Biology subjects

Gilbert, M.

Publications and source records attributed to Gilbert, M..

5 recordsLinked to original sources

bioRxiv2018

Robustness of local control strategies under modelling uncertainties: the 2004 avian infuenza H5N1 outbreak in Thailand

The Highly Pathogenic Avian Influenza (HPAI) subtype H5N1 virus persists in many countries and has been circulating in poultry, wild birds. In addition, the virus has emerged in other species and frequent zoonotic spillover events indicate that there remains a significant risk to human health. It is crucial to understand the dynamics of the disease in the poultry industry to develop a more comprehensive knowledge of the risks of transmission and to establish a better distribution of resources when implementing control. In this paper, we develop a set of mathematical models that simulate the spread of HPAI H5N1 in the poultry industry in Thailand, utilising data from the 2004 epidemic. The model that incorporates the intensity of duck farming when assessing transmision risk provides the best fit to the spatiotemporal characteristics of the observed outbreak, implying that intensive duck farming drives transmission of HPAI in Thailand. We also extend our models using a sequential model fitting approach to explore the ability of the models to be used in \"real time\" during novel disease outbreaks. We conclude that, whilst predictions of epidemic size are estimated poorly in the early stages of disease outbreaks, the model accurately predicts the preferred control policy that should be deployed to minimise the impact of the disease.

epidemiology↗

bioRxiv2018

Genetics behind the biosynthesis of nonulosonic acid containing lipooligosaccharides in Campylobacter coli

Campylobacter jejuni and Campylobacter coli are the most common cause of bacterial gastroenteritis in the world. Ganglioside mimicry by C. jejuni lipooligosaccharide (LOS) is the triggering factor of Guillain-Barre syndrome (GBS), an acute polyneuropathy. Sialyltransferases from the glycosyltransferase (GT) family 42 are essential for the expression of ganglioside mimics in C. jejuni. Recently, two novel GT-42 genes, cstIV and cstV, have been identified in C. coli. Despite being present in [~]11% of currently available C. coli genomes, the biological role of cstIV and cstV is unknown. In the present study, mutation studies in two strains expressing either cstIV or cstV were performed and mass spectrometry was used to investigate differences in the chemical composition of LOS. Attempts were made to identify donor and acceptor molecules using in vitro activity tests with recombinant GT-42 enzymes. Here, we show that CstIV and CstV are involved in C. coli LOS biosynthesis. In particular, cstV is associated with LOS sialylation, while cstIV is linked to the addition of a diacetylated nonulosonic acid residue.\n\nIMPORTANCEDespite being a major foodborne pathogen, Campylobacter coli glycobiology has been largely neglected. The genetic makeup of the C. coli lipooligosaccharide biosynthesis locus was largely unknown until recently. C. coli harbour a large set of genes associated to lipooligosaccharide biosynthesis, including several putative glycosyltransferases involved in the synthesis of sialylated lipooligosaccharide in Campylobacter jejuni. In the present study, C. coli was found to express lipooligosaccharide structures containing sialic acid and other nonulosonate acids. These findings have a strong impact in understanding C. coli ecology, host-pathogen interaction, and pathogenesis.

microbiology↗

bioRxiv2017

The impact of surveillance and control on highly pathogenic avian influenza outbreaks in poultry in Dhaka division, Bangladesh

In Bangladesh, the poultry industry is an economically and socially important sector, but it is persistently threatened by the effects of H5N1 highly pathogenic avian influenza. Thus, identifying the optimal control policy in response to an emerging disease outbreak is a key challenge for policy-makers. To inform this aim, a common approach is to carry out simulation studies comparing plausible strategies, while accounting for known capacity restrictions. In this study we perform simulations of a previously developed H5N1 influenza transmission model framework, fitted to two separate historical outbreaks, to assess specific control objectives related to the burden or duration of H5N1 outbreaks among poultry farms in the Dhaka division of Bangladesh. In particular, we explore the optimal implementation of ring culling, ring vaccination and active surveillance measures when presuming disease transmission predominately occurs from premises-to-premises, versus a setting requiring the inclusion of external factors. Additionally, we determine the sensitivity of the management actions under consideration to differing levels of capacity constraints and outbreaks with disparate transmission dynamics. While we find that reactive culling and vaccination policies should pay close attention to these factors to ensure intervention targeting is optimised, across multiple settings the top performing control action amongst those under consideration were targeted proactive surveillance schemes. Our findings may advise the type of control measure, plus its intensity, that could potentially be applied in the event of a developing outbreak of H5N1 amongst originally H5N1 virus-free commercially-reared poultry in the Dhaka division of Bangladesh.

epidemiology↗

bioRxiv2017

Changing geographic patterns and risk factors for avian influenza A(H7N9) infection in China

The 5th epidemic wave in 2016-2017 of avian influenza A(H7N9) virus in China caused more human cases than any previous waves but the factors that may explain the recent range expansion and surge in incidence remain unknown. We investigated the effect of anthropogenic, poultry and wetland information and of market closures on all epidemic waves (1-5). Poultry predictor variables recently became much more important than before, supporting the assumption of much wider H7N9 transmission in the chicken reservoir, that could be linked to increases in pathogenicity. We show that the future range expansion of H7N9 to northern China may translate into a higher risk of coinciding peaks with those of seasonal influenza, leading to a higher risk of reassortments. Live-poultry market closures are showed to be effective in reducing the local incidence rates of H7N9 human cases, but should be paired with other prevention and control measures to prevent transmission.

epidemiology↗

bioRxiv2017

Preexisting antibodies can protect against congenital cytomegalovirus infection in monkeys

Human cytomegalovirus (HCMV) is the most common congenital infection and a known cause of microcephaly, sensorineural hearing loss, and cognitive impairment among newborns worldwide. Natural maternal HCMV immunity reduces the incidence of congenital infection, but does not prevent the disease altogether. We employed a nonhuman primate model of congenital CMV infection to investigate the ability of preexisting antibodies to protect against placental CMV transmission. Pregnant, CD4+ T cell-depleted, rhesus CMV (RhCMV)-seronegative rhesus monkeys were treated with either standardly-produced hyperimmune globulin (HIG) from RhCMV-seropositive macaques or dose-optimized, potently RhCMV-neutralizing HIG prior to intravenous challenge with an RhCMV swarm. HIG passive infusion provided complete protection against fetal loss in both groups, and the potently-neutralizing HIG additionally inhibited placental transmission of RhCMV. Our findings suggest that antibody alone at the time of primary infection can prevent congenital CMV and therefore could be a primary target of vaccines to eliminate this neonatal infection.

immunology↗