Dissertations / Theses on the topic 'Lassa fever'
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Wilkinson, Ann. "The process and practice of diagnosis : innovations in diagnostics for Lassa fever in Sierra Leone." Thesis, University of Sussex, 2013. http://sro.sussex.ac.uk/id/eprint/47209/.
Full textKrasilnikova, Lydia A. "Metagenomic investigation of co-infections of Ebola virus disease and Lassa fever patients." Thesis, Massachusetts Institute of Technology, 2016. http://hdl.handle.net/1721.1/106113.
Full textCataloged from PDF version of thesis.
Includes bibliographical references (page 37).
Sequencing followed by metagenomic analysis is an extremely promising method for broad, unbiased disease profiling of patients for disease surveillance and diagnosis. Here, we use two popular metagenomics tools in union, k-mer-based Kraken with reads and BLAST- and LCAbased MEGAN with assembled contiguous sequence. We analyze sequence from 463 febrile and afebrile patients from Sierra Leone before and during the 2014 Ebola virus outbreak. We find that co-infection with malaria is correlated with increased survival of Ebola virus patients, from 18% survival rate to 53%. We also explore the utility of and emphasize the need for both positive and negative controls to distinguish and remove noise and contaminants from real signal, especially to keep up with increasing sensitivity in sequencing.
by Lydia A. Krasilnikova.
M. Eng. in Computer Science and Molecular Biology
Baillet, Nicolas. "Pathologie comparée de la fièvre de Lassa chez le singe cynomolgus : mécanismes pathogéniques précoces, réponses immunitaires et marqueurs d’infection." Thesis, Lyon, 2018. http://www.theses.fr/2018LYSE1307.
Full textLassa virus causes a hemorrhagic fever endemic in West Africa and represents a threat for civilians. The pathogenesis and the immune responses associated with the disease are poorly understood. We followed pathological, virological and immunological parameters associated with fatal and non-fatal Lassa virus infection in the cynomolgus monkey. The clinical picture was characterized by depression, anorexia, weight loss and asthenia in survivors whereas the same symptoms were supported by fever, respiratory difficulties and epistaxis in animals infected with the lethal dose. Only fatalities have shown coagulation parameters dysfunction, rhabdomyolysis and an increase of renal function markers. We observed a different viral tropism in a function of the disease severity, with viral dissemination in organs that was more important and faster in fatalities, the appearance of numerous infectious particles number and more severe pathologic changes. Early and robust innate and adaptive immune response has been associated with the control of infection and recovery whereas fatal infections were characterized by a sepsis like inflammatory response, defective immune response as well as uncontrolled viral replication. This study sheds light on the pathogenesis of Lassa fever and reveals infection markers predictive of the disease outcome
Cedergren, Linda. "Expression of recombinant protein including an His-tag to facilitate purification for diagnosis of CCHF and Lassa Viruses." Thesis, Uppsala University, Department of Medical Biochemistry and Microbiology, 2006. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-7064.
Full textAbstract
Crimean-Congo Hemorrhagic Fever virus (CCHF) and Lassa virus are giving sources illness to humans. In addition to zoonotic transmission, CCHF and Lassa virus can spread from person to person. After a short incubation period, CCHF and Lassa virus infections are characterized by a sudden onset of high fever, chills, headache and cough just like flu. Even some people are vomiting and have diarrhoea. After a few days of illness hemorrhagic manifestations occur. Treatment options for CCHF and Lassa viruses are limited, and there is no vaccine available for use in humans. The purpose of the present study was to produce recombinant nucleocapsid protein of Lassavirus and CCHF virus including an aminoterminal His-tag by a Semliki Forest Virus Replicon (pSFV 4.2). The recombinant proteins are planned to be used in future development of diagnostic methods.
Duvignaud, Alexandre. "Aspects cliniques, biologiques et pronostiques de la fièvre de Lassa en contexte endémo-épidémique en Afrique de l’Ouest : exemple du Nigeria." Thesis, Bordeaux, 2020. http://www.theses.fr/2020BORD0254.
Full textLassa fever, an endemic disease with seasonal epidemic recrudescence, is considered to be responsible for 300 000 cases and 5000 death each year throughout Western Africa. As such, it has been listed as a priority for research. Over the past few years, Nigeria reported the highest and ever increasing number of cases, now exceeding a thousand per year. However, fifty years after the discovery of the disease, our knowledge is still limited and clinical research capacities remained poorly developed. The efficacy of the only available treatment, ribavirin, is still to be assessed. Hence, there is a need for up to date and reliable data on the disease course, management, mortality and prognostic factors. It is also of paramount importance that the patients suffering from Lassa fever could gain access to an optimised standard of care. Lastly, clinical research capacities need to be developed urgently in endemic areas.In this thesis, we review the knowledge gathered on Lassa fever from its discovery in 1969 till date. Then, we explain the reasons that led us to set up a response and research program on Lassa fever, as well as our approach to reinforce the standard of care and build a clinical research platform in collaboration with one of the main Lassa treatment centres in Nigeria. Next, we present the first results of the LASCOPE cohort study which represent the cornerstone of our program.From April 2018 to March 2020, 534 patients with RT-PCR proven Lassa fever were followed-up of whom 77 died (14.4%). 510 participants were enrolled in the cohort: 258 men and 252 women, 84 being children. The median delay between the symptoms onset and admission was 8 days (IQR 7-13). On admission, 37.8% had a Lassa RT-PCR Ct value <30. From admission to end of follow-up, 120 (26.5%) had a NEWS2 ≥7, 67(13.5%) had a KDIGO ≥2, and 41 (8.0%) underwent dialysis. All of them received ribavirin therapy with a median duration of 10 days (IQR 9-13). 62 (12.2%) died (57 [13.4%] adults, 5 [6.0%] children. The median delay between admission and death was 3 days (IQR 1-6). The following characteristics on admission were independently associated to mortality: age ≥ 45 years (adjusted Odds Ratio [aOR] 16.30 [95%CI 5.31-50.30]), NEWS2 ≥7 (aOR 4.79 [95%CI 1.75-13.10]), KDIGO ≥2 (aOR 7.52 [95%CI 2.66-21.20]), ALAT ≥ 3 times the upper limit of normal range (aOR 4.96 [95%CI 1.69- 14.60]), a Lassa RT-PCR Ct value <30 (aOR 4.65 [95%CI 1.50-14.50]). Those results will be helpful for the conception of future therapeutic clinical trials as well as for updating existing management guidelines. The framework of this cohort also gave us the opportunity to describe an unusual presentation of the disease, namely delayed paraparesis. This original observation add to the evolving knowledge regarding the spectrum of Lassa fever-related neurological manifestations.Two complementary studies are nested in the LASCOPE cohort, concerning the pharmacokinetics of ribavirin, as it is used for the treatment of Lassa fever, as well as the pathophysiology of cardiovascular dysfunction that can occur during Lassa fever. Inclusions in these nested studies is still ongoing.Finally, an upcoming phase II clinical trial evaluating the pharmacokinetics, security and tolerability of a novel antiviral drug, favipiravir, for the treatment of Lassa fever is currently being prepared in two Nigerian sites, including the one we are collaborating with
Qi, Xiaoxuan. "Structural and functional studies of novel mechanisms of Lassa fever virus nucleoprotein in immune suppression, viral RNA transcription and replication." Thesis, University of St Andrews, 2012. http://hdl.handle.net/10023/3601.
Full textPort, Julia Rebecca [Verfasser], Lars [Akademischer Betreuer] Redecke, and Tamás [Akademischer Betreuer] Laskay. "Implications of T-lymphocyte homing in Lassa fever pathogenesis and transmission / Julia Rebecca Port ; Akademische Betreuer: Lars Redecke, Tamás Laskay." Lübeck : Zentrale Hochschulbibliothek Lübeck, 2021. http://d-nb.info/1228017913/34.
Full textWallat, Gregor D. "Structure determination of the major outer membrane protein from Campylobacter jejuni, &, Structural and functional studies of the endonuclease from Lassa virus." Thesis, University of St Andrews, 2015. http://hdl.handle.net/10023/8112.
Full textOffor, Joy. "Lassa fever epidemic outbreak causing maternal mortality on pregnant women : A statistical and systematic review on prevalence and occurrence of maternal mortality in Nigeria." Thesis, Södertörns högskola, Institutionen för naturvetenskap, miljö och teknik, 2020. http://urn.kb.se/resolve?urn=urn:nbn:se:sh:diva-42026.
Full textSchaeffer, Justine. "Étude in vitro et ex vivo de la réponse des cellules dendritiques à l’infection par le virus Lassa." Thesis, Lyon, 2018. http://www.theses.fr/2018LYSE1249/document.
Full textLassa virus (LASV) is responsible for a viral haemorrhagic fever in humans and the death of 3,000 to 5,000 people every year. There is currently no vaccine or treatmentavailable against LASV, and its pathogenesis is not completely understood yet. According to studies on humans and primates, type I interferon (IFN-I) and T cell responses appear to be critical for the host. We studied the response of dendritic cells (DC) to LASV, as DC are involved in both IFN-I production and T cell activation. We compared the response of primary human DC to LASV and Mopeia virus (MOPV), which is similar to LASV, but non-pathogenic.We focused on plasmacytoid DC (pDC), specialized in IFN-I production, and myeloid DC (mDC), specialized in antigen presentation. We showed that neither pDC nor mDC were productively infected by LASV and MOPV. pDC infected with MOPV produced large amounts of IFN-I, whereas pDC infected with LASV did not. mDC produced substantial amounts of IFN-I in response to both LASV and MOPV. However, only MOPV-infected mDC were able to activate T cells. More surprisingly, coculture with T cells completely inhibited the activation of LASV-infected mDC. These differences between LASV- and MOPV-infected mDC were mostly due to LASV nucleoprotein, which has major immunosuppressive properties, but the glycoprotein was also involved. Overall, these results showed differences in pDC and mDC response to MOPV and LASV. Therefore, both pDC and mDC may be important for the global response to LASV in vivo, and play a role in the outcome of Lassa fever
Russier, Marion. "Cellules NK et fièvres hémorragiques virales : étude de leur rôle dans la mise en place des réponses immunes et dans la pathogenèse lors de l'infection par les virus Lassa et Ebola." Phd thesis, Ecole normale supérieure de lyon - ENS LYON, 2013. http://tel.archives-ouvertes.fr/tel-00835079.
Full text"Characterization of arenaviral soluble glycoprotein biosynthesis and evaluation of Lassa virus-like particles as vaccine candidates for Lassa hemorrhagic fever." Tulane University, 2010.
Find full textacase@tulane.edu
"Untargeted Lcms Serum Metabolomics Of The Sierra Leonean Lassa Fever Patient And Metaanalysis Of The Virion Proteome." 2016.
Find full text"Knowledge, attitude, and practices of Lassa fever transmission and perceived risk increase likelihood of rodent control activities and reduction in homes." Tulane University, 2021.
Find full textMota, Tiago José Abreu. "Development of a Lassa/Rabies virus vaccine based on the rabies vector." Doctoral thesis, 2019. http://hdl.handle.net/1822/66881.
Full textLassa fever (LF), is a viral hemorrhagic fever caused by Lassa virus (LASV), for which neither an approved vaccine or effective treatment is available. LASV is an endemic virus in western Africa and a major health and economic burden, causing an estimate 100,000-300,000 infections yearly, with the number of reported infections increasing in the last years. This thesis describes the development of LASSARAB, a dual LF and rabies vaccine based on recombinant rabies vector. Rabies is another equally important disease in Africa that is estimated to cause thousands of deaths every year, despite vaccination being available. LASSARAB uses a codon optimized version of LASV’s glycoprotein (GPC) as its LASV immunogen. After confirming that LASSARAB expresses and incorporates GPC in the virions, LASSARAB’s potential as an LF vaccine was tested using several LASSARAB based vaccine candidates: inactivated LASSARAB formulated in PBS only; inactivated LASSARAB formulated with GLA-SE adjuvant (a TLR-4 agonist); live-LASSARAB; and live-LASSARAB-ΔG, a variant of LASSARAB that lacks the Rabies G gene. Inactivated LASSARAB formulations induced a significant GPC specific IgG response above background with LASSARAB+GLA-SE inducing higher IgG titers than LASSARAB alone as well as a lower IgG1/IgG2c ratio. Neither live- LASSARAB vector induced a significant LASV GPC immune response. In LASV challenge studies, in both guinea pig and mouse, inactivated LASSARAB+GLA-SE, significantly protected 80% of the animals against LF disease. Higher titers of anti-GPC IgGs were correlated with protection independently of LASV neutralizing titers. Instead, non-neutralizing LASV GPC-specific antibodies, through antibody-dependent cellular functions (ADCC and ADCP) appear to the main drivers of protection against LF as demonstrated by in vitro and in vivo studies. Overall, these findings demonstrate an effective inactivated LF and rabies vaccine and suggest a novel correlate of protection for LF. Currently, further LASSARAB immunogenicity studies using NHPs are underway determine its eligibility for clinical phase 1 trials.
A febre de Lassa (LF), é uma febre hemorrágica viral causada pelo vírus Lassa (LASV), para a qual não existe nem vacina ou tratamento aprovado. O LASV é um vírus presente na África ocidental que incute um pesado encargo na saúde pública regional, e estima-se que causa 100,000 a 300,000 infeções por ano. Esta tese é sobre o desenvolvimento de LASSARAB, uma potencial vacina contra a LF e Raiva baseada num vetor do vírus da Raiva recombinante. A Raiva, é outra doença igualmente importante em África que causa milhares de mortes todos anos apesar de haver vacina disponível. LASSARAB usa uma versão codon-optimized da glicoproteína de LASV (GPC) como o imunogénio de base contra LASV. Após confirmar que LASSARAB expressa e incorpora o LASV GPC nas partículas virais, o potencial de LASSARAB foi testado através de vários candidatos incluindo: LASSARAB inativado formulado em PBS apenas; LASSARAB inativado formulado com o adjuvante GLA-SE (um agonista TLR4); LASSARAB vivo; e LASSARAB-ΔG vivo, uma variante de LASSARAB que não expressa o gene da glicoproteína de raiva. Ambos os candidatos LASSARAB inativados induziram uma elevada resposta imune contra GPC, com LASSARAB+GLA-SE induzindo níveis de IgGs contra GPC mais elevados assim como um ratio IgG1/IgG2c mais baixo. Em estudos de exposição com LASV em porquinhos da Índia e ratinhos, o LASSARAB+GLA-SE inativo foi capaz de proteger em 80% os animais contra LF. Níveis mais elevados de IgGs específicos para GPC, foram correlacionados com proteção independentemente dos níveis de anticorpos neutralizantes contra LASV. Pelo contrário, IgGs específicos contra GPC não neutralizantes, através de funções celulares dependentes de anticorpos (ADCC e ADCP) parecem ser os principais intervenientes na proteção contra LF. Em conjunto, estes resultados demonstram uma vacina inativada eficaz contra LF e Raiva e sugerem uma correlação de proteção contra LF, baseado na resposta de IgGs específicos contra GPC. Atualmente, estudos em primatas estão a decorrer para testar a imunogenicidade de LASSARAB neste modelo em preparação para clinical phase 1 trials.
Financial support for this PhD was provided by FCT (Fundação para Ciência e Tecnologia), by the fellowship PD/BD/105847/2014, awarded through the MD/PhD program of University of Minho.
Smit, Andre-Karl. "Genetic variation in two morphologically similar South African Mastomys species (Rodentia : Muridae)." Thesis, 2012. http://hdl.handle.net/10210/7157.
Full textTwo species of multimammate mouse, Mastomys coucha and M. natalensis are common, and widely distributed in southern Africa, occurring sympatrically in some areas, and allopatrically in others. The limits of their distribution are only provisional so far. As they share a high degree of morphological similarity, they are, as yet, impossible to identify with certainty in the field. Each species of multimammate mouse carries important diseases: with M. coucha being a carrier for the bacterium causing plague, and M. natalensis carrying the virus causing Lassa fever. In many areas, multimammate mice, being highly adaptable and ecological generalists, have become co-habitants with humans. This fact, coupled to the medical significance of both species, lends importance to being able to identify each species where it occurs, especially in areas where they occur sympatrically. Thus, a total of 40 specimens of M. natalensis were trapped from Richards Bay and La Lucia ridge in KwaZulu-Natal, and 43 specimens of M. coucha from Montgomery Park in Johannesburg and from the shores of the Vaal Dam in the Free State with the aim of comparing these two species via gel electrophoresis. These specimens were from allopatric populations from the centres of their provisional distributions. It was expected that there would be genetic differences between the two sibling species. Blood, liver, and muscle samples were taken, either in the field from dead specimens caught in snap-traps, or back in the laboratory from live-trapped specimens. Fifteen proteins or enzymes provided interpretable results at a total of 39 loci. Nineteen of these were polymorphic
"Development Of Rapid Diagnostic Tests For The Point-of-care Detection Of Lassa And Ebola Viral Hemorrhagic Fevero." 2015.
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