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Weinert L.A.,University of Cambridge | Chaudhuri R.R.,University of Sheffield | Wang J.,University of Cambridge | Peters S.E.,University of Cambridge | And 26 more authors.
Nature Communications | Year: 2015

Streptococcus suis causes disease in pigs worldwide and is increasingly implicated in zoonotic disease in East and South-East Asia. To understand the genetic basis of disease in S. suis, we study the genomes of 375 isolates with detailed clinical phenotypes from pigs and humans from the United Kingdom and Vietnam. Here, we show that isolates associated with disease contain substantially fewer genes than non-clinical isolates, but are more likely to encode virulence factors. Human disease isolates are limited to a single-virulent population, originating in the 1920, s when pig production was intensified, but no consistent genomic differences between pig and human isolates are observed. There is little geographical clustering of different S. suis subpopulations, and the bacterium undergoes high rates of recombination, implying that an increase in virulence anywhere in the world could have a global impact over a short timescale. © 2015 Macmillan Publishers Limited. All rights reserved.


Pretorius C.,FutuResearch Institute | Menzies N.A.,Center for Health Decision Science | Chindelevitch L.,Harvard University | Cohen T.,Brigham and Women's Hospital | And 11 more authors.
AIDS | Year: 2014

OBJECTIVE(S):: Many countries are considering expanding HIV treatment following recent findings emphasizing the effects of antiretroviral therapy (ART) on reducing HIV transmission in addition to already established survival benefits. Given the close interaction of tuberculosis (TB) and HIV epidemics, ART expansion could have important ramifications for TB burden. Previous studies suggest a wide range of possible TB impacts following ART expansion. We used three independently developed TB-HIV models to estimate the TB-related impact of expanding ART in South Africa. DESIGN:: We considered two dimensions of ART expansion - improving coverage of pre-ART and ART services, and expanding CD4-based ART eligibility criteria (from CD4 <350 to CD4 <500 or all HIV-positive). METHODS:: Three independent mathematical models were calibrated to the same data pertaining to the South African HIV-TB epidemic, and used to assess standardized ART policy changes. Key TB impact indictors were projected from 2014 to 2033. RESULTS:: Compared with current eligibility and coverage, cumulative TB incidence was projected to decline by 6-30% over the period 2014-2033 if ART eligibility were expanded to all HIV positive individuals, and by 28-37% if effective ART coverage were additionally increased to 80%. Overall, expanding ART was estimated to avert one TB case for each 10-13 additional person-years of ART. All models showed that TB incidence and mortality reductions would grow over time, but would stabilize towards the end of the projection period. CONCLUSION:: ART expansion could substantially reduce TB incidence and mortality in South Africa and could provide a platform for collaborative HIV-TB programs to effectively halt HIV-associated TB.


Marshall J.M.,California Institute of Technology | Marshall J.M.,Center for Outbreak Analysis and Modelling
Bioengineered Bugs | Year: 2011

Insects carry out essential ecological functions, such as pollination, but also cause extensive damage to agricultural crops and transmit human diseases such as malaria and dengue fever. Advances in insect transgenesis are making it increasingly feasible to engineer genes conferring desirable phenotypes, and gene drive systems are required to spread these genes into wild populations. Medea provides one solution, being able to spread into a population from very low initial frequencies through the action of a maternally-expressed toxin linked to a zygotically-expressed antidote. Several other toxin-antidote combinations are imaginable that distort the offspring ratio in favor of a desired transgene, or drive the population towards an all-male crash. We explore two such systems-Semele, which is capable of spreading a desired transgene into an isolated population in a confined manner; and Merea, which is capable of inducing a local population crash when located on the Z chromosome of a Lepidopteron pest. © 2011 Landes Bioscience.


Tanabe K.,Osaka University | Mita T.,Tokyo Women's Medical University | Jombart T.,Center for Outbreak Analysis and Modelling | Eriksson A.,University of Cambridge | And 18 more authors.
Current Biology | Year: 2010

Plasmodium falciparum is distributed throughout the tropics and is responsible for an estimated 230 million cases of malaria every year, with a further 1.4 billion people at risk of infection [1-3]. Little is known about the genetic makeup of P. falciparum populations, despite variation in genetic diversity being a key factor in morbidity, mortality, and the success of malaria control initiatives. Here we analyze a worldwide sample of 519 P. falciparum isolates sequenced for two housekeeping genes (63 single nucleotide polymorphisms from around 5000 nucleotides per isolate). We observe a strong negative correlation between within-population genetic diversity and geographic distance from sub-Saharan Africa (R 2 = 0.95) over Africa, Asia, and Oceania. In contrast, regional variation in transmission intensity seems to have had a negligible impact on the distribution of genetic diversity. The striking geographic patterns of isolation by distance observed in P. falciparum mirror the ones previously documented in humans [4-7] and point to a joint sub-Saharan African origin between the parasite and its host. Age estimates for the expansion of P. falciparum further support that anatomically modern humans were infected prior to their exit out of Africa and carried the parasite along during their colonization of the world. © 2010 Elsevier Ltd.


Hollingsworth T.D.,University of Warwick | Pilcher C.D.,San Francisco General Hospital | Hecht F.M.,San Francisco General Hospital | Deeks S.G.,San Francisco General Hospital | Fraser C.,Center for Outbreak Analysis and Modelling
Journal of Infectious Diseases | Year: 2015

We estimate the relative transmission rate in early versus later infection among men who have sex with men (MSM) in San Francisco, California, by studying the characteristics of a sample of transmitters, recruited through newly diagnosed, recently infected MSM between 1996 and 2009. Of 36 transmitters identified, 9 were determined on the basis of testing history and serologic testing to have been recently infected. The unadjusted odds ratio of transmitting during early infection was 15.2 (95% confidence interval [CI], 6.3-33.4; P <. 001); the odds ratio was 8.9 (95% CI, 4.1-19.4) after adjustment for self-reported antiretroviral treatment. This high transmissibility could be due to both high infectiousness and high rates of sex partner change or concurrent partnerships. © 2014 The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.


Read J.M.,University of Liverpool | Edmunds W.J.,London School of Hygiene and Tropical Medicine | Riley S.,Center for Outbreak Analysis and Modelling
Epidemiology and Infection | Year: 2012

A central tenet of close-contact or respiratory infection epidemiology is that infection patterns within human populations are related to underlying patterns of social interaction. Until recently, few researchers had attempted to quantify potentially infectious encounters made between people. Now, however, several studies have quantified social mixing behaviour, using a variety of methods. Here, we review the methodologies employed, suggest other appropriate methods and technologies, and outline future research challenges for this rapidly advancing field of research. © Copyright Cambridge University Press 2012.


Pareek M.,UK National Heart and Lung Institute | Pareek M.,Imperial College London | Abubakar I.,Public Health England | Abubakar I.,University of East Anglia | And 4 more authors.
European Respiratory Journal | Year: 2011

Tuberculosis (TB) primarily occurs in the foreign-born in European countries, such as the UK, where increasing notifications and the high proportion of foreign-born cases has refocused attention on immigrant (new entrant) screening. We investigated how UK primary care organisations (PCOs) screen new entrants and whether this differs according to TB burden in the PCOs (incidence <20 or ≥20 cases per 100,000 per annum). An anonymous, 20-point questionnaire was sent to all 192 UK PCOs asking which new entrants are screened, who is screened for active TB/latent TB infection (LTBI) and the methods used. Descriptive analyses were undertaken. Categorical responses were compared using the Chi-squared test. 177 (92.2%) out of 192 PCOs responded; all undertook screening action in response to abnormal chest radiographs, but only 107 (60.4%) screened new entrants for LTBI. Few new entrants had active TB diagnosed (median 0.0%, interquartile range (IQR) 0.0-0.5%) but more were identified with LTBI (median 7.85%, IQR 4.30-13.50%). High-burden PCOs were significantly less likely to screen new entrants for LTBI (OR 0.26, 95% CI 0.12-0.54; p<0.0001). Among PCOs screening for LTBI, there was substantial deviation from national guidance in selection of new entrant subgroups and screening method. Considerable heterogeneity and deviation from national guidance exist throughout the UK new entrant screening process, with high-burden regions undertaking the least screening. Forming an accurate picture of current front-line practice will help to inform future development of European new entrant screening policy. Copyright©ERS 2011.


Fox J.,King's College London | White P.J.,Public Health England | White P.J.,Center for Outbreak Analysis and Modelling | Garnett G.P.,Center for Outbreak Analysis and Modelling | And 2 more authors.
AIDS | Year: 2011

Background: The risk of acquiring HIV from a single sexual contact varies enormously reflecting biological and behavioural characteristics of both infected and uninfected partners. Accurate information on HIV transmission risk is required to construct evidence-based risk reduction practices for individuals, to direct the provision of prevention strategies at the population level, and enable the definition, quantification and comparison of true exposure in individuals termed 'exposed uninfected' within clinical trials. Methods: Following a systematic review of current literature on HIV transmission estimates, an HIV risk score was developed, incorporating weighted risk factors into a Bernoulli mathematical model, allowing quantification of overall risk of HIV acquisition within HIV-serodiscordant partnerships. Results: The HIV risk score enumerates the relative risk of HIV acquisition from HIV-positive partners incorporating the type and frequency of specific sex acts, the index case HIV plasma viral load and stage of disease, and the presence of genital ulcer disease in either partner and pregnancy, HSV-2 seropositivity, and circumcision status (men only) in the HIV-negative partner. Conclusion: Key determinants of HIV exposure risk can be incorporated into a mathematical model in order to quantify individual relative risks of HIV acquisition. Such a model can facilitate comparisons within clinical trials of exposed uninfected individuals and facilitate interventions to reduce HIV transmission. © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins.


PubMed | University of Amsterdam, Hospital for Tropical Diseases, University of Sheffield, Imperial College London and 7 more.
Type: | Journal: Nature communications | Year: 2015

Streptococcus suis causes disease in pigs worldwide and is increasingly implicated in zoonotic disease in East and South-East Asia. To understand the genetic basis of disease in S. suis, we study the genomes of 375 isolates with detailed clinical phenotypes from pigs and humans from the United Kingdom and Vietnam. Here, we show that isolates associated with disease contain substantially fewer genes than non-clinical isolates, but are more likely to encode virulence factors. Human disease isolates are limited to a single-virulent population, originating in the 1920, s when pig production was intensified, but no consistent genomic differences between pig and human isolates are observed. There is little geographical clustering of different S. suis subpopulations, and the bacterium undergoes high rates of recombination, implying that an increase in virulence anywhere in the world could have a global impact over a short timescale.

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