Books by Christl Donnelly
Papers by Christl Donnelly
Statistics in Medicine, 1998
The structures of sexual partner networks are important in determining patterns of transmission o... more The structures of sexual partner networks are important in determining patterns of transmission of STDs including HIV. Empirical data on sexual partnerships and sexual partner networks collected through sampling individuals are a non-random sample of partnerships and network structures even if individuals are sampled randomly. This has the potential to bias estimates of measures describing the sexual partner network. In addition, biases may be introduced through non-response and missing data. Using Monte Carlo simulation, we investigate the biases that are introduced in estimates measures of the sexual partner network through three common sampling methods. The results indicate that substantial systematic biases are introduced. The direction and magnitude of these biases suggest that, by ignoring them, the risk for the establishment and persistence of infection in a population may be underestimated.
Epidemiol Infect, 2005
In recent years, the control or eradication of scrapie and any other transmissible spongiform enc... more In recent years, the control or eradication of scrapie and any other transmissible spongiform encephalopathies (TSEs) possibly circulating in the sheep population has become a priority in Britain and elsewhere in Europe. A better understanding of the epidemiology of scrapie would greatly aid the development and evaluation of control and eradication strategies. Here we bound the range of key epidemiological parameters using a combination of relatively detailed pathogenesis and demography data, more limited data on susceptibility and incubation times, and recent survey data on scrapie incidence in Great Britain. These data are simultaneously analysed using mathematical models describing scrapie transmission between sheep and between flocks. Our analysis suggests that occurrence of scrapie in a flock typically provokes changes in flock management that promote termination of the outbreak, such as the adoption of selective breeding, and that a large fraction of cases (possibly over 80 %) goes undetected. We show that the data analysed are consistent with the within-flock reproduction number of scrapie lying in the range 1 . 5-6, consistent with previous epidemiological studies.
Proceedings of The National Academy of Sciences, 2000
British Food Journal, Apr 11, 2013
In response to a paper published in a previous issue of British Food Journal, it criticises the m... more In response to a paper published in a previous issue of British Food Journal, it criticises the methodology of the previous research. Examines the earlier findings on the projected epidemic size of the new variant of Creutzfeldt-Jakob Disease (vCJD) in humans. Argues that the earlier ...
Annals of Actuarial Science, 2012
We use economic indicators to improve the prediction of the number of incurred but not recorded d... more We use economic indicators to improve the prediction of the number of incurred but not recorded disability insurance claims, assuming that there is a link between the number of claims and the chosen economic indicators. We propose a Bayesian model where we model the claims development in three directions: along incurred periods, recording lag periods and calendar periods. A stochastic model of the economic indicators is incorporated into the calendar period development direction. Thus we allow for the impact of the economic environment on the number of claims. Applying the proposed model to data, we illustrate how the inclusion of economic indicators affects the prediction of the number of incurred but not recorded disability claims.
Nature, 2015
Ebola emerged in West Africa around December 2013 and swept through Guinea, Sierra Leone and Libe... more Ebola emerged in West Africa around December 2013 and swept through Guinea, Sierra Leone and Liberia, giving rise to 27,748 confirmed, probable and suspected cases reported by 29 July 2015. Case diagnoses during the epidemic have relied on polymerase chain reaction-based tests. Owing to limited laboratory capacity and local transport infrastructure, the delays from sample collection to test results being available have often been 2 days or more. Point-of-care rapid diagnostic tests offer the potential to substantially reduce these delays. We review Ebola rapid diagnostic tests approved by the World Health Organization and those currently in development. Such rapid diagnostic tests could allow early triaging of patients, thereby reducing the potential for nosocomial transmission. In addition, despite the lower test accuracy, rapid diagnostic test-based diagnosis may be beneficial in some contexts because of the reduced time spent by uninfected individuals in health-care settings where they may be at increased risk of infection; this also frees up hospital beds. We use mathematical modelling to explore the potential benefits of diagnostic testing strategies involving rapid diagnostic tests alone and in combination with polymerase chain reaction testing. Our analysis indicates that the use of rapid diagnostic tests with sensitivity and specificity comparable with those currently under development always enhances control, whether evaluated at a health-care-unit or population level. If such tests had been available throughout the recent epidemic, we estimate, for Sierra Leone, that their use in combination with confirmatory polymerase chain-reaction testing might have reduced the scale of the epidemic by over a third.
For diseases with some level of associated mortality, the case fatality ratio measures the propor... more For diseases with some level of associated mortality, the case fatality ratio measures the proportion of diseased individuals who die from the disease. In principle, it is straightforward to estimate this quantity from individual follow-up data that provides times from onset to death or recovery. In particular, in a competing risks context, the case fatality ratio is defined by the limiting value of the sub-distribution function, F(1)(t) = Pr(T <or=t and J = 1), associated with death, as t --> infinity, where T denotes the time from onset to death (J = 1) or recovery (J = 2). When censoring is present, however, estimation of F(1)(infinity) is complicated by the possibility of little information regarding the right tail of F(1), requiring use of estimators of F(1)(t(*)) or F(1)(t(*))/(F(1)(t(*))+F(2)(t(*))) where t(*) is large, with F(2)(t) = Pr(T <or=t and J = 2) being the analogous sub-distribution function associated with recovery. With right censored data, the variability of such estimators increases as t(*) increases, suggesting the possibility of using estimators at lower values of t(*) where bias may be increased but overall mean squared error be smaller. These issues are investigated here for non-parametric estimators of F(1) and F(2). The ideas are illustrated on case fatality data for individuals infected with Severe Acute Respiratory Syndrome (SARS) in Hong Kong in 2003.
Proceedings of the Royal Society of London Series B Biological Sciences, Oct 1, 1997
An analysis is presented of the results of a cohort study designed to test whether or not the aet... more An analysis is presented of the results of a cohort study designed to test whether or not the aetiological agent of bovine spongiform encephalopathy (BSE) in cattle can be transmitted maternally (vertically) from dam to o¡spring. Various genetic models are ¢tted to the data under the assumption that the results could be explained entirely by genetic predisposition to disease (as opposed to maternal transmission) given exposure of o¡spring of diseased and una¡ected dams to contaminated cattle feed. The analyses suggest that the results could be explained by the hypothesis of genetic predisposition, provided a large di¡erence exists in the susceptibility of resistant and susceptible hosts, and explore the ranges of genotypic parameters and frequencies consistent with the limited currently available data. The results presented are broadly robust, even under the scenario that a portion of the observed maternally enhanced risk of BSE is due to a low level of maternal transmission in late incubation stage dams.
Philosophical Transactions of the Royal Society of London Series B Biological Sciences, Jul 29, 1997
Mathematical models that describe the key processes determining the pattern of the bovine spongif... more Mathematical models that describe the key processes determining the pattern of the bovine spongiform encephalopathy (BSE) epidemic in British cattle are derived that allow for infection from feed as well as maternal and direct horizontal transmission. Heterogeneous susceptibility classes are also incorporated into the analysis. Maximum likelihood methods are used to estimate parameters and to obtain confidence intervals from available experimental and epidemiological data. A comprehensive sensitivity analysis of all model parameters and distributional assumptions is presented. Additional validation is provided by fitting the model to independent data collected in Northern Ireland. Model estimates and predictions based on BSE case data for Great Britain and Northern Ireland, together with their implications, are reviewed, and future research priorities discussed.
PLOS Neglected Tropical Diseases, 2015
Aedes aegypti, the principal vector of dengue fever, have been genetically engineered for use in ... more Aedes aegypti, the principal vector of dengue fever, have been genetically engineered for use in a sterile insect control programme. To improve our understanding of the dispersal ecology of mosquitoes and to inform appropriate release strategies of 'genetically sterile' male Aedes aegypti detailed knowledge of the dispersal ability of the released insects is needed.
PLOS Neglected Tropical Diseases, 2015
The increasing burden of dengue, and the relative failure of traditional vector control programs ... more The increasing burden of dengue, and the relative failure of traditional vector control programs highlight the need to develop new control methods. SIT using self-limiting genetic technology is one such promising method. A self-limiting strain of Aedes aegypti, OX513A, has already reached the stage of field evaluation. Sustained releases of OX513A Ae. aegypti males led to 80% suppression of a target wild Ae. aegypti population in the Cayman Islands in 2010. Here we describe sustained series of field releases of OX513A Ae. aegypti males in a suburb of Juazeiro, Bahia, Brazil. This study spanned over a year and reduced the local Ae. aegypti population by 95% (95% CI: 92.2%-97.5%) based on adult trap data and 81% (95% CI: 74.9-85.2%) based on ovitrap indices compared to the adjacent norelease control area. The mating competitiveness of the released males (0.031; 95% CI: 0.025-0.036) was similar to that estimated in the Cayman trials (0.059; 95% CI: 0.011 -0.210), indicating that environmental and target-strain differences had little impact on the mating success of the OX513A males. We conclude that sustained release of OX513A males may be an effective and widely useful method for suppression of the key dengue vector Ae. aegypti. The observed level of suppression would likely be sufficient to prevent dengue epidemics in the locality tested and other areas with similar or lower transmission.
Genetical Research, 2000
Polymerase chain reaction (PCR)-based genotyping of oocysts dissected from mosquito midguts has p... more Polymerase chain reaction (PCR)-based genotyping of oocysts dissected from mosquito midguts has previously been used to investigate overall levels of inbreeding within malaria parasite populations. We present a re-analysis of the population structure of Plasmodium falciparum malaria using diploid genotypes at three antigen-encoding loci in 118 oocysts dissected from 34 mosquitoes. We use these data to ask whether mating is occurring at random within the mosquito midgut, as is generally assumed. We observe a highly significant deficit of heterozygous oocysts within mosquitoes at all three loci, suggesting that fusion of gametes occurs non-randomly in the mosquito gut. A variety of biological explanations, such as interrupted feeding of mosquitoes, positive assortative mating and outcrossing depression, could account for this observation. However, an alternative artefactual explanation – the presence of non-amplifying or null alleles – can account for the observed data equally well, w...
PLoS neglected tropical diseases, 2015
Estimating the case-fatality risk (CFR)-the probability that a person dies from an infection give... more Estimating the case-fatality risk (CFR)-the probability that a person dies from an infection given that they are a case-is a high priority in epidemiologic investigation of newly emerging infectious diseases and sometimes in new outbreaks of known infectious diseases. The data available to estimate the overall CFR are often gathered for other purposes (e.g., surveillance) in challenging circumstances. We describe two forms of bias that may affect the estimation of the overall CFR-preferential ascertainment of severe cases and bias from reporting delays-and review solutions that have been proposed and implemented in past epidemics. Also of interest is the estimation of the causal impact of specific interventions (e.g., hospitalization, or hospitalization at a particular hospital) on survival, which can be estimated as a relative CFR for two or more groups. When observational data are used for this purpose, three more sources of bias may arise: confounding, survivorship bias, and sele...
Vaccine, Jan 4, 2015
The most advanced dengue vaccine candidate is a live-attenuated recombinant vaccine containing th... more The most advanced dengue vaccine candidate is a live-attenuated recombinant vaccine containing the four dengue viruses on the yellow fever vaccine backbone (CYD-TDV) developed by Sanofi Pasteur. Several analyses have been published on the safety and immunogenicity of the CYD-TDV vaccine from single trials but none modelled the heterogeneity observed in the antibody responses elicited by the vaccine. We analyse the immunogenicity data collected in five phase-2 trials of the CYD-TDV vaccine. We provide a descriptive analysis of the aggregated datasets and fit the observed post-vaccination PRNT50 titres against the four dengue (DENV) serotypes using multivariate regression models. We find that the responses to CYD-TDV are principally predicted by the baseline immunological status against DENV, but the trial is also a significant predictor. We find that the CYD-TDV vaccine generates similar titres against all serotypes following the third dose, though DENV4 is immunodominant after the f...
Scientific Data, 2015
The unprecedented scale of the Ebola outbreak in West Africa has, as of 29 April 2015, resulted i... more The unprecedented scale of the Ebola outbreak in West Africa has, as of 29 April 2015, resulted in more than 10,884 deaths among 26,277 cases. Prior to the ongoing outbreak, Ebola virus disease (EVD) caused relatively small outbreaks (maximum outbreak size 425 in Gulu, Uganda) in isolated populations in central Africa. Here, we have compiled a comprehensive database of estimates of epidemiological parameters based on data from past outbreaks, including the incubation period distribution, case fatality rate, basic reproduction number (R 0 ), effective reproduction number (R t ) and delay distributions. We have compared these to parameter estimates from the ongoing outbreak in West Africa. The ongoing outbreak, because of its size, provides a unique opportunity to better understand transmission patterns of EVD. We have not performed a meta-analysis of the data, but rather summarize the estimates by virus from comprehensive investigations of EVD and Marburg outbreaks over the past 40 years. These estimates can be used to parameterize transmission models to improve understanding of initial spread of EVD outbreaks and to inform surveillance and control guidelines.
Nature, Jan 10, 2000
... | Article | PubMed | ISI | ChemPort |. Top of page. Wellcome Trust Centre for the Epidemiolog... more ... | Article | PubMed | ISI | ChemPort |. Top of page. Wellcome Trust Centre for the Epidemiology of Infectious Disease, University of Oxford, Oxford OX1 3FY, UK. Correspondence to: Neil M. Ferguson 1 e-mail: Email: [email protected]. Top of page. ...
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Books by Christl Donnelly
Papers by Christl Donnelly