540 research outputs found
SUPERSEDED - Epidemiological characteristics of human-infective RNA viruses
No full text## This item has been superseded by the one which can be found at https://doi.org/10.7488/ds/2265 . ## RNA viruses are a major threat to human health. Here, based on extensive literature searches carried out over a period of 18 years, we provide a catalogue of all 214 known human-infective RNA virus species. We link these viruses to metadata for a number of traits that influence their epidemiology, including the date of the first report of human infection, transmissibility in human populations, transmission route(s) and host range. This database can be used in comparative studies of human-infective RNA viruses to identify the characteristics of viruses most likely to pose the greatest public health threat, both now and in the future.Filename: Woolhouse and Brierley RNA virus database.xsl
The predicted impact of immunosuppression upon population age-intensity profiles for schistosomiasis.
No full textThe slow development of acquired immunity is thought to be responsible for the characteristic convex age-intensity curve seen in human schistosome infection, which peaks earlier in more heavily infected populations (this is described as a peak shift). Schistosomes are able to suppress protective host responses, and it is hypothesized that this suppression is responsible for the delayed development of protective responses. A deterministic mathematical model is used to describe levels of infection and immunity in an endemic population, incorporating protective immune responses which either reduce adult worm burden or reduce superinfection. Suppression, related to current worm burden, is also included and acts against one or both protective responses. If suppression acts against the entire protective response, it is able to delay the development of protective immunity, and the peak shift is predicted to be reversed at higher infection intensities, with removal of the peaks altogether at the highest levels of infection and/or suppression. If only the anti-adult worm protective immune response is vulnerable to suppression, while the anti-reinfection response remains intact, then suppression does not remove the peak in the age-intensity curve. These findings are discussed in the light of existing field and experimental data
Controlling endemic disease in cattle populations: current challenges and future opportunities
No full textThe British cattle population hosts a diverse community of endemic
pathogens that impact the sustainability of beef and dairy production. As such, there
has been a tremendous amount of ongoing research to develop more cost-effective
strategies for controlling disease at the industry level. Cattle movements have come
under particular scrutiny over the past decade both because of their role in spreading
many economically important diseases and because the movements of individual
cattle in Great Britain have been explicitly recorded in a centralized electronic
database since 1998. Numerous studies have shown that these cattle movements
organize into complex networks with key structural and temporal features that
influence transmission dynamics. Building on previous work, this thesis used a
variety of epidemiological and statistical models to highlight limitations in the
current approaches to controlling disease as well as opportunities for reducing
endemic disease prevalence through targeted interventions. Empirical disease data
from the national bovine tuberculosis (bTB) control programme and from two
seroprevalence studies of bovine viral diarrhoea virus (BVDV) in Scottish cattle
herds were used in conjunction with movement data from the Cattle Tracing System
(CTS) database.
Endemic diseases are often challenging to control due to lack of affordable
and accurate diagnostic tests as well as the presence of subclinically infected carriers
that can easily escape detection. There was evidence that combined issues with the
sensitivity and specificity of routine surveillance methods for bTB were contributing
to a low level of disease transmission within and between Scottish cattle herds from
2002 to 2009. For BVDV, herds that purchased pregnant beef dams, beef dams with
a calf at foot, and open dairy heifers were significantly more likely to be seropositive
even though these movements were responsible for only a small number of network
contacts. In both cases, targeting the subset of high risk movements with disease
specific biosecurity measures may be a more cost-effective use of limited national
disease control resources.
Other researchers have suggested that control strategies should target
multiple diseases simultaneously to reduce trade-offs in resource allocation. Using
key indicators of herd reproductive performance derived from the CTS database, it
was shown that improving the reproductive management of herds operating below
industry standards could reduce endemic disease prevalence by reducing the
movements of replacement breeding cattle. A series of network generation
algorithms were also developed to study the effects of restricting contact formation
based on key demographic and network characteristics of actively trading cattle
farms. Strategies that increased network fragmentation either by forcing highly
connected farms to form contacts with other highly connected farms or preventing
the formation of movements with a high predicted betweenness centrality were
found to be particularly effective in limiting disease transmission.
For these models to be useful in guiding future policy decisions, it is
important to incorporate financial and behavioural drivers of dynamic network
change. Following the introduction of pre- and post-movement testing requirements
for cattle imported into Scotland from endemic bTB regions, there was a significant
decline in cross-border movements, which has likely contributed to the decreasing
risk of bTB outbreaks as much as testing itself. Many endemic cattle diseases such
as BVDV also spread through local transmission mechanisms, which may
undermine the success of disease control programmes that exclusively target cattle
movements. There was also evidence that in the absence of national animal
legislation, few farmers were likely to adopt biosecurity measures against BVDV.
This may be related to the perceived inefficacy of recommendations as well as
general unawareness of farm disease status due to the non-specific clinical signs of
BVDV outbreaks.
Although the CTS database was originally intended for use in slaughter
traceback investigations, results from this thesis show how the basic records of
births, deaths, and movements can be used to generate valuable insights into the
epidemiology of endemic cattle diseases. The findings also emphasize that the
management decisions of individual herds can have a substantial impact on industry
level transmission dynamics, which offers unique opportunities to develop novel and
more cost-effective disease control programmes
Epidemiology of antimicrobial resistance at the livestock-human interface in an urban environment: a One Health approach
No full textLivestock have been implicated as a reservoir for antimicrobial resistant (AMR) bacteria that may spread to humans, with the keeping of livestock widely postulated as a risk factor for AMR in humans. However, quantitative evidence of the role of livestock in the emergence and transmission of AMR bacteria to human populations is lacking. This thesis focuses on the role of livestock keeping as a potentially high-risk interface for AMR transmission between humans and livestock in urban Nairobi. To achieve this, E. coli isolates were systematically collected from sympatric human and livestock populations in 99 households across Nairobi, Kenya. E. coli was characterised both phenotypically (through antimicrobial susceptibility testing) and genetically (through whole genome sequencing). In the first part of this thesis, I conduct a comprehensive systematic review to investigate existing evidence that food animals are responsible for transfer of resistant E. coli and their AMR determinants to humans. I demonstrate that the current evidence regarding transmission of drug resistance between food animals and humans is limited and that similarity of AMR bacteria or AMR determinants in the two populations does not, by itself, provide information on directionality of transfer. I highlight the need to use high resolution genomic analysis on human and livestock bacterial samples collected in time and space to better understand the direction and frequency of AMR transmission between these populations. Next, utilising AMR phenotypes and genotypes, I explored the variation in carriage of AMR E. coli and investigated the role of livestock ownership as a risk factor for AMR carriage in humans. First, I explored the epidemiology of clinically relevant AMR phenotypes and AMR genetic markers. I detected high rates of AMR phenotypes, with 47.6% and 21.1% of isolates displaying resistance to ≥ 3 and ≥5 antimicrobial classes respectively. Whole-genome sequencing revealed 60 acquired genes and 14 point mutations conferring AMR to 9 antimicrobial classes. sul2, strA, strB, tetA, and blaTEM-1B were the most frequently detected AMR genes conferring resistance to sulfonamides, aminoglycosides, tetracyclines, and β-lactams respectively – the most commonly found phenotypes. Highest carriage of AMR genes and phenotypes was observed in humans, pigs and poultry compared to goats, rabbits and bovines. Secondly, I demonstrated that the presence of livestock in the household did not influence phenotypic or genotypic AMR carriage in humans, but the impact of keeping livestock on human AMR carriage was instead influenced by presence of animal manure in the household. Utilising high resolution sequencing data, I proceeded to investigate the patterns of bacterial relatedness and strain sharing as a proxy for transmission potential. I showed that livestock and human isolates are genetically heterogeneous, with minimal evidence of clustering by host group, and that E. coli genomes in humans did not segregate according to livestock ownership. Next, I found evidence of 91 sharing events differing by less than ten base pairs (59 involving livestock isolates only 23 human isolates only, and 9 between humans and livestock), and that most of the sharing events were confined within households with only occasional instances of spread between household. I also demonstrate that high-resolution sequence-based analysis of SNPs is more discriminatory than MLST – a widely used tool in describing transmission of E. coli. Next, I described the patterns of antimicrobial sales in humans and livestock, and the level of awareness and common behaviours related to antimicrobial prescribing amongst human and veterinary pharmacists in urban Nairobi. β- lactams, fluoroquinolones, first and second generation cephalosporins, and metronidazole were the most commonly purchased human antimicrobials while tetracyclines, sulphonamides, penicillins, and macrolides were the most commonly purchased veterinary antimicrobials. This finding was in line with the resistance phenotypes and genotypes described in this thesis. I found that whilst most pharmacists were knowledgeable about antimicrobial use and AMR, inappropriate prescribing practices were common and that over the counter sale of antimicrobials, without a prescription, was a common occurrence in both human and veterinary drug stores. In the final section of the thesis, I investigated the co-occurrence patterns of acquired AMR genes and the role of conjugative plasmids on the epidemiology of AMR spread. I found evidence of co-location of multiple AMR genes in both human and livestock isolates, potentially enabling acquisition and dissemination of multi-drug resistance phenotypes in a single step. I found a diversity of known plasmids and plasmid replicons that were associated with the distribution of acquired AMR genes. To conclude, I discuss the findings of this thesis in the context of the current epidemiology of AMR pathogens at the human-livestock interface and highlight future directions for research on AMR transmission, and discuss implications of my findings for public health. This thesis demonstrates how fine-scale genomic analysis explicitly embedded within an epidemiologically structured sampling framework can be utilized to track bacterial sharing and in the surveillance of AMR prevalence in a low income urban setting. The connectivity of bacteria and their AMR determinants between humans and livestock and the ultimate impacts upon human health lends strong support for a holistic ‘One Health’ perspective for AMR surveillance
SUPERSEDED - Epidemiological characteristics of human-infective RNA viruses
No full text## This data item has been replaced by the one which can be found at https://doi.org/10.7488/ds/2265 . ## RNA viruses are a major threat to human health. Here, based on extensive literature searches carried out over a period of 18 years, we provide a catalogue of all 214 known human-infective RNA virus species. We link these viruses to metadata for a number of traits that influence their epidemiology, including the date of the first report of human infection, transmissibility in human populations, transmission route(s) and host range. This database can be used in comparative studies of human-infective RNA viruses to identify the characteristics of viruses most likely to pose the greatest public health threat, both now and in the future
Systematic review and meta-analysis of the effects of treatment and immunization against schistosomiasis
No full textSchistosomiasis is a water-borne parasitic disease of great public health importance mainly
in sub-Saharan African countries. The majority of current control programmes use the
antihelminthic drug praziquantel to reduce disease burden in endemic areas. Praziquantel
treatment has been reported to accelerate the development of protective immunity against
re-infection that otherwise takes years to develop. To date, there is no licensed vaccine for
schistosomiasis in humans but an attenuated schistosome parasite vaccine has been tested in
animal models.
Employing systematic review and meta-analysis approaches, my PhD research has four main
objectives relating to attenuated schistosome vaccine and praziquantel treatment: 1) to
identify predictors that determine protection levels after treatment with attenuated
Schistosoma mansoni vaccines in the mouse model, 2) to quantify the influence of host and
schistosome parasite species on attenuated parasite vaccine efficacy, 3) to explore the
direction of change (increase/decrease) in schistosome parasite-specific antibody isotypes
after praziquantel treatment in humans, 4) to identify predictors of praziquantel efficacy in
humans.
My analyses revealed three factors that have an influence on the protection levels provided
by attenuated schistosome parasite vaccines: increasing numbers of immunizing parasites
had a positive effect on the levels of protection whereas increasing the radiation dose and the
time to challenge infection had negative effects. Analyses showed that the attenuated
schistosome vaccine has the potential to achieve protection levels as high as 79% after a
single dose in mice. Alongside this, baboon studies consistently reported protective effects of
attenuated schistosome vaccines against re-infection. These results show there is a high
potential for an attenuated schistosome parasite vaccine to be effective in humans.
A meta-analysis of the influence of praziquantel treatment on the direction of change in
schistosome-specific antibody isotypes was conducted. The analysis revealed considerable
variability in the antibodies’ direction of change among populations. The results also
demonstrated an increase of anti-worm IgA and IgE in the majority of studies. These
antibodies have been reported to have a protective effect against re-infection. The
combination of age and infection intensity, and the number of days after treatment were
identified as influential predictors for some antibody isotypes, but there was no single
predictor that consistently affected all antibody isotypes in the same way.
Praziquantel efficacy levels in humans were investigated and the analyses revealed that cure
rates for schistosomiasis increase with praziquantel dose, and were affected by the identity of
the schistosome parasite species (S. mansoni vs. S. haematobium) and the age of the
participants (children: 0-19 years old vs. adults: ≥ 20 years old). There has been no clear
efficacy level reduction over the treatment years (1979-2013) suggesting that praziquantel is
still effective in the treatment of schistosomiasis despite concerns about possible resistance.
The development of a schistosome vaccine will benefit from a closer investigation into the
mechanisms through which protection is acquired in attenuated schistosome parasite vaccine
studies showing high potential efficacy in animal models. Nevertheless, it will take time to
develop a schistosome vaccine for human use. The uptake of the vaccine will be made even
more challenging by the lack of adequate infrastructure in schistosomiasis endemic areas. In
the meantime, close monitoring of praziquantel efficacy levels is necessary to confirm the
effectiveness of schistosomiasis control in endemic areas
Recruiting students for COVID-19 emergency response: Lessons from eight African countries
No full textA questionnaire on recruiting students for COVID-19 emergency response was sent to 9 TIBA countries and 8 responded. The dataset comprises of an excel spreadsheet containing the responses and a word document summarizing the results.Mkenda, Vera; Woolhouse, Mark; Mutapi, Francisca; Banda, Geoffrey. (2020). Recruiting students for COVID-19 emergency response: Lessons from eight African countries, [dataset]. TIBA Partnership Program. University of Edinburgh. https://doi.org/10.7488/ds/2895
Does the negative binomial distribution add up?
No full textThe negative binomial distribution (NBD) is widely used to describe the distribution of parasitic helminths in a number of host individuals and has proved a useful, though possibly overused, empirical and theoretical device. It is therefore important that the limits to the applicability of the NBD be clearly defined. In this paper, Alan Grafen and Mark Woolhouse consider applications of the NBD in situations where either the host or parasite population can be divided into subpopulations of different types (eg. by age, sex or genotype), and they describe the relationships between the frequency distributions relevant to the different subpopulations and those relevant to the total population
Monitoring the spread of antibiotic resistance in wastewater
No full textBACKGROUND: Antibiotic resistant bacterial infections are causing a growing amount of morbidity and mortality. Effective control and prevention relies on good data on the current burden of antibiotic resistance (ABR). Traditional ABR surveillance from phenotypic, passive, hospital-based testing may not adequately represent the resistome of the general population. Wastewater metagenomics has been proposed as a new type of surveillance to overcome this limitation. It generates rich, quantitative information on the bacterial species and resistance genes of a whole community. Large wastewater metagenomic datasets are now available to monitor and explore drivers of ABR in the community. However, questions remain about how to collect, analyse, and interpret these novel datasets. In this thesis, I aimed to 1) address key unknowns in wastewater data, including sources of resistance, environmental resistance dynamics, and what statistical models describe the distribution of the data well, and 2) investigate global and local patterns in wastewater resistance and identify potential community and hospital drivers.
METHODS: I used a systematic review to find evidence in the literature for dissemination of ABR from hospitals to wastewater. I next developed a compartmental transmission model to investigate environmental resistance dynamics and its impact on human ABR levels. I implemented a multi-response statistical model to correlate hospital-based surveillance (EARS-Net) data with resistance gene abundance in sewage samples from around the world analysed with metagenomics by the Global Sewage Surveillance Project. Finally, I used a paired sampling design and multiple statistical methods to compare the resistome of sewage from hospitals, communities, and wastewater treatment plants (WWTPS) in Scotland. I also investigated the links between ABR in humans and antibiotic consumption in the modelling and data analysis chapters.
RESULTS: I found increasing evidence in primary research that resistant bacteria and resistance genes can be disseminated from hospital patients to wastewater and into natural water sources. Modelling the dynamics of ABR in an environmental reservoir indicated that the environment can theoretically influence human ABR levels as much as or more than an animal reservoir, and mitigate intervention impacts. Combining EARS-Net and sewage metagenomic data indicated that some types of ABR are positively correlated in sewage and hospitals (such as aminoglycosides), but many are not (such as vancomycin and aminopenicillins). The paired sampling study demonstrated that hospital and community sewage resistomes are distinct, and WWTPs mostly reflect community sewage resistomes. I found mixed evidence for an impact of antimicrobial consumption on human ABR levels. Overall, the impact of antibiotic consumption at the population level appears to be small in these datasets.
CONCLUSIONS: Wastewater metagenomics is a valuable way of monitoring ABR in the community. It can indicate the composition of the reservoir of ABR in the general population and what drives it. However, hospital rather than mixed municipal effluent may need to be collected to monitor clinical resistance patterns. To make the most of this new source of data more flexible modelling frameworks that account for wastewater metagenomics specific factors such as high dimensionality and overdispersion. Comparing resistance patterns in hospitals to community sewage implied that patients and/or the hospital environment may present unique and strong selection pressures for resistance. Finally, we also show that differential antibiotic consumption alone cannot explain the observed patterns in resistance abundance on the national or international level
Foot-and-mouth disease epidemiology in relation to the physical, social and demographic farming landscape
No full textThe foot-and-mouth disease (FMD) virus poses a considerable threat both to
farmers and to the wider economy should there be a future incursion into the UK.
The most recent large-scale FMD epidemic in the UK was in 2001. Mathematical
models were developed and used during this epidemic to aid decision-making
about how to most effectively control and eliminate it. While the epidemic was
eventually brought to a halt, it resulted in a huge loss of livestock and is estimated
to have cost the UK economy around ¿6 billion. The mathematical models
predicted the overall spatial spread of FMD well, but had low predictive ability
for identifying precisely which farm premises became infected over the course of
the epidemic. This will in part have been due to the stochastic nature of the
models. However, the transmission probability between two farm premises was
represented as the Euclidean distance between their point locations, which is
a crude representation of FMD transmission. Additionally, the premises' point
location data contain inaccuracies, sometimes identifying the farmer's residential
address rather than the farm itself which may be a long way away.
Local FMD transmission occurs via contaminated fomites carried by people or
vehicles between premises, or by infected particles being blown by wind between
proximal fields. Given that these transmission mechanisms are thought to be
related to having close field boundaries, it is possible that some of the inaccuracy
in model predictions is also due to imprecisely representing such transmission. In
this thesis I use fine-scale geographical data of farm premises' field locations to
study the contiguity of premises (where contiguous premises (CPs) are defined as
having field boundaries <15m apart). I demonstrate that the distance between
two premises' point locations does not accurately represent when they are CPs.
Using an area of southern Scotland containing 4767 livestock premises, I compare
the predictions of model simulations using two different model formulations. The
first is one of the original models based on the 2001 outbreak, and the second
is a new model in which transmission probability is related to whether or not
premises were contiguous. The comparison suggests that the premises that became
infected during the course of the simulations were more predictable using
the new model. While it cannot be concluded that this will translate into more
accurate predictions until this can be validated during a future outbreak, it does
suggest that the new model is more predictable in its route through the landscape,
and therefore that it may better reflect local transmission routes than the original
model. Networks based on contiguity of premises were constructed for the same
area of southern Scotland, and showed that 90.6% (n=4318) of the premises in
the area were indirectly connected to one another as part of the Giant Component
(GC). The network metric of 'betweenness' was used to identify premises acting
as bridges between otherwise disconnected sub-populations of premises. It was
found that removing 100 premises with highest betweenness served to fragment
the GC. Model simulations indicated that, even with some longer-range transmission
possible, removing these premises from the network resulted in a large
decrease in mean number of infected premises and outbreak duration. In real
terms, premises removal from the network would mean ensuring these premises
did not become infected by enhanced biosecurity and/or vaccination depending
on policy.
In this thesis I also considered the role of biosecurity practices in shaping FMD
spread. A sample of 200 Scottish farmers were interviewed on their biosecurity
practices, and their biosecurity risk quantified using a biosecurity 'risk score'
developed during the 2007 FMD outbreak in Surrey. Using Moran's I and network
assortativity measures it was found that there did not appear to be any
clustering of biosecurity risk scores on premises. Statistical analysis found no
association between biosecurity risk and the mathematical model's premises' susceptibility
term (which describes the increase in a premises' susceptibility with
increasing numbers of livestock). This suggests that the model's susceptibility
term is not indirectly capturing a general pattern in biosecurity on different sized
farm premises.
Thus, this body of work shows that incorporating a more realistic representation
of premises location into mathematical models, in terms of area (i.e. as fields)
rather than a point, alters predictions of spatial spread. It also demonstrates that
targeted control at a relatively small number of farms could effectively fragment
the farming landscape, and has the potential to considerably reduce the size
of an FMD outbreak. It also demonstrates that variations in premises' FMD
biosecurity risks are unlikely to be indirectly affecting the spatial or demographic
components of the model. This increase in understanding of how geographic,
social and demographic factors relate to FMD spread through the landscape may
enable more effective control of an outbreak, should there be an incursion in the
UK in future
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