Title Promoter Affiliations Abstract "Molecular epidemiology of HIV and hepaciviruses" "Philippe Lemey" "Laboratory of Clinical and Epidemiological Virology (Rega Institute)" "Combating pathogen spread and its associated disease burden is a tremendous challenge requiring sustained research effort and decided public health measures. The availability of genomic data provides a major asset in characterizing viral emergence and the interplay between viral evolution and host ecological dynamics, including the determination of the key factors for interspecies transmissions and successful epidemic spread in the human population.In this project, we will investigate the evolutionary origins and epidemic emergence of two important human viruses: hepatitis C virus (HCV) and human immunodeficiency virus (HIV). While the zoonotic origins of HIV-1 have been clearly established, an animal population that might have transmitted HCV to humans has not been identified yet. Inspired by recent findings of divergent hepaciviruses in rodents, we will perform a comprehensive investigation of hepacivirus diversity in various African rodent species to provide insights into the evolutionary origins of HCV. To this purpose, we will generate sequence data from a large set of African rodent samples and perform in-depth phylogenetic and phylogeographic analyses. While phylogenetic studies have contributed to our understanding of early epidemic onset in the Democratic Republic of Congo (DRC), historical estimates remain inherently uncertain. Motivated by the demonstrated possibility to inform such analyses with HIV-1 sequences recovered from archival specimens that date back decades ago (and thus are equivalent to molecular fossils), we propose as a second part of this project to scrutinize a unique, comprehensive library of archival samples from the putative heart of the pandemic in Central Africa we have collected over the years. We will complement these efforts by extending state-of-the-art phylogenetic reconstruction methodology to further refine time-estimates for the origin of HIV-1 group M, and to reconstruct the dynamics in viral population size and spatial expansion over time. The project will integrate experimental and computational work, and for both objectives, we build on existing collaborations with world leaders in the respective fields." "Genetic diversity and molecular epidemiology of hantaviruses" "Piet Maes, Marc Van Ranst" "Laboratory of Clinical and Epidemiological Virology (Rega Institute)" "Hantaviruses are zoonotic pathogens responsible for hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS) after human transmission. Pathogenic hantaviruses primarily have rodents as their reservoir, with humans acting as an accidental dead-end host. The actual hantavirus host range appears to be much broader with hantaviruses detected in shrews, moles, bats, reptiles, and fish. In Western, Northern, and Central Europe, Puumala virus, that has the bank vole as their natural host, is the most prominent causative agent of HFRS. At the moment, no effective antivirals and WHO-prequalified vaccines are available, making identification of local outbreaks and prevention of subsequent infections the most effective response. As zoonotic agents, hantaviruses are strongly influenced by changes in ecological and environmental factors and much effort is invested in identifying these drivers, what could aid in estimating the effective infection risk. Characterization of short-term evolution can help uncover recent virus dynamics and their influencing factors while investigating long-term evolution could provide insights into the evolutionary mechanisms shaping the relationship between hantaviruses and their hosts. This thesis attempts to characterize PUUV dynamics and factors influencing the human infection risk in Belgium. In addition, the genetic diversity and evolutionary history of non-rodent hantaviruses in Belgium are described." "Molecular epidemiology and antimicrobial resistance mechanism of Campylobacter species among children under the age of five with diarrhoea, domestic animals and environmental sources in Amhara National Regional State, Ethiopia" "Marie Joossens" "Department of Veterinary and Biosciences, Department of Biochemistry and microbiology, Department of Veterinary Public Health and Food Safety, Bahir Dar University" "This study is aimed at determining the molecular epidemiology and mechanism of antimicrobial resistance in Campylobacter. Specimens from various sources will be analysed using molecular tools.The nutritional status of children will be measured. The study will contribute to the understanding of the epidemiology and transmission dynamics of Campylobacter and help reduce the burden of diarrhoea and malnutrition in children." "An integrated approach of genetic epidemiology and molecular genetics in the study of Alzheimer dementia and related phenotypes." "Christine Van Broeckhoven" "VIB CMN - Neurodegenerative Brain Diseases Group" "This project aims to contribute to a better understanding of the genetic etiology of complex forms of Alzheimer dementia by means of genetic-epidemiological and molecular genetic techniques. This will help in identifying molecular mechanisms that can serve as targets for early detection, prevention and treatment of this common and incurable disease. High-throughput association studies (both genome-wide and focused on biological pathways) and intermediary or endophenotypes will be performed in a well-characterized study population with sufficient statistical power. Translation of findings to prodromal stages of AD will point out which factors are already of relevance early in the pathological cascade. These factors might find use as early predictors. Pathway analysis will identify subgroups with an increased epidemiological risk profile. In addition, we will assess if these prognostic markers affect easily measurable quantitative traits, e.g. in an integrated study of genome wide genotype data and differential protein expression in a proteomics study. If a correlation can be demonstrated, this trait can be used as a biomarker specific to the disease process. In addition we aim to identify genetic factors that modify onset age, to find novel targets for treatment, to delay or prevent the pathological cascade." "Unraveling the molecular basis and genetic epidemiology of Charcot-Marie-Tooth neurpathies: contribution from Northeast Brazil." "Albena Jordanova" "VIB CMN - Molecular Neurogenomics" "In this study we aim to deliver a better understanding of the molecular basis and genetic epidemiology of CMT by finding novel causative genes and performing genotype-phenotype correlations, as they offer partical advantages form a biological and translational perspective. Our unique entry point is an ethnically diverse collection of families and sporadic patients from Northeast Brazil, a geographic area not representied on the epidemiological map of Charcot-Marie-Tooth." "Streptococcus pneumoniae in conjugate vaccine period: epidemiology and molecular characterization" "Laboratory of Clinical Microbiology, Laboratory of Clinical and Epidemiological Virology (Rega Institute)" "Vaccination of young children with pneumococcal conjugate vaccines is an importanttool to decrease the burden of pneumococcal disease.In the first chapter we investigated the evolution of invasive pneumococcal diseasein Belgium during the sequential use of different pneumococcal conjugate vaccines(2007-2018) with a focus on the period aft er the switch from PCV13 to PCV10 (2016-2018). During the study period, a stable IPD surveillance and stable high vaccinati oncoverage in Belgium was observed. Aft er a signifi cant decrease during the PCV13period, paediatric invasive pneumococcal disease incidence increased again duringthe PCV10 period. This observation resulted mainly from a fast resurgence of PCV13-only serotype invasive pneumococcal disease, which was mainly related to serotype19A, which became predominant in paediatric IPD. These observations together withrecent reports regarding the long-term impact of PCV10 on IPD suggest that thecross-protecti on of PCV10 against serotype 19A based on immunogenicity studiesand short-term studies, may not be as effectivee as PCV13 in preventing serotype 19AIPD. The increase in IPD incidence due to an increase in serotype 19A IPD, a serotypeincluded in PCV13 but not in PCV10, resulted in the decision to switch back fromPCV10 to PCV13 in the Belgian childhood vaccinati on programmes in 2019.In the second chapter we investigated the carriage of S. pneumoniae on the nasopharynxof children attending day-care centres during and after the switch from PCV13to PCV10 (2016-2018). While the carriage rate of pneumococci in the nasopharynxof children attending day-care centres in Belgium was high and stable, a significantchange in the proportion of PCV13 only serotypes was detected during the 3-yearfollow-up period. The increase in the proportion of serotype 19A in carriage was concurrentwith the increase seen in IPD in children with the same age during the periodpost PCV13 to PCV10 switch. These concurrent evolutions of serotype 19A in IPDand carriage in the same age group are probably a result of the high invasive diseasepotenti al of serotype 19A. In contrast to the increase of serotype 19A aft er the vaccineswitch, the rate of the other two PCV13-non-PCV10 serotypes, i.e. serotype 3 and 6A,remained low and stable both in carriage and IPD in children.Based on the parallel design of the IPD surveillance and the carriage study, weexplored the relation between S. pneumoniae strains that were carried by youngchildren attending day care centres and S. pneumoniae strains that caused IPD inchildren during and aft er the PCV13-to-PCV10 switch (2015-2018). Different serotypesdominated in carriage (23B, 23A, 11A, 15B) versus IPD (12F, 19A, 10A, 33F). Weobserved that the most invasive serotypes (12F, 1, 3, 24A/B/F, 33F, 19A, and 9N) werenot frequently carried. On the other hand, the predominant serotypes in carriage onlyinfrequently caused IPD, which is mainly in accordance with observations from other studies. Only some of the serotypes with high invasive disease potenti al (serotype 1,3, 19A) in Belgium are included in PCV10 and/or PCV13, which underscores the needand the potential of new higher valent PCVs.Both in IPD and carriage an increase in serotype 19A post PCV13 to PCV10 switchwas observed. We developed a whole-genome sequencing protocol to characterizepneumococci. The sequencing of a total of 166 serotype 19A IPD isolates fromchildren and older adults, and carriage isolates from healthy children from thesame period after the vaccine switch (2017-2018) revealed presence of 24 diff erentsequence types. Two sequence types, ST416 and ST994, accounted together forthe majority of serotype 19A strains both in IPD in children and adults and carriage.These STs differed from the predominant 19A IPD STs in children after introductionof the 7-valent pneumococcal vaccine in Belgium (ST193 and ST276), which indicatesthat prediction of emerging strains cannot be completely based on historical strainsin childhood IPD. While both aft er PCV7 and PCV10 introducti on a rise in serotype19A was detected, the impact on the micro epidemiology of serotype 19A is differentthrough the emergence of diff erent clones. Despite their susceptible antibiotic profile,ST416 and ST994 clones expanded both in carriage and IPD during PCV10 use. Furtherexploration of the characteristics of these strains and comparison of the Belgian strainswith serotype 19A strains from both PCV13 and PCV10 using countries is needed tobetter understand the emergence of the predominant clones during the use of PCV10in Belgium.Our study delivers important informati on for policy makers and underscores theimportance of good surveillance systems to closely follow-up the potential impactof changes in vaccination strategy. Deep characterization of pneumococci can helpto better understand changes in epidemiology. A better understanding of the emergenceof specific pneumococcal clones is needed to be able to better forecast serotypereplacement associated with changes in vaccination programmes and its impacton pneumococcal disease and carriage. " "Joint project to strenghten research skills on molecular epidemiology and to uncover malaria transmission features relevant for its control in the Peruvian Amazon." "Jean-Pierre Van geertruyden" "Epidemiology and social medicine (ESOC)" "The present project seeks to fulfil the academic capabilities of UNAP by improving quality of research and education. The project relies in the formation of a triangular structure of academic and educational collaboration between the UNAP (public university, academically weak but with high potential as key player in the development of Amazon population), UPCH (well-stablished university will lead UNAP on the project) and UA (supporting the capacity building). The VLIR Sl project will strengthen the academic and operational capacities on molecular epidemiology through active coaching and training in epidemiology, biostatistics and population genetics. From the start of the project UA will provide support to the Peruvian partners on population genetics analysis for which a computer cluster and the respective training will be provided in Peru." "Real-time approach to the molecular epidemiology and evolutionary investigation and surveillance of acute viral epidemics." "Philippe Lemey" "Laboratory of Clinical and Epidemiological Virology (Rega Institute)" "Genomic analyses have revealed critical insights into the evolution and transmission of infectious agents in recent viral outbreaks, and offered tantalizing examples of the potential value of this approach to future outbreak control efforts. However, the scale and impact of new DNA technologies in these outbreaks has largely been stunted, due to the lack of a systematic and concerted effort. This proposal aims to overcome these challenges by establishing a statistically rigorous analysis framework and information-sharing platform that allows efficiently incorporating viral genomic data as an epidemic unfolds.For this purpose, we will build on the time-measured phylogenetic methodology in the BEAST framework and adopt state-of-the-art statistical techniques to accommodate a continuous process of data acquisition and inference. We will complement this with advanced Bayesian inference procedures that can be coupled to parallel computation to deal with the computational burden associated with large data sets. Finally we will develop a web-based visualization platform where the outputs of the statistical analyses can be interrogated for epidemiological insights within days of sampling. The data-sharing policy of our system will prioritize public health efforts without jeopardizing scientific publication.We anticipate that this research will prepare us for the next outbreak and ensure that viral genome sequencing is positioned to have full impact on the public health response." "Genetic Characterization and molecular epidemiology of equine herpes virus 1 in working equids in Ethiopia" "Hans Nauwynck" "Department of Translational Physiology, Infectiology and Public Health" "Equine herpesvirus 1 (EHV1) causes severe diseases in equines worelwide. Hovever, in Ethiopia there is no EHV1 vaccination program. A better understanding of the molecular epidemiology and diversity of EHV1 will provide insights for the design of appropriate control strategies. As a result, the impact of EHV1 on equine losses and subsequently on the poverty of farmers in Ethipoia will be reduced." "Development and implementation of a Chlamydophila psittaci molecular diagnostic platform to study the epidemiology of the infection and for tracing zoonotic transmission from birds to man" "Daisy Vanrompay" "Department of Molecular biotechnology" "Psittacosis still presents an epidemiologic and diagnostic challenge. Both prevalence and diagnosis are the subject of this study. We aim to compare different diagnostic technics and evaluate the influence of a number of factors on the transfer from bird to main."