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Ernest A. Gould - One of the best experts on this subject based on the ideXlab platform.
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molecular basis of a protective neutralizing monoclonal antibody targeting envelope proteins of both tick borne encephalitis virus and Louping Ill virus
Journal of Virology, 2019Co-Authors: Xu Yang, Ernest A. Gould, George F. Gao, Ruchao Peng, Lianpan Dai, Po TienAbstract:Tick-borne encephalitis virus (TBEV) and Louping Ill virus (LIV) are members of the tick-borne flaviviruses (TBFVs) in the family Flaviviridae which cause encephalomeningitis and encephalitis in humans and other animals. Although vaccines against TBEV and LIV are available, infection rates are rising due to the low vaccination coverage. To date, no specific therapeutics have been licensed. Several neutralizing monoclonal antibodies (MAbs) show promising effectiveness in the control of TBFVs, but the underlying molecular mechanisms are yet to be characterized. Here, we determined the crystal structures of the LIV envelope (E) protein and report the comparative structural analysis of a TBFV broadly neutralizing murine MAb (MAb 4.2) in complex with either the LIV or TBEV E protein. The structures reveal that MAb 4.2 binds to the lateral ridge of domain III of the E protein (EDIII) of LIV or TBEV, an epitope also reported for other potently neutralizing MAbs against mosquito-borne flaviviruses (MBFVs), but adopts a unique binding orientation. Further structural analysis suggested that MAb 4.2 may neutralize flavivirus infection by preventing the structural rearrangement required for membrane fusion during virus entry. These findings extend our understanding of the vulnerability of TBFVs and other flaviviruses (including MBFVs) and provide an avenue for antibody-based TBFV antiviral development. IMPORTANCE Understanding the mechanism of antibody neutralization/protection against a virus is crucial for antiviral countermeasure development. Tick-borne encephalitis virus (TBEV) and Louping Ill virus (LIV) are tick-borne flaviviruses (TBFVs) in the family Flaviviridae. They cause encephalomeningitis and encephalitis in humans and other animals. Although vaccines for both viruses are available, infection rates are rising due to low vaccination coverage. In this study, we solved the crystal structures of the LIV envelope protein (E) and a broadly neutralizing/protective TBFV MAb, MAb 4.2, in complex with E from either TBEV or LIV. Key structural features shared by TBFV E proteins were analyzed. The structures of E-antibody complexes showed that MAb 4.2 targets the lateral ridge of both the TBEV and LIV E proteins, a vulnerable site in flaviviruses for other potent neutralizing MAbs. Thus, this site represents a promising target for TBFV antiviral development. Further, these structures provide important information for understanding TBFV antigenicity.
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detection of Louping Ill virus in clinical specimens from mammals and birds using taqman rt pcr
Journal of Virological Methods, 2006Co-Authors: L. Marriott, Ernest A. Gould, K. Willoughby, F Chianini, M P Dagleish, Sandra Scholes, A C Robinson, P F NettletonAbstract:The identification of Louping Ill virus (LIV) in clinical specimens has been routinely achieved by virus isolation using susceptible pig kidney cells and subsequent serological analysis. While this method is sensitive and detects infectious virus, it is relatively labour intensive and time-consuming. In view of the veterinary and potential medical importance of LIV, a rapid and precise detection method for routine use that employs the TaqMan reverse transcription polymerase chain reaction (RT-PCR) has been developed to detect LIV RNA extracted from field samples. The TaqMan assay was evaluated against virus isolation using 22 cell culture grown LIV isolates, which had previously been partially characterised by sequencing, and material from 63 suspect field cases. Histopathological and/or serological reports were available for 39 of the suspect cases, providing additional diagnostic information to evaluate the results obtained from the TaqMan RT-PCR assay. The TaqMan assay was as sensitive as the cell culture infectious virus assay currently used and had the advantage that it was able to detect LIV in clinical specimens from which infectious virus could not be isolated possibly due to the presence of high levels of LIV antibody.
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THE EPIDEMIOLOGY OF Louping-Ill, A TICK BORNE INFECTION OF RED GROUSE (LAGOPUS LAGOPUS SCOTICUS)
Parassitologia, 1997Co-Authors: Peter J Hudson, Ernest A. Gould, Hugh W. Reid, Linda D. Jones, K. Laurenson, Michael W. Gaunt, Rachel Norman, K. Macguire, David NewbornAbstract:The epidemiology of Louping-Ill in red grouse was studied in northern Britain concentrating on the possible role of other species and mechanisms of disease persistence. This tick borne viral disease caused heavy mortality in red grouse, particularly chicks. Louping-Ill induced mortality reduced the strength of the density dependence that generates the tendency of grouse populations to cycle and in some populations may cause population sinks. Four routes of transmission were examined and non-viraemic transmission of virus between ticks cofeeding on hares was considered significant. Field data supported the hypothesis that disease dynamics is influenced greatly by mountain hares, both as passive amplifiers and as hosts for the tick vector. Genetic variation in Louping-Ill within Britain was small.
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Transmission of Louping Ill virus between infected and uninfected ticks co‐feeding on mountain hares
Medical and veterinary entomology, 1997Co-Authors: Linda D. Jones, Peter J Hudson, Hugh W. Reid, Michael W. Gaunt, Rosie S. Hails, Karen Laurenson, Pauline Henbest, Ernest A. GouldAbstract:Most of the data on oral infection of ticks by Louping Ill virus have been obtained from experiments in which animals were infected by syringe inoculation with infectious material. Using infected ticks to mimic the natural situation, we have demonstrated that Louping Ill (LI) virus transmission can occur from infected to uninfected Ixodes ricinus feeding in close proximity on mountain hares (Lepus timidus). Under these conditions the hares developed either low or undetectable viraemias. Highest prevalence of LI virus infection was observed in recipient nymphs which had fed to repletion between days 3 and 7 post-attachment of virus-infected adults; following engorgement, 56% of nymphs acquired virus. These results demonstrate the efficient transmission of LI virus between co-feeding ticks on naive mountain hares. However, when ticks were allowed to co-feed on virus-immune hares a significant reduction in the frequency of infection was observed. Neither red deer (Cervus elaphus) nor New Zealand White rabbits supported transmission of LI virus. The significance of virus transmission between cofeeding ticks on LI virus epidemiology is discussed.
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persistence and transmission of tick borne viruses ixodes ricinus and Louping Ill virus in red grouse populations
Parasitology, 1995Co-Authors: Peter J Hudson, David Newborn, H W Reid, Ernest A. Gould, Linda D. Jones, Michael W. Gaunt, Rachel Norman, M.k. Laurenson, Roger G Bowers, Andrew P DobsonAbstract:The population dynamics of tick-borne disease agents and in particular the mechanisms which influence their persistence are examined with reference to the flavivirus that causes Louping-Ill in red grouse and sheep. Pockets of infection cause heavy mortality and the infection probably persists as a consequence of immigration of susceptible hosts. Seroprevalence is positively associated with temporal variations in vectors per host, although variation between areas is associated with the abundance of mountain hares. The presence of alternative tick hosts, particularly large mammals, provides additional hosts for increasing tick abundance. Grouse alone can not support the vectors and the pathogen but both can persist when a non-viraemic mammalian host supports the tick population and a sufficiently high number of nymphs bite grouse. These alternative hosts may also amplify virus through non-viraemic transmission by the process of co-feeding, although the relative significance of this has yet to be determined. Another possible route of infection is through the ingestion of vectors when feeding or preening. Trans-ovarial transmission is a potentially important mechanism for virus persistence but has not been recorded with Louping-Ill and Ixodes ricinus. The influence of non-viraemic hosts, both in the multiplication of vectors and the amplification of virus through non-viraemic transmission are considered significant for virus persistence.
Hugh W. Reid - One of the best experts on this subject based on the ideXlab platform.
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Ticks need not bite their red grouse hosts to infect them with Louping Ill virus.
Proceedings of the Royal Society of London. Series B: Biological Sciences, 2004Co-Authors: Lucy Gilbert, Hugh W. Reid, Linda D. Jones, M. Karen Laurenson, E. A. Gould, Peter J HudsonAbstract:For pathogens transmitted by biting vectors, one of the fundamental assumptions is often that vector bites are the sole or main route of host infection. Here, we demonstrate experimentally a transmission route whereby hosts (red grouse, Lagopus lagopus scoticus) became infected with a member of the tick-borne encephalitis virus complex, Louping Ill virus, after eating the infected tick vector. Furthermore, we estimated from field observations that this mode of infection could account for 73-98% of all virus infections in wild red grouse in their first season. This has potential implications for the understanding of other biting vector-borne pathogens where hosts may ingest vectors through foraging or grooming.
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Identifying disease reservoirs in complex systems: mountain hares as reservoirs of ticks and Louping-Ill virus, pathogens of red grouse
Journal of Animal Ecology, 2003Co-Authors: M.k. Laurenson, Lucy Gilbert, Hugh W. Reid, Rachel Norman, Peter J HudsonAbstract:Summary 1 We examined the role of mountain hares in the Louping-Ill virus/Ixodes ricinus tick system to determine whether hares were reservoirs of these pathogens for red grouse. A field experiment, which involved reducing mountain hare densities was undertaken and changes in tick abundance, Louping-Ill virus seroprevalence and red grouse densities recorded. 2 Hares were found to be important hosts for all stages of ticks at two study sites and, where sheep were frequently treated with acaricide, hares fed the greatest proportion of adult ticks. Hare densities were reduced at the experimental site between 1993 and 2001 but remained relatively constant at a control site. Both nymph and larvae tick burdens on red grouse chicks declined over this period to very low levels at the treatment site, but not at the control site. The estimated size of the tick population at the treatment site decreased by more than 99% by 1999. 3 Louping-Ill prevalence, as measured by antibody prevalence in shot young red grouse, also declined at the treatment site, lagging behind the tick decline by approximately 2 years. The number of young grouse produced per hen grouse at this treatment site increased in comparison to a second control area. However, no change was found in summer grouse densities and thus we cannot demonstrate parasite-mediated competition. 4 A deterministic SIR-type model describing the dynamics of this pathogen/vector/host system was constructed and used to examine the role of mountain hares in Louping-Ill virus and tick dynamics. The model predicted a decline in tick numbers and seroprevalence as hare densities reduced. The inclusion of hares as both tick hosts and vector–host–vector transmitters of Louping-Ill virus gave the best fit to the observed data.
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A recombinant Semliki Forest virus particle vaccine encoding the prME and NS1 proteins of Louping Ill virus is effective in a sheep challenge model.
Vaccine, 2001Co-Authors: Margaret M Morris-downes, Hugh W. Reid, Brian J. Sheahan, Marina N. Fleeton, Peter Liljeström, Gregory J. AtkinsAbstract:This study has examined the efficacy following intramuscular administration of a recombinant Semliki Forest virus (rSFV) vaccine, encoding the prME and NS1 proteins of Louping Ill virus (LIV), in sheep. Administration of rSFV-LIV vaccine resulted in transient detection at the injection site and draining lymph node only and no dissemination to distal sites. In addition, the recombinant vaccine offered complete protection against subcutaneous challenge with LIV, and partial protection following intranasal administration of LIV. Protected animals had no pathological changes normally associated with LIV infection, and had developed high antibody titres. In contrast, the two animals not protected exhibited classical clinical signs and neuropathological lesions of LIV infection. These findings indicate that rSFV-based vaccines have the potential to be developed as effective prototype vaccines for LIV.
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Tracing the origins of Louping Ill virus by molecular phylogenetic analysis
Journal of General Virology, 1998Co-Authors: K. Mcguire, Hugh W. Reid, George F. Gao, Edward C. Holmes, E. A. GouldAbstract:The nucleotide and deduced amino acid sequences of Louping Ill (LI) virus isolates, collected from representative regions of the British Isles and Norway, were determined for either the entire envelope gene (20 isolates) or for a portion of the envelope gene that spans a hypervariable region and includes an LI virus specific marker sequence (53 isolates). Phylogenetic analysis reveals the presence of three major geographical populations of LI virus in the British Isles, viz. Irish, Welsh and British LI viruses, which all cause encephalomyelitis in animals, predominantly sheep, and co-habit the same tick population. British LI virus occurs throughout Scotland, England, Ireland and Norway. Irish and Welsh LI viruses occur only in Ireland and Wales, respectively. Phylogenetic analysis also predicts that LI virus initially emerged in Ireland and that a descendant was introduced into Great Britain via Wales and was subsequently transported to the borders of Scotland, from where it was dispersed throughout Scotland, northern England and Norway. More recently, the British LI virus was reintroduced into Ireland and also into south-west England. Dates of lineage divergence, calculated from the synonymous substitution rate, indicate that LI virus emerged in the British Isles less than 800 years ago and most LI virus dispersal occurred during the last 300 years. By combining these data with historical records it appears that livestock movement can be implicated in the dispersal of LI virus.
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THE EPIDEMIOLOGY OF Louping-Ill, A TICK BORNE INFECTION OF RED GROUSE (LAGOPUS LAGOPUS SCOTICUS)
Parassitologia, 1997Co-Authors: Peter J Hudson, Ernest A. Gould, Hugh W. Reid, Linda D. Jones, K. Laurenson, Michael W. Gaunt, Rachel Norman, K. Macguire, David NewbornAbstract:The epidemiology of Louping-Ill in red grouse was studied in northern Britain concentrating on the possible role of other species and mechanisms of disease persistence. This tick borne viral disease caused heavy mortality in red grouse, particularly chicks. Louping-Ill induced mortality reduced the strength of the density dependence that generates the tendency of grouse populations to cycle and in some populations may cause population sinks. Four routes of transmission were examined and non-viraemic transmission of virus between ticks cofeeding on hares was considered significant. Field data supported the hypothesis that disease dynamics is influenced greatly by mountain hares, both as passive amplifiers and as hosts for the tick vector. Genetic variation in Louping-Ill within Britain was small.
Peter J Hudson - One of the best experts on this subject based on the ideXlab platform.
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Ticks need not bite their red grouse hosts to infect them with Louping Ill virus.
Proceedings of the Royal Society of London. Series B: Biological Sciences, 2004Co-Authors: Lucy Gilbert, Hugh W. Reid, Linda D. Jones, M. Karen Laurenson, E. A. Gould, Peter J HudsonAbstract:For pathogens transmitted by biting vectors, one of the fundamental assumptions is often that vector bites are the sole or main route of host infection. Here, we demonstrate experimentally a transmission route whereby hosts (red grouse, Lagopus lagopus scoticus) became infected with a member of the tick-borne encephalitis virus complex, Louping Ill virus, after eating the infected tick vector. Furthermore, we estimated from field observations that this mode of infection could account for 73-98% of all virus infections in wild red grouse in their first season. This has potential implications for the understanding of other biting vector-borne pathogens where hosts may ingest vectors through foraging or grooming.
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Identifying disease reservoirs in complex systems: mountain hares as reservoirs of ticks and Louping-Ill virus, pathogens of red grouse
Journal of Animal Ecology, 2003Co-Authors: M.k. Laurenson, Lucy Gilbert, Hugh W. Reid, Rachel Norman, Peter J HudsonAbstract:Summary 1 We examined the role of mountain hares in the Louping-Ill virus/Ixodes ricinus tick system to determine whether hares were reservoirs of these pathogens for red grouse. A field experiment, which involved reducing mountain hare densities was undertaken and changes in tick abundance, Louping-Ill virus seroprevalence and red grouse densities recorded. 2 Hares were found to be important hosts for all stages of ticks at two study sites and, where sheep were frequently treated with acaricide, hares fed the greatest proportion of adult ticks. Hare densities were reduced at the experimental site between 1993 and 2001 but remained relatively constant at a control site. Both nymph and larvae tick burdens on red grouse chicks declined over this period to very low levels at the treatment site, but not at the control site. The estimated size of the tick population at the treatment site decreased by more than 99% by 1999. 3 Louping-Ill prevalence, as measured by antibody prevalence in shot young red grouse, also declined at the treatment site, lagging behind the tick decline by approximately 2 years. The number of young grouse produced per hen grouse at this treatment site increased in comparison to a second control area. However, no change was found in summer grouse densities and thus we cannot demonstrate parasite-mediated competition. 4 A deterministic SIR-type model describing the dynamics of this pathogen/vector/host system was constructed and used to examine the role of mountain hares in Louping-Ill virus and tick dynamics. The model predicted a decline in tick numbers and seroprevalence as hare densities reduced. The inclusion of hares as both tick hosts and vector–host–vector transmitters of Louping-Ill virus gave the best fit to the observed data.
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THE EPIDEMIOLOGY OF Louping-Ill, A TICK BORNE INFECTION OF RED GROUSE (LAGOPUS LAGOPUS SCOTICUS)
Parassitologia, 1997Co-Authors: Peter J Hudson, Ernest A. Gould, Hugh W. Reid, Linda D. Jones, K. Laurenson, Michael W. Gaunt, Rachel Norman, K. Macguire, David NewbornAbstract:The epidemiology of Louping-Ill in red grouse was studied in northern Britain concentrating on the possible role of other species and mechanisms of disease persistence. This tick borne viral disease caused heavy mortality in red grouse, particularly chicks. Louping-Ill induced mortality reduced the strength of the density dependence that generates the tendency of grouse populations to cycle and in some populations may cause population sinks. Four routes of transmission were examined and non-viraemic transmission of virus between ticks cofeeding on hares was considered significant. Field data supported the hypothesis that disease dynamics is influenced greatly by mountain hares, both as passive amplifiers and as hosts for the tick vector. Genetic variation in Louping-Ill within Britain was small.
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Transmission of Louping Ill virus between infected and uninfected ticks co‐feeding on mountain hares
Medical and veterinary entomology, 1997Co-Authors: Linda D. Jones, Peter J Hudson, Hugh W. Reid, Michael W. Gaunt, Rosie S. Hails, Karen Laurenson, Pauline Henbest, Ernest A. GouldAbstract:Most of the data on oral infection of ticks by Louping Ill virus have been obtained from experiments in which animals were infected by syringe inoculation with infectious material. Using infected ticks to mimic the natural situation, we have demonstrated that Louping Ill (LI) virus transmission can occur from infected to uninfected Ixodes ricinus feeding in close proximity on mountain hares (Lepus timidus). Under these conditions the hares developed either low or undetectable viraemias. Highest prevalence of LI virus infection was observed in recipient nymphs which had fed to repletion between days 3 and 7 post-attachment of virus-infected adults; following engorgement, 56% of nymphs acquired virus. These results demonstrate the efficient transmission of LI virus between co-feeding ticks on naive mountain hares. However, when ticks were allowed to co-feed on virus-immune hares a significant reduction in the frequency of infection was observed. Neither red deer (Cervus elaphus) nor New Zealand White rabbits supported transmission of LI virus. The significance of virus transmission between cofeeding ticks on LI virus epidemiology is discussed.
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Efficacy of acaricidal tags and pour-on as prophylaxis against ticks and Louping-Ill in red grouse.
Medical and Veterinary Entomology, 1997Co-Authors: M.k. Laurenson, Peter J Hudson, Simon J. Thirgood, K. Mcguire, Hugh W. ReidAbstract:This paper examines the efficacy of 10% lambdacyhalothrin-impregnated plastic tags and a deltamethrin pour-on preparation in protecting red grouse chicks from parasitism by ticks and subsequent infection with the Louping-Ill virus. In 1995, ten red grouse hens (Lagopus lagopus scoticus) in a free-living population in north-east Scotland were fitted with lambdacyhalothrin-impregnated plastic tags, glued to radio transmitters. Chicks of more than 10 days of age from a further ten untreated radio-collared hens were caught and fitted with individual tags to the ptagium. Both treatments significantly reduced tick burdens in the short term. The number of larvae and nymphs on chicks up to 45 days was less under both treatments than on control chicks and tagged chicks had fewer nymphs than chicks from treated hens. Nevertheless, treatments did not reduce viral infection rates nor increase survival to 10 weeks, possibly explained by incomplete treatment of tagged broods and/or direct or indirect mortality due to tags. In 1996 chicks in ten broods from hens with radio transmitters were individually treated at 14 days of age at a rate of 1 mg/kg of chick with a deltamethrin pour-on preparation. This preparation significantly reduced the number of larvae and nymphs on grouse chicks 7-10 days after application below the number on untreated controls. At 20 days from application, however, only larval numbers were lower on treated chicks. Nevertheless Louping-Ill virus infection prevalences were significantly reduced at 35 days of age and survival of chicks to 10 weeks increased.
H W Reid - One of the best experts on this subject based on the ideXlab platform.
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Prevalence, spatial distribution and the effect of control measures on Louping-Ill virus in the Forest of Bowland, Lancashire.
Epidemiology and infection, 2007Co-Authors: M.k. Laurenson, H W Reid, Iain J. Mckendrick, R. Challenor, G. K. MathewsonAbstract:The complex pathogen-host-vector system of the tick-borne Louping-Ill virus causes economic losses to sheep and red grouse in upland United Kingdom. This paper examines the spatial distribution, incidence and effect of control measures on Louping-Ill virus in the Bowland Fells of Lancashire. Seroprevalence in sheep at the beginning of the study varied within the area and was affected significantly by the frequency of acaricide treatment. There was a clear decrease over 5 years in the effective force of infection on farms implementing a vaccination programme, irrespective of acaricide treatment regime, however, only one third of farms apparently eliminated infection. On farms where vaccination did not occur or where vaccination was carried out intermittently, the estimated force of infection was variable or possibly increased. Thus, as befits a complex host-pathogen system, reductions in prevalence were not as dramatic as predicted; we discuss the potential explanations for these observations.
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The role of lambs in Louping-Ill virus amplification.
Parasitology, 2000Co-Authors: M.k. Laurenson, David Newborn, H W Reid, I. Pow, R Norman, P J HudsonAbstract:In some areas of Scotland, the prevalence of Louping-Ill virus has not decreased despite the vaccination of replacement ewes for over 30 years. The role of unvaccinated lambs in viral persistence was examined through a combination of an empirical study of infection rates of lambs and mathematical modelling. Serological sampling revealed that most lambs were protected by colostral immunity at turnout in May/June but were fully susceptible by the end of September. Between 8 and 83% of lambs were infected over the first season, with seroconversion rates greater in late rather than early summer. The proportion of lambs that could have amplified the Louping-Ill virus was low, however, because high initial titres of colostral antibody on farms with a high force of infection gave protection for several months. A simple mathematical model suggested that the relationship between the force of infection and the percentage of lambs that became viraemic was not linear and that the maximum percentage of viraemic lambs occurred at moderately high infection rates. Examination of the conditions required for Louping-Ill persistence suggested that the virus could theoretically persist in a sheep flock with over 370 lambs, if the grazing season was longer than 130 days. In practice, however, lamb viraemia is not a general explanation for Louping-Ill virus persistence as these conditions are not met in most management systems and because the widespread use of acaracides in most tick-affected hIll farming systems reduces the number of ticks feeding successfully.
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Definitive identification of Louping Ill virus by RT-PCR and sequencing in field populations of Ixodes ricinus on the Lochindorb Estate
Archives of Virology, 1997Co-Authors: M. W. Gaunt, H W Reid, K. Laurenson, P J Hudson, L. D. Jones, E. A. GouldAbstract:Rapid and precise virus detection procedures are an important component of any epizootiological study. An automated one tube reverse transcriptase and nested primer polymerase chain reaction (RT-PCR) followed by nucleotide sequencing of the cDNA product, was used for the rapid detection and identification of Louping Ill (LI) virus in field caught Ixodes ricinus and compared with a classical isolation method i.e. infectivity in cell culture. The results establish the genetic identity of LI virus on the Lochindorb Estate. There was a high correlation between the results obtained by RT-PCR and infectivity assays. RT-PCR and sequencing proved to be a rapid and accurate system for identifying LI virus in field specimens. Development of this system should improve the capacity to undertake detailed epizootiological studies of LI virus.
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Antigenic similarity of central European encephalitis and Louping-Ill viruses.
Acta Virologica, 1995Co-Authors: Zdeněk Hubálek, H W Reid, Irene Pow, M. H. HussainAbstract:Twenty isolates of Central European encephalitis (CEE) virus were compared with 20 isolates of Louping-Ill (LI) virus in indirect immunofluorescence test (IIFT), using a panel of 17 monoclonal antibodies (MoAbs) prepared against the prototype LI virus. Three Asian members of the tick-borne encephalitis (TBE) complex were also included in the comparison: Turkish sheep encephalitis (TSE), Russian spring-summer encephalitis (RSSE) and Langat (LGT) viruses. Antigenic relationships of the viruses were evaluated by Dice similarity coefficient and cluster analysis. The results revealed antigenic heterogeneity of LI isolates, antigenic homogeneity of CEE isolates, and indicated that CEE and LI are related varieties of Eurasian TBE flavivirus that also includes TSE and RSSE strains.
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persistence and transmission of tick borne viruses ixodes ricinus and Louping Ill virus in red grouse populations
Parasitology, 1995Co-Authors: Peter J Hudson, David Newborn, H W Reid, Ernest A. Gould, Linda D. Jones, Michael W. Gaunt, Rachel Norman, M.k. Laurenson, Roger G Bowers, Andrew P DobsonAbstract:The population dynamics of tick-borne disease agents and in particular the mechanisms which influence their persistence are examined with reference to the flavivirus that causes Louping-Ill in red grouse and sheep. Pockets of infection cause heavy mortality and the infection probably persists as a consequence of immigration of susceptible hosts. Seroprevalence is positively associated with temporal variations in vectors per host, although variation between areas is associated with the abundance of mountain hares. The presence of alternative tick hosts, particularly large mammals, provides additional hosts for increasing tick abundance. Grouse alone can not support the vectors and the pathogen but both can persist when a non-viraemic mammalian host supports the tick population and a sufficiently high number of nymphs bite grouse. These alternative hosts may also amplify virus through non-viraemic transmission by the process of co-feeding, although the relative significance of this has yet to be determined. Another possible route of infection is through the ingestion of vectors when feeding or preening. Trans-ovarial transmission is a potentially important mechanism for virus persistence but has not been recorded with Louping-Ill and Ixodes ricinus. The influence of non-viraemic hosts, both in the multiplication of vectors and the amplification of virus through non-viraemic transmission are considered significant for virus persistence.
M.k. Laurenson - One of the best experts on this subject based on the ideXlab platform.
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Prevalence, spatial distribution and the effect of control measures on Louping-Ill virus in the Forest of Bowland, Lancashire.
Epidemiology and infection, 2007Co-Authors: M.k. Laurenson, H W Reid, Iain J. Mckendrick, R. Challenor, G. K. MathewsonAbstract:The complex pathogen-host-vector system of the tick-borne Louping-Ill virus causes economic losses to sheep and red grouse in upland United Kingdom. This paper examines the spatial distribution, incidence and effect of control measures on Louping-Ill virus in the Bowland Fells of Lancashire. Seroprevalence in sheep at the beginning of the study varied within the area and was affected significantly by the frequency of acaricide treatment. There was a clear decrease over 5 years in the effective force of infection on farms implementing a vaccination programme, irrespective of acaricide treatment regime, however, only one third of farms apparently eliminated infection. On farms where vaccination did not occur or where vaccination was carried out intermittently, the estimated force of infection was variable or possibly increased. Thus, as befits a complex host-pathogen system, reductions in prevalence were not as dramatic as predicted; we discuss the potential explanations for these observations.
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Identifying disease reservoirs in complex systems: mountain hares as reservoirs of ticks and Louping-Ill virus, pathogens of red grouse
Journal of Animal Ecology, 2003Co-Authors: M.k. Laurenson, Lucy Gilbert, Hugh W. Reid, Rachel Norman, Peter J HudsonAbstract:Summary 1 We examined the role of mountain hares in the Louping-Ill virus/Ixodes ricinus tick system to determine whether hares were reservoirs of these pathogens for red grouse. A field experiment, which involved reducing mountain hare densities was undertaken and changes in tick abundance, Louping-Ill virus seroprevalence and red grouse densities recorded. 2 Hares were found to be important hosts for all stages of ticks at two study sites and, where sheep were frequently treated with acaricide, hares fed the greatest proportion of adult ticks. Hare densities were reduced at the experimental site between 1993 and 2001 but remained relatively constant at a control site. Both nymph and larvae tick burdens on red grouse chicks declined over this period to very low levels at the treatment site, but not at the control site. The estimated size of the tick population at the treatment site decreased by more than 99% by 1999. 3 Louping-Ill prevalence, as measured by antibody prevalence in shot young red grouse, also declined at the treatment site, lagging behind the tick decline by approximately 2 years. The number of young grouse produced per hen grouse at this treatment site increased in comparison to a second control area. However, no change was found in summer grouse densities and thus we cannot demonstrate parasite-mediated competition. 4 A deterministic SIR-type model describing the dynamics of this pathogen/vector/host system was constructed and used to examine the role of mountain hares in Louping-Ill virus and tick dynamics. The model predicted a decline in tick numbers and seroprevalence as hare densities reduced. The inclusion of hares as both tick hosts and vector–host–vector transmitters of Louping-Ill virus gave the best fit to the observed data.
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The role of lambs in Louping-Ill virus amplification.
Parasitology, 2000Co-Authors: M.k. Laurenson, David Newborn, H W Reid, I. Pow, R Norman, P J HudsonAbstract:In some areas of Scotland, the prevalence of Louping-Ill virus has not decreased despite the vaccination of replacement ewes for over 30 years. The role of unvaccinated lambs in viral persistence was examined through a combination of an empirical study of infection rates of lambs and mathematical modelling. Serological sampling revealed that most lambs were protected by colostral immunity at turnout in May/June but were fully susceptible by the end of September. Between 8 and 83% of lambs were infected over the first season, with seroconversion rates greater in late rather than early summer. The proportion of lambs that could have amplified the Louping-Ill virus was low, however, because high initial titres of colostral antibody on farms with a high force of infection gave protection for several months. A simple mathematical model suggested that the relationship between the force of infection and the percentage of lambs that became viraemic was not linear and that the maximum percentage of viraemic lambs occurred at moderately high infection rates. Examination of the conditions required for Louping-Ill persistence suggested that the virus could theoretically persist in a sheep flock with over 370 lambs, if the grazing season was longer than 130 days. In practice, however, lamb viraemia is not a general explanation for Louping-Ill virus persistence as these conditions are not met in most management systems and because the widespread use of acaracides in most tick-affected hIll farming systems reduces the number of ticks feeding successfully.
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Efficacy of acaricidal tags and pour-on as prophylaxis against ticks and Louping-Ill in red grouse.
Medical and Veterinary Entomology, 1997Co-Authors: M.k. Laurenson, Peter J Hudson, Simon J. Thirgood, K. Mcguire, Hugh W. ReidAbstract:This paper examines the efficacy of 10% lambdacyhalothrin-impregnated plastic tags and a deltamethrin pour-on preparation in protecting red grouse chicks from parasitism by ticks and subsequent infection with the Louping-Ill virus. In 1995, ten red grouse hens (Lagopus lagopus scoticus) in a free-living population in north-east Scotland were fitted with lambdacyhalothrin-impregnated plastic tags, glued to radio transmitters. Chicks of more than 10 days of age from a further ten untreated radio-collared hens were caught and fitted with individual tags to the ptagium. Both treatments significantly reduced tick burdens in the short term. The number of larvae and nymphs on chicks up to 45 days was less under both treatments than on control chicks and tagged chicks had fewer nymphs than chicks from treated hens. Nevertheless, treatments did not reduce viral infection rates nor increase survival to 10 weeks, possibly explained by incomplete treatment of tagged broods and/or direct or indirect mortality due to tags. In 1996 chicks in ten broods from hens with radio transmitters were individually treated at 14 days of age at a rate of 1 mg/kg of chick with a deltamethrin pour-on preparation. This preparation significantly reduced the number of larvae and nymphs on grouse chicks 7-10 days after application below the number on untreated controls. At 20 days from application, however, only larval numbers were lower on treated chicks. Nevertheless Louping-Ill virus infection prevalences were significantly reduced at 35 days of age and survival of chicks to 10 weeks increased.
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persistence and transmission of tick borne viruses ixodes ricinus and Louping Ill virus in red grouse populations
Parasitology, 1995Co-Authors: Peter J Hudson, David Newborn, H W Reid, Ernest A. Gould, Linda D. Jones, Michael W. Gaunt, Rachel Norman, M.k. Laurenson, Roger G Bowers, Andrew P DobsonAbstract:The population dynamics of tick-borne disease agents and in particular the mechanisms which influence their persistence are examined with reference to the flavivirus that causes Louping-Ill in red grouse and sheep. Pockets of infection cause heavy mortality and the infection probably persists as a consequence of immigration of susceptible hosts. Seroprevalence is positively associated with temporal variations in vectors per host, although variation between areas is associated with the abundance of mountain hares. The presence of alternative tick hosts, particularly large mammals, provides additional hosts for increasing tick abundance. Grouse alone can not support the vectors and the pathogen but both can persist when a non-viraemic mammalian host supports the tick population and a sufficiently high number of nymphs bite grouse. These alternative hosts may also amplify virus through non-viraemic transmission by the process of co-feeding, although the relative significance of this has yet to be determined. Another possible route of infection is through the ingestion of vectors when feeding or preening. Trans-ovarial transmission is a potentially important mechanism for virus persistence but has not been recorded with Louping-Ill and Ixodes ricinus. The influence of non-viraemic hosts, both in the multiplication of vectors and the amplification of virus through non-viraemic transmission are considered significant for virus persistence.
