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Biomedical subjects

Neil M Ferguson

Publications and source records attributed to Neil M Ferguson.

At least 19 recordsLinked to original sources
PubMed2005

The epidemiological impact of antiretroviral use predicted by mathematical models: a review.

This review summarises theoretical studies attempting to assess the population impact of antiretroviral therapy (ART) use on mortality and HIV incidence. We describe the key parameters that determine the impact of therapy, and argue that mathematical models of disease transmission are the natural framework within which to explore the interaction between antiviral use and the dynamics of an HIV epidemic. Our review focuses on the potential effects of ART in resource-poor settings. We discuss choice of model type and structure, the potential for risk behaviour change following widespread introduction of ART, the importance of the stage of HIV infection at which treatment is initiated, and the potential for spread of drug resistance. These issues are illustrated with results from models of HIV transmission. We demonstrate that HIV transmission models predicting the impact of ART use should incorporate a realistic progression through stages of HIV infection in order to capture the effect of the timing of treatment initiation on disease spread. The realism of existing models falls short of properly reproducing patterns of diagnosis timing, incorporating heterogeneity in sexual behaviour, and describing the evolution and transmission of drug resistance. The uncertainty surrounding certain effects of ART, such as changes in sexual behaviour and transmission of ART-resistant HIV strains, demands exploration of best and worst case scenarios in modelling, but this must be complemented by surveillance and behavioural surveys to quantify such effects in settings where ART is implemented.

Journal Article↗
PubMed2005

Strategies for containing an emerging influenza pandemic in Southeast Asia.

Highly pathogenic H5N1 influenza A viruses are now endemic in avian populations in Southeast Asia, and human cases continue to accumulate. Although currently incapable of sustained human-to-human transmission, H5N1 represents a serious pandemic threat owing to the risk of a mutation or reassortment generating a virus with increased transmissibility. Identifying public health interventions that might be able to halt a pandemic in its earliest stages is therefore a priority. Here we use a simulation model of influenza transmission in Southeast Asia to evaluate the potential effectiveness of targeted mass prophylactic use of antiviral drugs as a containment strategy. Other interventions aimed at reducing population contact rates are also examined as reinforcements to an antiviral-based containment policy. We show that elimination of a nascent pandemic may be feasible using a combination of geographically targeted prophylaxis and social distancing measures, if the basic reproduction number of the new virus is below 1.8. We predict that a stockpile of 3 million courses of antiviral drugs should be sufficient for elimination. Policy effectiveness depends critically on how quickly clinical cases are diagnosed and the speed with which antiviral drugs can be distributed.

Age Distribution↗
PubMed2004

The impact of cross-immunity, mutation and stochastic extinction on pathogen diversity.

We examine the dynamics of antigenically diverse infectious agents using a mathematical model describing the transmission dynamics of arbitrary numbers of pathogen strains, interacting via cross-immunity, and in the presence of mutations generating new strains and stochastic extinctions of existing ones. Equilibrium dynamics fall into three classes depending on cross-immunity, transmissibility and host population size: systems where global extinction is likely, stable single-strain persistence, and multiple-strain persistence with stable diversity. Where multi-strain dynamics are stable, a diversity threshold region separates a low-prevalence, low-diversity region of parameter space from a high-diversity, high-prevalence region. The location of the threshold region is determined by the reproduction number of the pathogen and the intensity of cross-immunity, with the sharpness of the transition being determined by the manner in which immunity accrues with repeated infections. Host population size and cross-immunity are found to be the most decisive factors in determining pathogen diversity. While the model framework developed is simplified, we show that it can capture essential aspects of the complex evolutionary dynamics of pathogens such as influenza.

Antigenic Variation↗
PubMed2004

The epidemiology of severe acute respiratory syndrome in the 2003 Hong Kong epidemic: an analysis of all 1755 patients.

BACKGROUND: As yet, no one has written a comprehensive epidemiologic account of a severe acute respiratory syndrome (SARS) outbreak from an affected country. OBJECTIVE: To provide a comprehensive epidemiologic account of a SARS outbreak from an affected territory. DESIGN: Epidemiologic analysis. SETTING: The 2003 Hong Kong SARS outbreak. PARTICIPANTS: All 1755 cases and 302 deaths. MEASUREMENTS: Sociodemographic characteristics; infection clusters by time, occupation, setting, and workplace; and geospatial relationships were determined. The mean and variance in the time from infection to onset (incubation period) were estimated in a small group of patients with known exposure. The mean and variance in time from onset to admission, from admission to discharge, or from admission to death were calculated. Logistic regression was used to identify important predictors of case fatality. RESULTS: 49.3% of patients were infected in clinics, hospitals, or elderly or nursing homes, and the Amoy Gardens cluster accounted for 18.8% of cases. The ratio of women to men among infected individuals was 5:4. Health care workers accounted for 23.1% of all reported cases. The estimated mean incubation period was 4.6 days (95% CI, 3.8 to 5.8 days). Mean time from symptom onset to hospitalization varied between 2 and 8 days, decreasing over the course of the epidemic. Mean time from onset to death was 23.7 days (CI, 22.0 to 25.3 days), and mean time from onset to discharge was 26.5 days (CI, 25.8 to 27.2 days). Increasing age, male sex, atypical presenting symptoms, presence of comorbid conditions, and high lactate dehydrogenase level on admission were associated with a greater risk for death. LIMITATIONS: Estimates of the incubation period relied on statistical assumptions because few patients had known exposure times. Temporal changes in case management as the epidemic progressed, unavailable treatment information, and several potentially important factors that could not be thoroughly analyzed because of the limited sample size complicate interpretation of factors related to case fatality. CONCLUSIONS: This analysis of the complete data on the 2003 SARS epidemic in Hong Kong has revealed key epidemiologic features of the epidemic as it evolved.

Adult↗
PubMed2004

Epidemiology, transmission dynamics and control of SARS: the 2002-2003 epidemic.

This paper reviews current understanding of the epidemiology, transmission dynamics and control of the aetiological agent of severe acute respiratory syndrome (SARS). We present analyses of data on key parameters and distributions and discuss the processes of data capture, analysis and public health policy formulation during the SARS epidemic are discussed. The low transmissibility of the virus, combined with the onset of peak infectiousness following the onset of clinical symptoms of disease, transpired to make simple public health measures, such as isolating patients and quarantining their contacts, very effective in the control of the SARS epidemic. We conclude that we were lucky this time round, but may not be so with the next epidemic outbreak of a novel aetiological agent. We present analyses that help to further understanding of what intervention measures are likely to work best with infectious agents of defined biological and epidemiological properties. These lessons learnt from the SARS experience are presented in an epidemiological and public health context.

Age Factors↗
PubMed2004

Factors that make an infectious disease outbreak controllable.

The aim of this study is to identify general properties of emerging infectious agents that determine the likely success of two simple public health measures in controlling outbreaks, namely (i) isolating symptomatic individuals and (ii) tracing and quarantining their contacts. Because these measures depend on the recognition of specific disease symptoms, we investigate the relative timing of infectiousness and the appearance of symptoms by using a mathematical model. We show that the success of these control measures is determined as much by the proportion of transmission occurring prior to the onset of overt clinical symptoms (or via asymptomatic infection) as the inherent transmissibility of the etiological agent (measured by the reproductive number R(0)). From published studies, we estimate these quantities for two moderately transmissible viruses, severe acute respiratory syndrome coronavirus and HIV, and for two highly transmissible viruses, smallpox and pandemic influenza. We conclude that severe acute respiratory syndrome and smallpox are easier to control using these simple public health measures. Direct estimation of the proportion of asymptomatic and presymptomatic infections is achievable by contact tracing and should be a priority during an outbreak of a novel infectious agent.

Communicable Diseases, Emerging↗
PubMed2004

Epidemiological and genetic analysis of severe acute respiratory syndrome.

The severe acute respiratory syndrome (SARS) epidemics in 2002-2003 showed how quickly a novel infectious disease can spread both within communities and internationally. We have reviewed the epidemiological and genetic analyses that have been published both during and since these epidemics, and show how quickly data were collected and analyses undertaken. Key factors that determine the speed and scale of transmission of an infectious disease were estimated using statistical and mathematical modelling approaches, and phylogenetic analyses provided insights into the origin and evolution of the SARS-associated coronavirus. The SARS literature continues to grow, and it is hoped that international collaboration in the analysis of epidemiological and contact-network databases will provide further insights into the spread of this newly emergent infectious disease.

China↗
PubMed2004

Scale-free networks and sexually transmitted diseases: a description of observed patterns of sexual contacts in Britain and Zimbabwe.

BACKGROUND: Sexually transmitted infections spread through a network of contacts created by the formation of sexual partnerships. In physics, networks have been characterized as "scale-free" if they follow a power law with an exponent between 2 and 3. OBJECTIVE: The objective of this study was to test statistically whether distributions of numbers of sexual partners reported from different populations are well described by power laws. STUDY DESIGN: Power laws and an exponential null model are fitted by maximum likelihood techniques to reported distributions of numbers of partners. Data are taken from 4 population-based surveys, 3 from Britain and 1 from rural Zimbabwe. RESULTS: The networks can be described by power laws over a number of orders of magnitude. In addition, the derived exponents differ significantly and meaningfully, with an "accelerating network" formed between men who have sex with men (MSM). CONCLUSIONS: A scale-free network approach provides a reasonable description of distributions of reported numbers of sexual partners.

Adolescent↗
PubMed2004

SARS-CoV antibody prevalence in all Hong Kong patient contacts.

A total of 1,068 asymptomatic close contacts of patients with severe acute respiratory (SARS) from the 2003 epidemic in Hong Kong were serologically tested, and 2 (0.19%) were positive for SARS coronavirus immunoglobulin G antibody. SARS rarely manifests as a subclinical infection, and at present, wild animal species are the only important natural reservoirs of the virus.

Adolescent↗
PubMed2003

Robust parameter estimation techniques for stochastic within-host macroparasite models.

We present a stochastic model of the within-host population dynamics of lymphatic filariasis, and use a simulated goodness-of-fit (GOF) method to estimate immunological parameters and their confidence intervals from experimental data. A variety of deterministic moment closure approximations to the stochastic system are explored and compared with simulation results. For the maximum GOF parameter estimates, none of the methods of closure accurately reproduce the behaviour of the stochastic model. However, direct analysis of the stochastic model demonstrates that the high levels of variation observed in the data can be reproduced without requiring parameters to vary between hosts. This indicates that the observed aggregation of parasite load may be dynamically generated by random variation in the development of an effective immune response against parasite larvae.

Animals↗
PubMed2003

Planning for smallpox outbreaks.

Mathematical models of viral transmission and control are important tools for assessing the threat posed by deliberate release of the smallpox virus and the best means of containing an outbreak. Models must balance biological realism against limitations of knowledge, and uncertainties need to be accurately communicated to policy-makers. Smallpox poses the particular challenge that key biological, social and spatial factors affecting disease spread in contemporary populations must be elucidated largely from historical studies undertaken before disease eradication in 1979. We review the use of models in smallpox planning within the broader epidemiological context set by recent outbreaks of both novel and re-emerging pathogens.

Bioterrorism↗
PubMed2003

Assessment of the risk posed by bovine spongiform encephalopathy in cattle in Great Britain and the impact of potential changes to current control measures.

We extended an existing back-calculation model to analyse data on reported clinical cases of bovine spongiform encephalopathy (BSE), data from random testing of healthy animals slaughtered in abattoirs and testing data from animals reported as sick or dying on the farm. Extensive analysis of demographic data was also undertaken. We estimated past and current BSE infection prevalences in the cattle population and the degree of case under-ascertainment resulting from excess mortality in cattle near to disease onset. Ongoing levels of human exposure to BSE infectivity were also estimated, together with the effect on these of a range of possible exposure-reduction strategies that might replace the current rule banning tissue from cattle over 30 months (OTM) of age from the human food supply. While any policy change that allows a wider age range of animals into the human food supply will increase levels of human exposure to infectivity, the risk posed by such increases is small by comparison with historical exposure levels. Making the pessimistic assumption that there will be 5000 deaths during the variant Creutzfeldt-Jakob disease (vCJD) epidemic in total, our analysis indicates that replacement of the OTM rule with testing would result in 0.04 additional vCJD deaths over the next 60 years. However, there is substantial (more than 40-fold) uncertainty surrounding this estimate, the sources of which are discussed.

Animals↗
PubMed2003

Epidemiological determinants of spread of causal agent of severe acute respiratory syndrome in Hong Kong.

BACKGROUND: Health authorities worldwide, especially in the Asia Pacific region, are seeking effective public-health interventions in the continuing epidemic of severe acute respiratory syndrome (SARS). We assessed the epidemiology of SARS in Hong Kong. METHODS: We included 1425 cases reported up to April 28, 2003. An integrated database was constructed from several sources containing information on epidemiological, demographic, and clinical variables. We estimated the key epidemiological distributions: infection to onset, onset to admission, admission to death, and admission to discharge. We measured associations between the estimated case fatality rate and patients' age and the time from onset to admission. FINDINGS: After the initial phase of exponential growth, the rate of confirmed cases fell to less than 20 per day by April 28. Public-health interventions included encouragement to report to hospital rapidly after the onset of clinical symptoms, contact tracing for confirmed and suspected cases, and quarantining, monitoring, and restricting the travel of contacts. The mean incubation period of the disease is estimated to be 6.4 days (95% CI 5.2-7.7). The mean time from onset of clinical symptoms to admission to hospital varied between 3 and 5 days, with longer times earlier in the epidemic. The estimated case fatality rate was 13.2% (9.8-16.8) for patients younger than 60 years and 43.3% (35.2-52.4) for patients aged 60 years or older assuming a parametric gamma distribution. A non-parametric method yielded estimates of 6.8% (4.0-9.6) and 55.0% (45.3-64.7), respectively. Case clusters have played an important part in the course of the epidemic. INTERPRETATION: Patients' age was strongly associated with outcome. The time between onset of symptoms and admission to hospital did not alter outcome, but shorter intervals will be important to the wider population by restricting the infectious period before patients are placed in quarantine.

Adolescent↗
PubMed2003

Transmission dynamics of the etiological agent of SARS in Hong Kong: impact of public health interventions.

We present an analysis of the first 10 weeks of the severe acute respiratory syndrome (SARS) epidemic in Hong Kong. The epidemic to date has been characterized by two large clusters-initiated by two separate "super-spread" events (SSEs)-and by ongoing community transmission. By fitting a stochastic model to data on 1512 cases, including these clusters, we show that the etiological agent of SARS is moderately transmissible. Excluding SSEs, we estimate that 2.7 secondary infections were generated per case on average at the start of the epidemic, with a substantial contribution from hospital transmission. Transmission rates fell during the epidemic, primarily as a result of reductions in population contact rates and improved hospital infection control, but also because of more rapid hospital attendance by symptomatic individuals. As a result, the epidemic is now in decline, although continued vigilance is necessary for this to be maintained. Restrictions on longer range population movement are shown to be a potentially useful additional control measure in some contexts. We estimate that most currently infected persons are now hospitalized, which highlights the importance of control of nosocomial transmission.

Cluster Analysis↗
PubMed2003

Updated projections of future vCJD deaths in the UK.

BACKGROUND: Past projections of the future course of the vCJD epidemic in the UK have shown considerable uncertainty, with wide confidence bounds. However, recent vCJD case data have indicated a decrease in the annual incidence of deaths over the past two years. METHODS: A detailed survival model is fitted to the 121 vCJD deaths reported by the end of 2002 stratified by age and calendar time to obtain projections of future incidence. The model is additionally fitted to recent results from a survey of appendix tissues. RESULTS: Our results show a substantial decrease in the uncertainty of the future course of the primary epidemic in the susceptible genotype (MM-homozygous at codon 129 of the prion protein gene), with a best estimate of 40 future deaths (95% prediction interval 9-540) based on fitting to the vCJD case data alone. Additional fitting of the appendix data increases these estimates (best estimate 100, 95% prediction interval 10-2,600) but remains lower than previous projections. CONCLUSIONS: The primary vCJD epidemic in the known susceptible genotype in the UK appears to be in decline.

Creutzfeldt-Jakob Syndrome↗
PubMed2003

Factors determining the pattern of the variant Creutzfeldt-Jakob disease (vCJD) epidemic in the UK.

Following the emergence of a new variant of Creutzfeldt-Jakob disease (vCJD) 6 years ago, and the gradual rise in clinical cases, there has been increased speculation regarding the overall magnitude of this epidemic in Great Britain. In this paper, we explore the epidemiological factors and uncertainties determining the scale of this epidemic in light of the most recent data on reported vCJD mortality. Our results demonstrate that, while the magnitude of the uncertainty has decreased dramatically since 1996, it is still not possible to predict with any degree of accuracy the final magnitude of this epidemic, with the 95% confidence interval for future cases being from 10 to 7000 deaths. However, short-term projections show that it is unlikely that a dramatic increase in case numbers will be observed in the next 2-5 years (95% confidence interval for 2 years: 10-80 cases, for 5 years: 10-200 cases). The results confirm significant age-dependent susceptibility/exposure to infection, with the likelihood profile demonstrating that those aged between 10 and 20 years are at highest risk of infection. We also demonstrate how projections based on onset data may be substantially biased, and explore the sensitivity of results to assumptions concerning the exposure to bovine spongiform encephalopathy (BSE) and the incubation-period distribution.

Age Factors↗