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Roy M Anderson

Publications and source records attributed to Roy M Anderson.

14 recordsLinked to original sources
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↗
PubMed2003

Short-term projections for variant Creutzfeldt-Jakob disease onsets.

Projections of both the short- and long-term course of the variant Creutzfeldt-Jakob disease (vCJD) epidemic in Great Britain have demonstrated great uncertainty due to the lack of knowledge of key aspects of the biology and epidemiology of this new disease. Such projections are sensitive to assumptions made regarding the pattern of exposure to BSE-infected animals, the effectiveness of control measures introduced in 1989 and 1996 in reducing this exposure, the functional form of the incubation period distribution and patterns of age-dependent susceptibility/exposure. This paper provides short-term projections for vCJD onsets using the time- and age-distributed onset data to the end of 2000, with results that are directly comparable to the other papers in this issue. These results demonstrate the continued uncertainty in the future scale of this disease.

Age Distribution↗
PubMed2002

Antigen-driven T-cell turnover.

A mathematical model is developed to characterize the distribution of cell turnover rates within a population of T lymphocytes. Previous models of T-cell dynamics have assumed a constant uniform turnover rate; here we consider turnover in a cell pool subject to clonal proliferation in response to diverse and repeated antigenic stimulation. A basic framework is defined for T-cell proliferation in response to antigen, which explicitly describes the cell cycle during antigenic stimulation and subsequent cell division. The distribution of T-cell turnover rates is then calculated based on the history of random exposures to antigens. This distribution is found to be bimodal, with peaks in cell frequencies in the slow turnover (quiescent) and rapid turnover (activated) states. This distribution can be used to calculate the overall turnover for the cell pool, as well as individual contributions to turnover from quiescent and activated cells. The impact of heterogeneous turnover on the dynamics of CD4(+) T-cell infection by HIV is explored. We show that our model can resolve the paradox of high levels of viral replication occurring while only a small fraction of cells are infected.

Antigens, Viral↗
PubMed2002

Implications of BSE infection screening data for the scale of the British BSE epidemic and current European infection levels.

The incidence of confirmed clinical cases of bovine spongiform encephalopathy (BSE) in Great Britain continues to decline, but the recent discovery of cases in previously unaffected countries (including Israel, Japan, Poland, Slovenia and Spain) has heightened concerns that BSE transmission was more intense and widespread than previously thought. We use back-calculation methods to undertake an integrated analysis of data on infection prevalence in apparently healthy cattle and the incidence of confirmed clinical disease. The results indicate substantial underascertainment of clinical cases over the course of the British epidemic, and consequently that two- to fourfold more animals were infected than previously estimated. Upper bounds on the predicted size of the new variant Creutzfeldt-Jakob Disease (vCJD) epidemic are unaffected, as the prediction methods employed fit to observed vCJD mortality data, and are not sensitive to estimates of the absolute magnitude of past human exposure to BSE-infected cattle, only to relative changes in exposure through time. We also estimate the per-head incidence of infection in cattle born between 1993 and 1997 in other European Union countries, using data on the testing of apparently healthy cattle slaughtered for consumption. Infection incidence for cattle born after mid-1996 was highest in Greece, Italy and Belgium, with Spain and The Netherlands having intermediate levels, and estimates for Great Britain, Germany and France being comparably low.

Animals↗
PubMed2002

Can we reverse the HIV/AIDS pandemic with an expanded response?

HIV/AIDS has reached pandemic proportions, and is one of the leading causes of death worldwide. In 2001, the Declaration of Commitment on HIV/AIDS set out several aims with respect to reducing the effect and spread of HIV/AIDS, and an expanded response in low-income and middle-income countries was initiated. Here we examine the potential effect of the expanded global response based on analyses of epidemiological data, of mathematical models of HIV-1 transmission, and a review of the impact of prevention interventions on risk behaviours. Analyses suggest that if the successes achieved in some countries in prevention of transmission can be expanded to a global scale by 2005, about 29 million new infections could be prevented by 2010.

Acquired Immunodeficiency Syndrome↗
PubMed2002

Sexual mixing patterns and sex-differentials in teenage exposure to HIV infection in rural Zimbabwe.

BACKGROUND: HIV-1 prevalence typically rises more rapidly at young ages in women than in men in sub-Saharan Africa. Greater susceptibility to infection on exposure in women is believed to be a contributory factor as is greater exposure to previously infected sexual partners of the opposite sex. We investigated the latter hypothesis using data from a field study in rural Manicaland, Zimbabwe. METHODS: Quantitative data on onset and degree of sexual activity, numbers of partners, concurrent partnerships, condom use, and partner characteristics were used in conjunction with epidemiological data on age and sex specific prevalence of HIV infection to do statistical analyses of association between key variables. Mathematical models and qualitative data were used to aid analysis and interpretation. FINDINGS: Older age of sexual partner was associated with increased risk of HIV-1 infection in men (odds ratio 1.13 [95% CI 1.02-1.25]) and women (1.04 [1.01-1.07]). Young women form partnerships with men 5-10 years older than themselves, whereas young men have relationships with women of a similar age or slightly younger. Greater number of lifetime partners is also associated with increased risk of HIV (1.03 [1.00-1.05]). Young men report more partners than do women but infrequent coital acts and greater use of condoms. These behaviour patterns are underpinned by cultural factors including the expectation that women should marry earlier than men. A strong gender effect remains after factors that affect exposure to infected partners are controlled for (6.04 [1.49-24.47]). INTERPRETATION: The substantial age difference between female and male sexual partners in Manicaland is the major behavioural determinant of the more rapid rise in HIV prevalence in young women than in men. Theoretical studies have suggested that this difference is an important determinant of observed epidemiological patterns but the study reported in this paper provides clear empirical evidence of association.

Adolescent↗
PubMed2002

Viral replication under combination antiretroviral therapy: a comparison of four different regimens.

A mathematical model of the interaction among CD4+ T-cells, HIV-1, and antiretroviral drugs was fitted to the viral load decline following initiation of combination therapy to estimate differences in the residual reproductive capacity of virus (R(0)) in the average patient in each group. Four regimens were studied: 12 patients on 5-drug nucleoside reverse transcriptase inhibitor (NRTIs), nonnucleoside reverse transcriptase inhibitor (NNRTIs) and protease inhibitor (PI)-containing combination therapy, 11 patients on PI-containing triple therapy, 10 patients on double NRTI therapy, and 10 patients on NNRTI-containing triple therapy. Model fits were used to estimate R(0). The NNRTI-containing triple therapy and the 5-drug regimen blocked viral replication to the greatest extent (R(0) = 0.85; 95% confidence interval [CI], 0.79-0.91; and 0.90, 95% CI, 0.82-0.98, respectively), with the former being significantly better than the PI-containing triple regimen (R(0) = 0.98; 95% CI, 0.92-1.03; p =.007). Both the NNRTI-containing and the 5-drug regimen, as well as the PI-containing triple therapy, were significantly better at blocking viral replication than the double NRTI therapy (R(0) = 1.04; 95% CI, 1.0-1.07). Measurement of viral load after approximately 7 days provided the most accurate measure of the degree of viral suppression induced by a given drug regimen.

Adult↗
PubMed2002

Study of bias in antenatal clinic HIV-1 surveillance data in a high contraceptive prevalence population in sub-Saharan Africa.

OBJECTIVE: To describe patterns, sources and consequences of bias in antenatal clinic (ANC) HIV prevalence estimates in a high contraceptive prevalence population. BACKGROUND: HIV surveillance in Africa relies on data from pregnant women attending ANCs. HIV estimates from pregnant women understate female infection levels in low income, high fertility populations. Bias in high contraceptive use, delayed sexual debut populations remains undescribed. DESIGN AND METHOD: Comparison of parallel cross-sectional population and antenatal survey data from rural Zimbabwe, where 60% of women are recent contraceptive users. RESULTS: HIV prevalence in recently pregnant women (25.7%; n = 576) and all women (25.5%; n = 5138) is similar over the age-range 15-44 years. As in high fertility populations, HIV prevalence is higher in pregnant women at young ages and lower at older ages but the crossover point occurs later due to delayed sexual activity. HIV understatement at older ages due to HIV-associated infertility is mitigated by less HIV infection and less frequent ANC attendance in contraceptive users. The local ANC HIV prevalence estimate is lower [21.2%; n = 1215; risk ratio versus pregnant women in the general population, 0.8; 95% confidence interval (CI), 0.7-1.0], possibly because women from more remote areas are included. ANC estimates overstate the relative risk of HIV in more educated women (age-adjusted odds ratio, 1.1; 95% CI, 0.8-1.4 versus 0.7; 95% CI, 0.6-0.9). CONCLUSIONS: ANC estimates understate female HIV prevalence in this low fertility population but, here, the primary cause is not selection of pregnant women. ANC estimate adjustment procedures that control for contraceptive use and age at first sex are needed.

Adolescent↗
PubMed2002

The transmission dynamics of BSE and vCJD.

The bovine spongiform encephalopathy (BSE) epidemic in cattle has had a huge economic impact on the agricultural industries across Europe. Furthermore, scientific evidence now strongly supporting a link between a new variant of Creutzfeldt-Jakob disease (vCJD) and consumption of BSE-infected animals has further heightened the need both to understand the transmission of these new diseases and to improve control measures to protect public health. In this paper we review work undertaken by our group using epidemiological models to understand the transmission dynamics of BSE and vCJD. We present new estimates of the future number of cases of BSE and the number of infected animals slaughtered for consumption for Great Britain, and summarise similar analyses undertaken for Northern Ireland, Ireland, Portugal and France. We also consider the epidemiological determinants of the future course of the vCJD epidemic, including the age and genetic characteristics of the confirmed cases, and present predictions of future case numbers.

Age Factors↗