History matching of a complex epidemiological model of human immunodeficiency virus transmission by using variance emulation.

Complex stochastic models are commonplace in epidemiology, but their utility depends on their calibration to empirical data. History matching is a (pre)calibration method that has been applied successfully to complex deterministic models. In this work, we adapt history matching to stochastic models, by emulating the variance in the model outputs, and therefore accounting for its dependence on the model's input values. The method proposed is applied to a real complex epidemiological model of human immunodeficiency virus in Uganda with 22 inputs and 18 outputs, and is found to increase the efficiency of history matching, requiring 70% of the time and 43% fewer simulator evaluations compared with a previous variant of the method. The insight gained into the structure of the human immunodeficiency virus model, and the constraints placed on it, are then discussed.

Recurrence of bovine tuberculosis breakdowns in Great Britain: risk factors and prediction.

Bovine tuberculosis (bTB) is an important economic disease worldwide with implications for both animal and human health. In Great Britain the number of herds that test positive for bTB, termed "breakdowns", has increased over the last two decades. Despite more intensive testing during a breakdown, around 23% of breakdowns recur within 12 months of the previous breakdown ending, and around 38% within 24 months. These "recurrent" breakdowns may be important for onward transmission of infection. Detailed case-control data were analysed to identify factors associated with recurrence within 12 months. The model predicted 83% of all recurrent breakdowns, with a positive predictive value (PPV) of 44%. A further model, restricted to data currently available nationally, was not sufficient to predict recurrence reliably; at a sensitivity of 72-76%, the PPV was 33-36%, when validated on independent data. Factors identified to be associated with recurrence are consistent with previous studies; namely, the number of reactors, a recent bTB history in the herd and a lack of association with the confirmation status of the initial breakdown. These variables are indicative of a higher level of infection or residual infection, and could be useful in the future development of predictive models for bTB recurrence.

Predicting prolonged bovine tuberculosis breakdowns in Great Britain as an aid to control.

Bovine tuberculosis (bTB) is an important notifiable disease in cattle in Great Britain (GB), and is subject to statutory control measures. Despite this, disease incidence has increased since the mid-1980s, and around 30% of herd breakdowns continue for more than 240 days. This is twice the shortest possible time for confirmed breakdowns to test clear from infection (≈120 days), and four times the shortest possible time for unconfirmed breakdowns (≈60 days). These "prolonged" breakdowns consume substantial resources and may act as an ongoing source of infection. It is not clear why some breakdowns become prolonged. Existing detailed case-control data have been re-analysed to determine risk factors for breakdowns lasting longer than 240 days, the strongest of which was the confirmation status of the breakdown: OR 12.6 (95%CI: 6.7-25.4). A further model restricted to data available early on in a breakdown for all breakdowns nationally, can predict 82-84% of prolonged breakdowns with a positive predictive value of 44-49% when validated using existing national datasets over a 4-year period. Identification of prolonged breakdowns at an earlier stage could help to target bTB controls in GB.

Mortality in a cohort of flat-coated retrievers in the UK.

A cohort study of 174 flat-coated retrievers was undertaken to establish the importance of cancer in flat coat mortality in terms of the prevalence of neoplasia in the breed and also the relative effect of cancer on lifespan in relation to other forms of mortality. Dogs aged 2-7 years were recruited in 1996 and followed until 2007. An annual health census was used to collect the data. Two dogs were lost to follow-up and 72 dogs (42%) died from confirmed neoplasia. Twenty dogs (11.6%) died of unconfirmed tumours and 61 (35%) died from non-neoplastic conditions. The cause of death was unknown for 19 dogs. Soft tissue sarcoma (especially histiocytic sarcoma) was the predominant cancer type, affecting 32 dogs (44% of neoplasms). Six dogs died with malignant melanoma and three with lymphoma. Median age at death was 9 years for dogs with tumours (eight for sarcoma patients) and 12 years for non-neoplastic fatalities. The results confirm that soft tissue sarcoma, particularly histiocytic sarcoma, is a major cause of mortality in this breed.

Infection dynamics: from organ to host population.

A symposium discussing collaborative research work on infectious diseases dynamics was held at Queens' College, University of Cambridge on 25 October 2006.