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Kathryn J. Allan

Bio: Kathryn J. Allan is an academic researcher from University of Glasgow. The author has contributed to research in topics: Leptospira & Leptospirosis. The author has an hindex of 11, co-authored 31 publications receiving 804 citations. Previous affiliations of Kathryn J. Allan include Nottingham University Hospitals NHS Trust & Royal Veterinary College.

Papers
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Journal ArticleDOI
TL;DR: This study suggests that NS4 plays an important role in virus-host interaction and is one of the mechanisms played, at least by BTV-8, to counteract the antiviral response of the host.
Abstract: Bluetongue virus (BTV) is the causative agent of a major disease of livestock (bluetongue). For over two decades, it has been widely accepted that the 10 segments of the dsRNA genome of BTV encode for 7 structural and 3 non-structural proteins. The non-structural proteins (NS1, NS2, NS3/NS3a) play different key roles during the viral replication cycle. In this study we show that BTV expresses a fourth non-structural protein (that we designated NS4) encoded by an open reading frame in segment 9 overlapping the open reading frame encoding VP6. NS4 is 77–79 amino acid residues in length and highly conserved among several BTV serotypes/strains. NS4 was expressed early post-infection and localized in the nucleoli of BTV infected cells. By reverse genetics, we showed that NS4 is dispensable for BTV replication in vitro, both in mammalian and insect cells, and does not affect viral virulence in murine models of bluetongue infection. Interestingly, NS4 conferred a replication advantage to BTV-8, but not to BTV-1, in cells in an interferon (IFN)-induced antiviral state. However, the BTV-1 NS4 conferred a replication advantage both to a BTV-8 reassortant containing the entire segment 9 of BTV-1 and to a BTV-8 mutant with the NS4 identical to the homologous BTV-1 protein. Collectively, this study suggests that NS4 plays an important role in virus-host interaction and is one of the mechanisms played, at least by BTV-8, to counteract the antiviral response of the host. In addition, the distinct nucleolar localization of NS4, being expressed by a virus that replicates exclusively in the cytoplasm, offers new avenues to investigate the multiple roles played by the nucleolus in the biology of the cell.

239 citations

Journal ArticleDOI
TL;DR: It is hypothesized that applying One Health interventions to tackle these health challenges will help to build trust, community engagement and cross-sectoral collaboration, which will in turn strengthen the capacity of fragile health systems to respond to the threat of emerging zoonoses and other future health challenges.
Abstract: Emerging zoonoses with pandemic potential are a stated priority for the global health security agenda, but endemic zoonoses also have a major societal impact in low-resource settings. Although many...

124 citations

Journal ArticleDOI
TL;DR: A ‘One Health’ approach is advocated to promote multidisciplinary research efforts to improve understanding of the animal to human transmission of leptospirosis on the African continent.
Abstract: Leptospirosis is an important but neglected bacterial zoonosis that has been largely overlooked in Africa. In this systematic review, we aimed to summarise and compare current knowledge of: (1) the geographic distribution, prevalence, incidence and diversity of acute human leptospirosis in Africa; and (2) the geographic distribution, host range, prevalence and diversity of Leptospira spp. infection in animal hosts in Africa. Following Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines, we searched for studies that described (1) acute human leptospirosis and (2) pathogenic Leptospira spp. infection in animals. We performed a literature search using eight international and regional databases for English and non-English articles published between January 1930 to October 2014 that met out pre-defined inclusion criteria and strict case definitions. We identified 97 studies that described acute human leptospirosis (n = 46) or animal Leptospira infection (n = 51) in 26 African countries. The prevalence of acute human leptospirosis ranged from 2 3% to 19 8% (n = 11) in hospital patients with febrile illness. Incidence estimates were largely restricted to the Indian Ocean islands (3 to 101 cases per 100,000 per year (n = 6)). Data from Tanzania indicate that human disease incidence is also high in mainland Africa (75 to 102 cases per 100,000 per year). Three major species (Leptospira borgpetersenii, L. interrogans and L. kirschneri) are predominant in reports from Africa and isolates from a diverse range of serogroups have been reported in human and animal infections. Cattle appear to be important hosts of a large number of Leptospira serogroups in Africa, but few data are available to allow comparison of Leptospira infection in linked human and animal populations. We advocate a 'One Health' approach to promote multidisciplinary research efforts to improve understanding of the animal to human transmission of leptospirosis on the African continent.

111 citations

Journal ArticleDOI
TL;DR: It is shown that reassortment in BTV is very flexible, and there is no fundamental barrier to the reassortment of any genome segment.
Abstract: Coinfection of a cell by two different strains of a segmented virus can give rise to a “reassortant” with phenotypic characteristics that might differ from those of the parental strains. Bluetongue virus (BTV) is a double-stranded RNA (dsRNA) segmented virus and the cause of bluetongue, a major infectious disease of livestock. BTV exists as at least 26 different serotypes (BTV-1 to BTV-26). Prompted by the isolation of a field reassortant between BTV-1 and BTV-8, we systematically characterized the process of BTV reassortment. Using a reverse genetics approach, our study clearly indicates that any BTV-1 or BTV-8 genome segment can be rescued in the heterologous “backbone.” To assess phenotypic variation as a result of reassortment, we examined viral growth kinetics and plaque sizes in in vitro experiments and virulence in an experimental mouse model of bluetongue disease. The monoreassortants generated had phenotypes that were very similar to those of the parental wild-type strains both in vitro and in vivo. Using a forward genetics approach in cells coinfected with BTV-1 and BTV-8, we have shown that reassortants between BTV-1 and BTV-8 are generated very readily. After only four passages in cell culture, we could not detect wild-type BTV-1 or BTV-8 in any of 140 isolated viral plaques. In addition, most of the isolated reassortants contained heterologous VP2 and VP5 structural proteins, while only 17% had homologous VP2 and VP5 proteins. Our study has shown that reassortment in BTV is very flexible, and there is no fundamental barrier to the reassortment of any genome segment. Given the propensity of BTV to reassort, it is increasingly important to have an alternative classification system for orbiviruses.

98 citations

Journal ArticleDOI
TL;DR: Results indicate that ruminant livestock are important hosts of Leptospira in northern Tanzania and additional work is needed to understand the role of livestock in the maintenance and transmission of Leptonospira infection in this region and to examine linkages between human and livestock infections.
Abstract: Leptospirosis is a zoonotic bacterial disease that affects more than one million people worldwide each year. Human infection is acquired through direct or indirect contact with the urine of an infected animal. A wide range of animals including rodents and livestock may shed Leptospira bacteria and act as a source of infection for people. In the Kilimanjaro Region of northern Tanzania, leptospirosis is an important cause of acute febrile illness, yet relatively little is known about animal hosts of Leptospira infection in this area. The roles of rodents and ruminant livestock in the epidemiology of leptospirosis were evaluated through two linked studies. A cross-sectional study of peri-domestic rodents performed in two districts with a high reported incidence of human leptospirosis found no evidence of Leptospira infection among rodent species trapped in and around randomly selected households. In contrast, pathogenic Leptospira infection was detected in 7.08% cattle (n = 452 [5.1–9.8%]), 1.20% goats (n = 167 [0.3–4.3%]) and 1.12% sheep (n = 89 [0.1–60.0%]) sampled in local slaughterhouses. Four Leptospira genotypes were detected in livestock. Two distinct clades of L. borgpetersenii were identified in cattle as well as a clade of novel secY sequences that showed only 95% identity to known Leptospira sequences. Identical L. kirschneri sequences were obtained from qPCR-positive kidney samples from cattle, sheep and goats. These results indicate that ruminant livestock are important hosts of Leptospira in northern Tanzania. Infected livestock may act as a source of Leptospira infection for people. Additional work is needed to understand the role of livestock in the maintenance and transmission of Leptospira infection in this region and to examine linkages between human and livestock infections.

70 citations


Cited by
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Book ChapterDOI
01 Jan 2010

5,842 citations

01 Jan 2012
TL;DR: The questionnaires from the field were received, checked and stored by the data processing personnel and checked the completeness of the questionnaires and the correct bubbling.
Abstract: The questionnaires from the field were received, checked and stored by the data processing personnel. They checked: 1. The completeness of the questionnaires 2. The correct bubbling 3. The correct number of questionnaires per household, if total males + total females > 8 as the questionnaire ONLY accommodated maximum of 8 household members. 4. The reference number appears in all the 10 pages of the questionnaires.

1,200 citations

Journal ArticleDOI
TL;DR: Leptospirosis is among the leading zoonotic causes of morbidity worldwide and accounts for numbers of deaths, which approach or exceed those for other causes of haemorrhagic fever.
Abstract: Background Leptospirosis, a spirochaetal zoonosis, occurs in diverse epidemiological settings and affects vulnerable populations, such as rural subsistence farmers and urban slum dwellers. Although leptospirosis is a life-threatening disease and recognized as an important cause of pulmonary haemorrhage syndrome, the lack of global estimates for morbidity and mortality has contributed to its neglected disease status. Methodology/Principal Findings We conducted a systematic review of published morbidity and mortality studies and databases to extract information on disease incidence and case fatality ratios. Linear regression and Monte Carlo modelling were used to obtain age and gender-adjusted estimates of disease morbidity for countries and Global Burden of Disease (GBD) and WHO regions. We estimated mortality using models that incorporated age and gender-adjusted disease morbidity and case fatality ratios. The review identified 80 studies on disease incidence from 34 countries that met quality criteria. In certain regions, such as Africa, few quality assured studies were identified. The regression model, which incorporated country-specific variables of population structure, life expectancy at birth, distance from the equator, tropical island, and urbanization, accounted for a significant proportion (R2 = 0.60) of the variation in observed disease incidence. We estimate that there were annually 1.03 million cases (95% CI 434,000–1,750,000) and 58,900 deaths (95% CI 23,800–95,900) due to leptospirosis worldwide. A large proportion of cases (48%, 95% CI 40–61%) and deaths (42%, 95% CI 34–53%) were estimated to occur in adult males with age of 20–49 years. Highest estimates of disease morbidity and mortality were observed in GBD regions of South and Southeast Asia, Oceania, Caribbean, Andean, Central, and Tropical Latin America, and East Sub-Saharan Africa. Conclusions/Significance Leptospirosis is among the leading zoonotic causes of morbidity worldwide and accounts for numbers of deaths, which approach or exceed those for other causes of haemorrhagic fever. Highest morbidity and mortality were estimated to occur in resource-poor countries, which include regions where the burden of leptospirosis has been underappreciated

1,090 citations

DOI
15 Jun 1977
TL;DR: In 1915 some Japanese Investigators associated a slender coiled oigan with a severe febrile attack, usually accompanied by jaundice, that occurred in both cPiclemic and sporadic form in Japan, this 0rganism they recovered from the blood and patients during life, and from the kidneys post mortem.
Abstract: Asevere type of jaundice that appeared in epidemic form was described by Adolf W eil of " eisbaden in 1880, and from this time for some years there was a tendency to refer to all cases ? severe jaundice that appeared in epidemic !?nn as Weil's disease. In 1915 some Japanese Investigators associated a slender coiled oiganwith a severe febrile attack, usually accompanied by jaundice, that occurred in both cPiclemic and sporadic form in Japan, this 0rganism they recovered from the blood and **** ^ Patients during life, and from the livci 'n(> kidneys post mortem.

696 citations

Journal ArticleDOI
TL;DR: It is argued that these interfaces represent a critical point for cross-species transmission and emergence of pathogens into new host populations, and thus understanding their form and function is necessary to identify suitable interventions to mitigate the risk of disease emergence.
Abstract: Urbanization is characterized by rapid intensification of agriculture, socioeconomic change, and ecological fragmentation, which can have profound impacts on the epidemiology of infectious disease Here, we review current scientific evidence for the drivers and epidemiology of emerging wildlife-borne zoonoses in urban landscapes, where anthropogenic pressures can create diverse wildlife–livestock–human interfaces We argue that these interfaces represent a critical point for cross-species transmission and emergence of pathogens into new host populations, and thus understanding their form and function is necessary to identify suitable interventions to mitigate the risk of disease emergence To achieve this, interfaces must be studied as complex, multihost communities whose structure and form are dictated by both ecological and anthropological factors

403 citations