiska blödningarna från alla kroppsöppningar. Många inre organ tar skada och överlevare har ofta bestående men och lång konvalescens. Ebolafeber är en zoonos och kan drabba antiloper, olika sorters apor m fl. Den naturliga reservoaren tros vara olika arter av fladdermöss. I augusti 2018 rapporterades om ännu ett utbrott av ebolafeber i DRK, det 10:e i ordningen. En avgörande skillnad vid detta utbrott var att det nu fanns kandidatvaccin i kliniska studier att tillgå. En expertgrupp inom WHO rekommenderade att vaccination inledddes med rVSV-∆G-ZEBOV, ett ebolavaccin tillverkat av Merck redo för kliniska studier fas III. Detta vaccin hade använts redan under utbrottet i Västafrika och visat goda resultat vad gällde immunogenicitet och säkerhet. Det andra vaccinet att sättas in var Ad26.ZEBOV/MVA-BN-Filo, tillhandahållet av Johnson&Johnson. Detta bestod av två olika doser som gavs med ca 8 veckors mellanrum, ofta kallat ”prime/boost”-vaccin. Även för Ad26.ZEBOV/MVA-BN-Filo fanns dokumenterade positiva resultat. Syfte: Detta examensarbetet gjordes med syftet att svara på frågeställningen: Hur effektiva och säkra är de nya vaccinen mot ebolafeber? Metod: För att svara på frågan gjordes en litteraturstudie. När detta examensarbete författades pågick fortfarande utbrottet i DRK och fas III studierna för Ad26.ZEBOV/MVA-BN-Filo var inte avslutade. Mycket information fick hämtas från olika hemsidor, bl a WHO och Läkare utan gränser. Mercks vaccin prekvalificerades hösten 2019 och gavs handelsnamnet Ervebo. För detta vaccin fanns fler RCT-studier tillgängliga, vilka uteslutande valdes m h a sökmotorn PubMed som är länkad till olika databaser. Resultat: Både singeldosvaccinet Ervebo och dubbeldosvaccinen Ad26.ZEBOV/MVA-BN-Filo konstaterades ge ett nästan 100%-igt immunsvar mot ebolavirus. I den mån biverkningar förekom var de milda och övergående. Den mest rapporterade lokala biverkningen var ömhet vid injektionsstället och de vanligaste systemiska biverkningarna var huvudvärk, myalgi och feber. Diskussion: Den största utmaningen i framtiden blir att inleda vaccinationsprogram i länder med bristande finansiella resurser och infrastruktur samt pågående väpnade konflikter (främst DRK). Slutsatsen blev att de nya vaccinen mot ebolafeber är effektiva och säkra vid behandling mot ebolavirusinfektion.

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