PMCC PMCC

Search tips
Search criteria

Advanced
Results 1-25 (39)
 

Clipboard (0)
None

Select a Filter Below

Journals
more »
Year of Publication
1.  Continent-wide panmixia of an African fruit bat facilitates transmission of potentially zoonotic viruses 
Nature communications  2013;4:10.1038/ncomms3770.
The straw-coloured fruit bat, Eidolon helvum, is Africa’s most widely distributed and commonly hunted fruit bat, often living in close proximity to human populations. This species has been identified as a reservoir of potentially zoonotic viruses, but uncertainties remain regarding viral transmission dynamics and mechanisms of persistence. Here we combine genetic and serological analyses of populations across Africa, to determine the extent of epidemiological connectivity among E. helvum populations. Multiple markers reveal panmixia across the continental range, at a greater geographical scale than previously recorded for any other mammal, whereas populations on remote islands were genetically distinct. Multiple serological assays reveal antibodies to henipaviruses and Lagos bat virus in all locations, including small isolated island populations, indicating that factors other than population size and connectivity may be responsible for viral persistence. Our findings have potentially important public health implications, and highlight a need to avoid disturbances which may precipitate viral spillover.
doi:10.1038/ncomms3770
PMCID: PMC3836177  PMID: 24253424
2.  Bat Flight and Zoonotic Viruses 
Emerging Infectious Diseases  2014;20(5):741-745.
High metabolism and body temperatures of flying bats might enable them to host many viruses.
Bats are sources of high viral diversity and high-profile zoonotic viruses worldwide. Although apparently not pathogenic in their reservoir hosts, some viruses from bats severely affect other mammals, including humans. Examples include severe acute respiratory syndrome coronaviruses, Ebola and Marburg viruses, and Nipah and Hendra viruses. Factors underlying high viral diversity in bats are the subject of speculation. We hypothesize that flight, a factor common to all bats but to no other mammals, provides an intensive selective force for coexistence with viral parasites through a daily cycle that elevates metabolism and body temperature analogous to the febrile response in other mammals. On an evolutionary scale, this host–virus interaction might have resulted in the large diversity of zoonotic viruses in bats, possibly through bat viruses adapting to be more tolerant of the fever response and less virulent to their natural hosts.
doi:10.3201/eid2005.130539
PMCID: PMC4012789  PMID: 24750692
bats; body temperature; Chiroptera; emerging zoonotic viruses; fever; flight; metabolic rate; mammals
3.  Inferring the inter-host transmission of influenza A virus using patterns of intra-host genetic variation 
Influenza A viruses (IAVs) cause acute, highly transmissible infections in a wide range of animal species. Understanding how these viruses are transmitted within and between susceptible host populations is critical to the development of effective control strategies. While viral gene sequences have been used to make inferences about IAV transmission dynamics at the epidemiological scale, their utility in accurately determining patterns of inter-host transmission in the short-term—i.e. who infected whom—has not been strongly established. Herein, we use intra-host sequence data from the viral HA1 (hemagglutinin) gene domain from two transmission studies employing different IAV subtypes in their natural hosts—H3N8 in horses and H1N1 in pigs—to determine how well these data recapitulate the known pattern of inter-host transmission. Although no mutations were fixed over the course of either experimental transmission chain, we show that some minor, transient alleles can provide evidence of host-to-host transmission and, importantly, can be distinguished from those that cannot.
doi:10.1098/rspb.2012.2173
PMCID: PMC3574438  PMID: 23135678
influenza A virus; transmission; evolution; phylogeny; phylodynamics
4.  Quantifying the Impact of Immune Escape on Transmission Dynamics of Influenza 
Science (New York, N.Y.)  2009;326(5953):726-728.
Influenza virus evades prevailing natural and vaccine-induced immunity by accumulating antigenic change in the haemagglutinin surface protein. Linking amino acid substitutions in haemagglutinin epitopes to epidemiology has been problematic because of the scarcity of data connecting these scales. We use experiments on equine influenza virus to address this issue, quantifying how key parameters of viral establishment and shedding increase the probability of transmission with genetic distance between previously immunizing virus and challenge virus. Qualitatively similar patterns emerge from analyses based on antigenic distance and from a published human influenza study. Combination of the equine data and epidemiological models allows us to calculate the effective reproductive number of transmission as a function of relevant genetic change in the virus, illuminating the probability of influenza epidemics as a function of immunity.
doi:10.1126/science.1175980
PMCID: PMC3800096  PMID: 19900931
5.  A restatement of the natural science evidence base relevant to the control of bovine tuberculosis in Great Britain† 
Bovine tuberculosis (bTB) is a very important disease of cattle in Great Britain, where it has been increasing in incidence and geographical distribution. In addition to cattle, it infects other species of domestic and wild animals, in particular the European badger (Meles meles). Policy to control bTB is vigorously debated and contentious because of its implications for the livestock industry and because some policy options involve culling badgers, the most important wildlife reservoir. This paper describes a project to provide a succinct summary of the natural science evidence base relevant to the control of bTB, couched in terms that are as policy-neutral as possible. Each evidence statement is placed into one of four categories describing the nature of the underlying information. The evidence summary forms the appendix to this paper and an annotated bibliography is provided in the electronic supplementary material.
doi:10.1098/rspb.2013.1634
PMCID: PMC3757986  PMID: 23926157
bovine tuberculosis; epidemiology; cattle; badgers; vaccination
6.  Evolution of Equine Influenza Virus in Vaccinated Horses 
Journal of Virology  2013;87(8):4768-4771.
Influenza A viruses are characterized by their ability to evade host immunity, even in vaccinated individuals. To determine how prior immunity shapes viral diversity in vivo, we studied the intra- and interhost evolution of equine influenza virus in vaccinated horses. Although the level and structure of genetic diversity were similar to those in naïve horses, intrahost bottlenecks may be more stringent in vaccinated animals, and mutations shared among horses often fall close to putative antigenic sites.
doi:10.1128/JVI.03379-12
PMCID: PMC3624384  PMID: 23388708
7.  Evidence for multiple waves of global transmission within the seventh cholera pandemic 
Nature  2011;477(7365):462-465.
Vibrio cholerae is a globally important pathogen that is endemic in many areas of the world and causes 3-5 million reported cases of cholera every year (http://www.who.int/wer). Historically there have been seven acknowledged cholera pandemics; included in the 7th and ongoing pandemic are the recent outbreaks in Zimbabwe and Haiti1. Only serogroup O1 isolates (consisting of two biotypes known as ‘classical’ and ‘El Tor’) and the derivative O1392,3 can cause epidemic cholera2. It is believed that the first six cholera pandemics were caused by the classical biotype but El Tor has subsequently spread globally and replaced the classical biotype in the current pandemic1. Detailed molecular epidemiological mapping of cholera has been compromised by a reliance on sub-genomic regions such as mobile elements to infer relationships, making El Tor isolates associated with the 7th pandemic appear superficially diverse. To understand the underlying phylogeny of the lineage responsible for the current pandemic we identified high resolution markers (single nucleotide polymorphisms; SNPs) in 154 whole genome sequences of globally and temporally representative V. cholerae isolates. Using this phylogeny we show that the 7th pandemic has spread from the Bay of Bengal in at least three independent but overlapping waves with a common ancestor in the 1950’s and identify multiple transcontinental transmission events. Additionally, we show how the acquisition of the SXT family of antibiotic resistance elements has shaped the pandemic spread and show that it was first acquired at least 10 years prior to its discovery in V. cholerae.
doi:10.1038/nature10392
PMCID: PMC3736323  PMID: 21866102
8.  Where are the horses? With the sheep or cows? Uncertain host location, vector-feeding preferences and the risk of African horse sickness transmission in Great Britain 
Understanding the influence of non-susceptible hosts on vector-borne disease transmission is an important epidemiological problem. However, investigation of its impact can be complicated by uncertainty in the location of the hosts. Estimating the risk of transmission of African horse sickness (AHS) in Great Britain (GB), a virus transmitted by Culicoides biting midges, provides an insightful example because: (i) the patterns of risk are expected to be influenced by the presence of non-susceptible vertebrate hosts (cattle and sheep) and (ii) incomplete information on the spatial distribution of horses is available because the GB National Equine Database records owner, rather than horse, locations. Here, we combine land-use data with available horse owner distributions and, using a Bayesian approach, infer a realistic distribution for the location of horses. We estimate the risk of an outbreak of AHS in GB, using the basic reproduction number (R0), and demonstrate that mapping owner addresses as a proxy for horse location significantly underestimates the risk. We clarify the role of non-susceptible vertebrate hosts by showing that the risk of disease in the presence of many hosts (susceptible and non-susceptible) can be ultimately reduced to two fundamental factors: first, the abundance of vectors and how this depends on host density, and, second, the differential feeding preference of vectors among animal species.
doi:10.1098/rsif.2013.0194
PMCID: PMC3645429  PMID: 23594817
epidemiology; dilution effect; vector-borne disease; basic reproduction number; Culicoides
9.  Demography of straw-colored fruit bats in Ghana 
Journal of mammalogy  2012;93(5):1393-1404.
Eidolon helvum is widely distributed across sub-Saharan Africa where it forms large, dense colonies. The species is migratory and satellite telemetry studies have demonstrated that individuals can migrate over 2,500 km. It is a common source of bush meat in West Africa and evidence of infection with potentially zoonotic viruses has been found in West African colonies. The species, therefore, is of interest to both ecologists and those interested in public health. Despite this, demographic parameters of the species are unknown. We focused our study primarily on a colony of up to 1,000,000 bats that roost in trees in Accra, Ghana to obtain estimates of birth rate and survival probability. Aging of bats by examination of tooth cementum annuli allowed use of life tables to indicate an annual survival probability for juveniles of 0.43 (95% confidence interval [CI] 0.16–0.77) and for adults of 0.83 (95% CI 0.73–0.93). Additionally, an annual adult survival probability of 0.63 (95% CI 0.27–0.88) was estimated by following 98 radiocollared bats over a year; capture–recapture data were analyzed using multistate models to address the confounding factor of emigration. True survival probabilities may be in between the 2 estimates, because permanent emigration may lead to underestimation in the capture–recapture study, and population decline may lead to overestimation in the life table analysis. Birth rates (0.96 young per female per year, 95% CI 0.92–0.98) and colony size changes were also estimated. Estimation of these key parameters will allow future analyses of both infection dynamics within, and harvest sustainability of, E. helvum populations.
doi:10.1644/11-MAMM-A-270.1
PMCID: PMC3605799  PMID: 23525358
capture–recapture; Eidolon helvum; multistate model; population dynamics; survival; tooth cementum
10.  A framework for the study of zoonotic disease emergence and its drivers: spillover of bat pathogens as a case study 
Many serious emerging zoonotic infections have recently arisen from bats, including Ebola, Marburg, SARS-coronavirus, Hendra, Nipah, and a number of rabies and rabies-related viruses, consistent with the overall observation that wildlife are an important source of emerging zoonoses for the human population. Mechanisms underlying the recognized association between ecosystem health and human health remain poorly understood and responding appropriately to the ecological, social and economic conditions that facilitate disease emergence and transmission represents a substantial societal challenge. In the context of disease emergence from wildlife, wildlife and habitat should be conserved, which in turn will preserve vital ecosystem structure and function, which has broader implications for human wellbeing and environmental sustainability, while simultaneously minimizing the spillover of pathogens from wild animals into human beings. In this review, we propose a novel framework for the holistic and interdisciplinary investigation of zoonotic disease emergence and its drivers, using the spillover of bat pathogens as a case study. This study has been developed to gain a detailed interdisciplinary understanding, and it combines cutting-edge perspectives from both natural and social sciences, linked to policy impacts on public health, land use and conservation.
doi:10.1098/rstb.2012.0228
PMCID: PMC3427567  PMID: 22966143
bat; zoonosis; emergence; collaborative framework
11.  Ebola Virus Antibodies in Fruit Bats, Ghana, West Africa 
Emerging Infectious Diseases  2012;18(7):1207-1209.
doi:10.3201/eid1807.111654
PMCID: PMC3376795  PMID: 22710257
viruses; Ebola virus; Ebolavirus sp.; Reston Ebola virus; REBOV; Zaire Ebola virus; ZEBOV; African fruit bats; Africa; Epomops franqueti; Epomophorus gambianus; Hypsignathus monstrosus; Nanonycteris veldkampii; Eidolon helvum; viruses; Ghana
12.  Dynamics of Salmonella infection of macrophages at the single cell level 
Salmonella enterica causes a range of diseases. Salmonellae are intracellular parasites of macrophages, and the control of bacteria within these cells is critical to surviving an infection. The dynamics of the bacteria invading, surviving, proliferating in and killing macrophages are central to disease pathogenesis. Fundamentally important parameters, however, such as the cellular infection rate, have not previously been calculated. We used two independent approaches to calculate the macrophage infection rate: mathematical modelling of Salmonella infection experiments, and analysis of real-time video microscopy of infection events. Cells repeatedly encounter salmonellae, with the bacteria often remain associated with the macrophage for more than ten seconds. Once Salmonella encounters a macrophage, the probability of that bacterium infecting the cell is remarkably low: less than 5%. The macrophage population is heterogeneous in terms of its susceptibility to the first infection event. Once infected, a macrophage can undergo further infection events, but these reinfection events occur at a lower rate than that of the primary infection.
doi:10.1098/rsif.2012.0163
PMCID: PMC3427505  PMID: 22552918
Salmonella; macrophage; dynamic; infection rate; Holling's type II
13.  Factors Associated with Pleurisy in Pigs: A Case-Control Analysis of Slaughter Pig Data for England and Wales 
PLoS ONE  2012;7(2):e29655.
A case-control investigation was undertaken to determine management and health related factors associated with pleurisy in slaughter pigs in England and Wales.
Methods
The British Pig Executive Pig Health Scheme database of abattoir pathology was used to identify 121 case (>10% prevalence of pleurisy on 3 or more assessment dates in the preceding 24 months) and 121 control units (≤5% prevalence of pleurisy on 3 or more assessment dates in the preceding 24 months). Farm data were collected by postal questionnaire. Data from respondents (70 cases and 51 controls) were analysed using simple logistic regression models with Bonferroni corrections. Limited multivariate analyses were also performed to check the robustness of the overall conclusions.
Results and Conclusions
Management factors associated with increased odds of pleurisy included no all-in all-out pig flow (OR 9.3, 95% confidence interval [CI]: 3.3–29), rearing of pigs with an age difference of >1 month in the same airspace (OR 6.5 [2.8–17]) and repeated mixing (OR 2.2 [1.4–3.8]) or moving (OR 2.2 [1.5–3.4]) of pigs during the rearing phase. Those associated with decreased odds of pleurisy included filling wean-to-finish or grower-to-finish systems with piglets from ≤3 sources (OR 0.18 [0.07–0.41]) compared to farrow-to-finish systems, cleaning and disinfecting of grower (ORs 0.28 [0.13–0.61] and 0.29 [0.13–0.61]) and finisher (ORs 0.24 [0.11–0.51] and 0.2 [0.09–0.44]) accommodation between groups, and extended down time of grower and finisher accommodation (OR 0.84 [0.75–0.93] and 0.86 [0.77–0.94] respectively for each additional day of downtime). This study demonstrated the value of national-level abattoir pathology data collection systems for case control analyses and generated guidance for on-farm interventions to help reduce the prevalence of pleurisy in slaughter pigs.
doi:10.1371/journal.pone.0029655
PMCID: PMC3281815  PMID: 22363407
14.  Genome-Scale Evolution and Phylodynamics of Equine H3N8 Influenza A Virus▿† 
Journal of Virology  2011;85(11):5312-5322.
Equine influenza viruses (EIVs) of the H3N8 and H7N7 subtypes are the causative agents of an important disease of horses. While EIV H7N7 apparently is extinct, H3N8 viruses have circulated for more than 50 years. Like human influenza viruses, EIV H3N8 caused a transcontinental pandemic followed by further outbreaks and epidemics, even in populations with high vaccination coverage. Recently, EIV H3N8 jumped the species barrier to infect dogs. Despite its importance as an agent of infectious disease, the mechanisms that underpin the evolutionary and epidemiological dynamics of EIV are poorly understood, particularly at a genomic scale. To determine the evolutionary history and phylodynamics of EIV H3N8, we conducted an extensive analysis of 82 complete viral genomes sampled during a 45-year span. We show that both intra- and intersubtype reassortment have played a major role in the evolution of EIV, and we suggest that intrasubtype reassortment resulted in enhanced virulence while heterosubtypic reassortment contributed to the extinction of EIV H7N7. We also show that EIV evolves at a slower rate than other influenza viruses, even though it seems to be subject to similar immune selection pressures. However, a relatively high rate of amino acid replacement is observed in the polymerase acidic (PA) segment, with some evidence for adaptive evolution. Most notably, an analysis of viral population dynamics provided evidence for a major population bottleneck of EIV H3N8 during the 1980s, which we suggest resulted from changes in herd immunity due to an increase in vaccination coverage.
doi:10.1128/JVI.02619-10
PMCID: PMC3094979  PMID: 21430049
15.  A universal real-time assay for the detection of Lyssaviruses 
Journal of Virological Methods  2011;177(1-24):87-93.
Highlights
► Universal real-time PCR primer pair demonstrated to hybridize to and detect each of the known Lyssaviruses (including Rabies virus) with greater sensitivity than a standard pan-Lyssavirus hemi-nested RT-PCR typically used. ► Target sequences of bat derived virus species unavailable for analysis (Aravan-, Khujand-, Irkut-, West Caucasian bat- and Shimoni bat virus) were synthesized to produce oligonucleotides and the synthetic DNA was used as a target for primer hybridization.
Rabies virus (RABV) is enzootic throughout most of the world. It is now widely accepted that RABV had its origins in bats. Ten of the 11 Lyssavirus species recognised, including RABV, have been isolated from bats. There is, however, a lack of understanding regarding both the ecology and host reservoirs of Lyssaviruses. A real-time PCR assay for the detection of all Lyssaviruses using universal primers would be beneficial for Lyssavirus surveillance. It was shown that using SYBR® Green, a universal real-time PCR primer pair previously demonstrated to detect European bat Lyssaviruses 1 and 2, and RABV, was able to detect reverse transcribed RNA for each of the seven virus species available to us. Target sequences of bat derived virus species unavailable for analysis were synthesized to produce oligonucleotides. Lagos Bat-, Duvenhage- and Mokola virus full nucleoprotein gene clones enabled a limit of 5–50 plasmid copies to be detected. Five copies of each of the synthetic DNA oligonucleotides of Aravan-, Khujand-, Irkut-, West Caucasian bat- and Shimoni bat virus were detected. The single universal primer pair was therefore able to detect each of the most divergent known Lyssaviruses with great sensitivity.
doi:10.1016/j.jviromet.2011.07.002
PMCID: PMC3191275  PMID: 21777619
Lyssavirus; Rabies; Bat; SYBR Green; Real-time PCR; Synthetic DNA
16.  Antibodies to Henipavirus or Henipa-Like Viruses in Domestic Pigs in Ghana, West Africa 
PLoS ONE  2011;6(9):e25256.
Henipaviruses, Hendra virus (HeV) and Nipah virus (NiV), have Pteropid bats as their known natural reservoirs. Antibodies against henipaviruses have been found in Eidolon helvum, an old world fruit bat species, and henipavirus-like nucleic acid has been detected in faecal samples from E. helvum in Ghana. The initial outbreak of NiV in Malaysia led to over 265 human encephalitis cases, including 105 deaths, with infected pigs acting as amplifier hosts for NiV during the outbreak. We detected non-neutralizing antibodies against viruses of the genus Henipavirus in approximately 5% of pig sera (N = 97) tested in Ghana, but not in a small sample of other domestic species sampled under a E. helvum roost. Although we did not detect neutralizing antibody, our results suggest prior exposure of the Ghana pig population to henipavirus(es). Because a wide diversity of henipavirus-like nucleic acid sequences have been found in Ghanaian E. helvum, we hypothesise that these pigs might have been infected by henipavirus(es) sufficiently divergent enough from HeVor NiV to produce cross-reactive, but not cross-neutralizing antibodies to HeV or NiV.
doi:10.1371/journal.pone.0025256
PMCID: PMC3178620  PMID: 21966471
17.  A Bayesian Approach to Analyse Genetic Variation within RNA Viral Populations 
PLoS Computational Biology  2011;7(3):e1002027.
The development of modern and affordable sequencing technologies has allowed the study of viral populations to an unprecedented depth. This is of particular interest for the study of within-host RNA viral populations, where variation due to error-prone polymerases can lead to immune escape, antiviral resistance and adaptation to new host species. Methods to sequence RNA virus genomes include reverse transcription (RT) and polymerase chain reaction (PCR). RT-PCR is a molecular biology technique widely used to amplify DNA from an RNA template. The method itself relies on the in vitro synthesis of copy DNA from RNA followed by multiple cycles of DNA amplification. However, this method introduces artefactual errors that can act as confounding factors when the sequence data are analysed. Although there are a growing number of published studies exploring the intra- and inter-host evolutionary dynamics of RNA viruses, the complexity of the methods used to generate sequences makes it difficult to produce probabilistic statements about the likely sources of observed sequence variants. This complexity is further compounded as both the depth of sequencing and the length of the genome segment of interest increase. Here we develop a Bayesian method to characterise and differentiate between likely structures for the background viral population. This approach can then be used to identify nucleotide sites that show evidence of change in the within-host viral population structure, either over time or relative to a reference sequence (e.g. an inoculum or another source of infection), or both, without having to build complex evolutionary models. Identification of these sites can help to inform the design of more focussed experiments using molecular biology tools, such as site-directed mutagenesis, to assess the function of specific amino acids. We illustrate the method by applying to datasets from experimental transmission of equine influenza, and a pre-clinical vaccine trial for HIV-1.
Author Summary
Characterising genetic variation in viral populations can have important implications in terms of understanding how viruses evolve within infected hosts. Modern sequencing technologies allow genetic information to be obtained faster, more affordably, and in much greater quantities than before. This allows new experimental procedures to be designed to explore aspects of pathogenesis that were previously unattainable, particularly with regard to mutations that occur at particular nucleotide sites that may confer a fitness advantage to the pathogen. This information can be used to study important issues such as the development of antiviral resistance, virulence, and/or changes in host-range specificity. Nonetheless, the experimental procedures used to generate the data can incorporate artefactual errors, and in order to optimise the information obtained from these studies techniques are required to characterise which sites exhibit mutations that may alter viral fitness. As both the depth of sequencing increases and the length of the region sequenced increases (e.g. moves to whole genomes rather than smaller segments), large numbers of sites will exhibit some form of variation, and hence development of a probabilistic method to define and extract these sites-of-interest becomes more important. We tackle this problem here using a Bayesian framework.
doi:10.1371/journal.pcbi.1002027
PMCID: PMC3068928  PMID: 21483482
18.  Intrahost Evolutionary Dynamics of Canine Influenza Virus in Naïve and Partially Immune Dogs ▿  
Journal of Virology  2010;84(10):5329-5335.
The patterns and dynamics of evolution in acutely infecting viruses within individual hosts are largely unknown. To this end, we investigated the intrahost variation of canine influenza virus (CIV) during the course of experimental infections in naïve and partially immune dogs and in naturally infected dogs. Tracing sequence diversity in the gene encoding domain 1 of the hemagglutinin (HA1) protein over the time course of infection provided information on the patterns and processes of intrahost viral evolution and revealed some of the effects of partial host immunity. Viral populations sampled on any given day were generally characterized by mean pairwise genetic diversities between 0.1 and 0.2% and by mutational spectra that changed considerably on different days. Some observed mutations may have affected antigenicity or host range, including reversions of CIV host-associated mutations. Patterns of sequence diversity differed between naïve and vaccinated dogs, with some presumably antigenic mutations transiently reaching high frequency in the latter. CIV populations are therefore characterized by the rapid generation and clearance of genetic diversity. Potentially advantageous mutations arise readily during the course of single infections and may give rise to antigenic escape or host range variants.
doi:10.1128/JVI.02469-09
PMCID: PMC2863817  PMID: 20219907
19.  Dynamics of Influenza Virus Infection and Pathology▿  
Journal of Virology  2010;84(8):3974-3983.
A key question in pandemic influenza is the relative roles of innate immunity and target cell depletion in limiting primary infection and modulating pathology. Here, we model these interactions using detailed data from equine influenza virus infection, combining viral and immune (type I interferon) kinetics with estimates of cell depletion. The resulting dynamics indicate a powerful role for innate immunity in controlling the rapid peak in virus shedding. As a corollary, cells are much less depleted than suggested by a model of human influenza based only on virus-shedding data. We then explore how differences in the influence of viral proteins on interferon kinetics can account for the observed spectrum of virus shedding, immune response, and influenza pathology. In particular, induction of high levels of interferon (“cytokine storms”), coupled with evasion of its effects, could lead to severe pathology, as hypothesized for some fatal cases of influenza.
doi:10.1128/JVI.02078-09
PMCID: PMC2849502  PMID: 20130053
20.  Long-Term Survival of an Urban Fruit Bat Seropositive for Ebola and Lagos Bat Viruses 
PLoS ONE  2010;5(8):e11978.
Ebolaviruses (EBOV) (family Filoviridae) cause viral hemorrhagic fevers in humans and non-human primates when they spill over from their wildlife reservoir hosts with case fatality rates of up to 90%. Fruit bats may act as reservoirs of the Filoviridae. The migratory fruit bat, Eidolon helvum, is common across sub-Saharan Africa and lives in large colonies, often situated in cities. We screened sera from 262 E. helvum using indirect fluorescent tests for antibodies against EBOV subtype Zaire. We detected a seropositive bat from Accra, Ghana, and confirmed this using western blot analysis. The bat was also seropositive for Lagos bat virus, a Lyssavirus, by virus neutralization test. The bat was fitted with a radio transmitter and was last detected in Accra 13 months after release post-sampling, demonstrating long-term survival. Antibodies to filoviruses have not been previously demonstrated in E. helvum. Radio-telemetry data demonstrates long-term survival of an individual bat following exposure to viruses of families that can be highly pathogenic to other mammal species. Because E. helvum typically lives in large urban colonies and is a source of bushmeat in some regions, further studies should determine if this species forms a reservoir for EBOV from which spillover infections into the human population may occur.
doi:10.1371/journal.pone.0011978
PMCID: PMC2915915  PMID: 20694141
21.  The Spread of Bluetongue Virus Serotype 8 in Great Britain and Its Control by Vaccination 
PLoS ONE  2010;5(2):e9353.
Background
Bluetongue (BT) is a viral disease of ruminants transmitted by Culicoides biting midges and has the ability to spread rapidly over large distances. In the summer of 2006, BTV serotype 8 (BTV-8) emerged for the first time in northern Europe, resulting in over 2000 infected farms by the end of the year. The virus subsequently overwintered and has since spread across much of Europe, causing tens of thousands of livestock deaths. In August 2007, BTV-8 reached Great Britain (GB), threatening the large and valuable livestock industry. A voluntary vaccination scheme was launched in GB in May 2008 and, in contrast with elsewhere in Europe, there were no reported cases in GB during 2008.
Methodology/Principal Findings
Here, we use carefully parameterised mathematical models to investigate the spread of BTV in GB and its control by vaccination. In the absence of vaccination, the model predicted severe outbreaks of BTV, particularly for warmer temperatures. Vaccination was predicted to reduce the severity of epidemics, with the greatest reduction achieved for high levels (95%) of vaccine uptake. However, even at this level of uptake the model predicted some spread of BTV. The sensitivity of the predictions to vaccination parameters (time to full protection in cattle, vaccine efficacy), the shape of the transmission kernel and temperature dependence in the transmission of BTV between farms was assessed.
Conclusions/Significance
A combination of lower temperatures and high levels of vaccine uptake (>80%) in the previously-affected areas are likely to be the major contributing factors in the control achieved in England in 2008. However, low levels of vaccination against BTV-8 or the introduction of other serotypes could result in further, potentially severe outbreaks in future.
doi:10.1371/journal.pone.0009353
PMCID: PMC2825270  PMID: 20179768
22.  A Modeling Framework to Describe the Transmission of Bluetongue Virus within and between Farms in Great Britain 
PLoS ONE  2009;4(11):e7741.
Background
Recently much attention has been given to developing national-scale micro-simulation models for livestock diseases that can be used to predict spread and assess the impact of control measures. The focus of these models has been on directly transmitted infections with little attention given to vector-borne diseases such as bluetongue, a viral disease of ruminants transmitted by Culicoides biting midges. Yet BT has emerged over the past decade as one of the most important diseases of livestock.
Methodology/Principal Findings
We developed a stochastic, spatially-explicit, farm-level model to describe the spread of bluetongue virus (BTV) within and between farms. Transmission between farms was modeled by a generic kernel, which includes both animal and vector movements. Once a farm acquired infection, the within-farm dynamics were simulated based on the number of cattle and sheep kept on the farm and on local temperatures. Parameter estimates were derived from the published literature and using data from the outbreak of bluetongue in northern Europe in 2006. The model was validated using data on the spread of BTV in Great Britain during 2007. The sensitivity of model predictions to the shape of the transmission kernel was assessed.
Conclusions/Significance
The model is able to replicate the dynamics of BTV in Great Britain. Although uncertainty remains over the precise shape of the transmission kernel and certain aspects of the vector, the modeling approach we develop constitutes an ideal framework in which to incorporate these aspects as more and better data become available. Moreover, the model provides a tool with which to examine scenarios for the spread and control of BTV in Great Britain.
doi:10.1371/journal.pone.0007741
PMCID: PMC2767512  PMID: 19890400
23.  Evidence of Henipavirus Infection in West African Fruit Bats 
PLoS ONE  2008;3(7):e2739.
Henipaviruses are emerging RNA viruses of fruit bat origin that can cause fatal encephalitis in man. Ghanaian fruit bats (megachiroptera) were tested for antibodies to henipaviruses. Using a Luminex multiplexed microsphere assay, antibodies were detected in sera of Eidolon helvum to both Nipah (39%, 95% confidence interval: 27–51%) and Hendra (22%, 95% CI: 11–33%) viruses. Virus neutralization tests further confirmed seropositivity for 30% (7/23) of Luminex positive serum samples. Our results indicate that henipavirus is present within West Africa.
doi:10.1371/journal.pone.0002739
PMCID: PMC2453319  PMID: 18648649
24.  Antibodies against Lagos Bat Virus in Megachiroptera from West Africa 
Emerging Infectious Diseases  2008;14(6):926-928.
To investigate the presence of Lagos bat virus (LBV)–specific antibodies in megachiroptera from West Africa, we conducted fluorescent antibody virus neutralization tests. Neutralizing antibodies were detected in Eidolon helvum (37%), Epomophorus gambianus (3%), and Epomops buettikoferi (33%, 2/6) from Ghana. These findings confirm the presence of LBV in West Africa.
doi:10.3201/eid1406.071421
PMCID: PMC2600291  PMID: 18507903
Lagos Bat Virus; rabies; megachiroptera; bat; Lyssavirus; dispatch
25.  Assessing the risk of bluetongue to UK livestock: uncertainty and sensitivity analyses of a temperature-dependent model for the basic reproduction number 
Since 1998 bluetongue virus (BTV), which causes bluetongue, a non-contagious, insect-borne infectious disease of ruminants, has expanded northwards in Europe in an unprecedented series of incursions, suggesting that there is a risk to the large and valuable British livestock industry. The basic reproduction number, R0, provides a powerful tool with which to assess the level of risk posed by a disease. In this paper, we compute R0 for BTV in a population comprising two host species, cattle and sheep. Estimates for each parameter which influences R0 were obtained from the published literature, using those applicable to the UK situation wherever possible. Moreover, explicit temperature dependence was included for those parameters for which it had been quantified. Uncertainty and sensitivity analyses based on Latin hypercube sampling and partial rank correlation coefficients identified temperature, the probability of transmission from host to vector and the vector to host ratio as being most important in determining the magnitude of R0. The importance of temperature reflects the fact that it influences many processes involved in the transmission of BTV and, in particular, the biting rate, the extrinsic incubation period and the vector mortality rate.
doi:10.1098/rsif.2007.1110
PMCID: PMC2497440  PMID: 17638649
bluetongue; epidemiology; basic reproduction number; model; sensitivity analysis; uncertainty analysis

Results 1-25 (39)