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Biomedical subjects

R M Anderson

Publications and source records attributed to R M Anderson.

At least 73 records · Page 4Linked to original sources
PubMed1999

Transmission dynamics of epidemic methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci in England and Wales.

A simple epidemiological framework for the analysis of the transmission dynamics of hospital outbreaks of epidemic methicillin-resistant Staphylococcus aureus (EMRSA) and vancomycin-resistant enterococci (VRE) in hospitals in England and Wales is presented. Epidemic strains EMRSA-15 and EMRSA-16 are becoming endemic in hospitals in the United Kingdom, and theory predicts that EMRSA-15 and EMRSA-16 will reach respective endemic levels of 158 (95% confidence interval [CI], 143-173) and 116 (95% CI, 109-123) affected hospitals with stochastic fluctuations of up to 30 hospitals in each case. An epidemic of VRE is still at an early stage, and the incidence of hospitals newly affected by VRE is growing exponentially at a rate r=0.51/year (95% CI, 0.48-0.54). The likely impact of introducing surveillance policies if action is taken sufficiently early is estimated. Finally, the role of heterogeneity in hospital size is considered: "Super-spreader hospitals" may increase transmission by 40%-132% above the expected mean.

Cross Infection↗
PubMed1999

A second operator is involved in Pseudomonas aeruginosa elastase (lasB) activation.

Pseudomonas aeruginosa LasB elastase gene (lasB) transcription is controlled by the two-component quorum-sensing system of LasR, and the autoinducer, 3OC(12)-HSL (N-3-[oxododecanoyl]homoserine lactone). LasR and 3OC(12)-HSL-mediated lasB activation requires a functional operator sequence (OP1) in the lasB promoter region. Optimal activation of lasB, however, requires a second sequence of 70% identity to OP1, named OP2, located 43 bp upstream of OP1. In this study, we used sequence substitutions and insertion mutations in lasBp-lacZ fusion plasmids to explore the role of OP2 in lasB activation. Our results demonstrate that (i) OP1 and OP2 synergistically mediate lasB activation; (ii) OP2, like OP1, responds to LasR and 3OC(12)-HSL; and (iii) the putative autoinducer-binding domain of LasR is not required for synergistic activation from OP1 and OP2.

Bacterial Proteins↗
PubMed1999

Sexual mixing patterns in the spread of gonococcal and chlamydial infections.

OBJECTIVES: This study sought to define, among sexually transmitted disease (STD) clinic attendees, (1) patterns of sex partner selection, (2) relative risks for gonococcal or chlamydial infection associated with each mixing pattern, and (3) selected links and potential and actual bridge populations. METHODS: Mixing matrices were computed based on characteristics of the study participants and their partners. Risk of infection was determined in study participants with various types of partners, and odds ratios were used to estimate relative risk of infection for discordant vs concordant partnerships. RESULTS: Partnerships discordant in terms of race/ethnicity, age, education, and number of partners were associated with significant risk for gonorrhea and chlamydial infection. In low-prevalence subpopulations, within-subpopulation mixing was associated with chlamydial infection, and direct links with high-prevalence subpopulations were associated with gonorrhea. CONCLUSIONS: Mixing patterns influence the risk of specific infections, and they should be included in risk assessments for individuals and in the design of screening, health education, and partner notification strategies for populations.

Adolescent↗
PubMed1998

Epidemiological determinants of the pattern and magnitude of the vCJD epidemic in Great Britain.

Understanding the epidemiology and aetiology of new-variant Creutzfeldt-Jakob (vCJD) disease in humans has become increasingly important given the scientific evidence linking it to bovine spongiform encephalopathy (BSE) in cattle and hence the wide exposure of the population of Great Britain (GB) to potentially infectious tissue. The recent analysis undertaken to determine the risk to the population from dorsal route ganglia illustrated the danger in presenting point estimates rather than ranges of scenarios in the face of uncertainty. We present a mathematical template that relates the past pattern of the BSE epidemic in cattle to the future course of any vCJD epidemic in humans, and use extensive scenario analysis to explore the wide range of possible outcomes given the uncertainty in epidemiological determinants. We demonstrate that the average number of humans infected by one infectious bovine and the incubation period distribution are the two epidemiological factors that have the greatest impact on epidemic size and duration. Using the time-series of the BSE epidemic and the cases seen to date, we show that the minimum length of the incubation period is approximately nine years, and that at least 20% of the cases diagnosed to date were exposed prior to 1986. We also demonstrate that the current age distribution of vCJD cases can only arise if younger people were either exposed to a greater extent, more susceptible to infection, or have shorter incubation periods. Extensive scenario analyses show that given the information currently available, the very high degree of uncertainty in the future size of the epidemic will remain for the next 3-5 years. Furthermore, we demonstrate that this uncertainty is unlikely to be reduced by mass screening for late-stage infection.

Creutzfeldt-Jakob Syndrome↗
PubMed1998

Estimating HIV incidence from age-specific prevalence data: comparison with concurrent cohort estimates in a study of male factory workers, Harare, Zimbabwe.

OBJECTIVE: To compare HIV incidence estimates from cross-sectional age-specific prevalence data with concurrent cohort estimates and to examine the sensitivity of the estimates to changes in age-categorization and survivorship assumptions. METHODS: Two previously described methods of estimating HIV incidence from cross-sectional prevalence data - the cumulative incidence and survival (CIS) and constant prevalence (CP) methods - are applied using data from a study of male factory workers in Harare, Zimbabwe. The methods are applied under two alternative groupings of the HIV prevalence data and under alternative survivorship assumptions: (a) Weibull distribution providing the best fit to the HIV prevalence data using the CIS method; (b) Weibull distribution matching data from an HIV natural history cohort study in Uganda; and (c) survivorship pattern as in (b) with survival periods reducing with increasing age at infection. Age-specific, age-standardized and cumulative HIV incidence estimates are calculated. The results are compared with concurrent longitudinal estimates from 3 years of follow-up of the Harare cohort (1993-1995). RESULTS: Age-standardized HIV incidence was estimated at 2.02 per 100 man years (95% CI, 1.57-2.47) in the cohort study. There was evidence of recent variability in HIV incidence in these data. Estimates from the cross-sectional methods ranged from 1.98 to 2.74 per 100 man years and were sensitive to changes in age-categorization of the HIV prevalence data and changes in survivorship assumptions. The cross-sectional estimates were higher at central ages and lower at older ages than the cohort estimates. The age-specific estimates from the CIS method were less sensitive to changes in age grouping than those from the CP method. CONCLUSIONS: HIV incidence remains high in Harare. Incidence estimates broadly consistent with cohort estimates can be obtained from single-round cross-sectional HIV prevalence data in established epidemics - even when the underlying assumption of stable endemic prevalence is not fully met. Estimates based on cross-sectional surveys should therefore be explored when reliable longitudinal estimates cannot be obtained. More data on post-HIV infection survivorship distributions in sub-Saharan Africa would facilitate the improvement of estimates of incidence based on cross-sectional surveys.

Adolescent↗
PubMed1998

The dynamics of drug action on the within-host population growth of infectious agents: melding pharmacokinetics with pathogen population dynamics.

The use of simple mathematical models to study the kinetics of drug action and decay within vertebrate hosts has a long history with a major objective being to derive drug dosage regimens that optimize efficacy and minimize toxicity to the patient. Mathematical models of the relationship between dosage, route of delivery, drug concentration in defined sites and effect on a particular pathogen are widely used in the pharmacological literature. A more recent literature is that concerned with the population dynamics of pathogen replication within the host subjected to pressures exerted by the human immune system. In this paper we develop a theoretical framework to meld both approaches with the aim of identifying threshold criteria that dictate the optimum pattern of drug administration for pathogen clearance from the host. In particular we show how the percentage reduction in microparasite abundance is related to the pharmacokinetic parameter, AUC, recording the area under the drug concentration-time curve within the treated patient, in terms of the parameters that define the population dynamics of the pathogen and the properties of the drug. Two particular pathogens are examined to illustrate the principles underpinning the dynamics of the pharmacokinetic-population dynamic models, namely HIV and Plasmodium falciparum. Criteria for pathogen persistence or elimination are derived for these specific models based on the definition of a basic reproductive number, R0, which measures the average number of secondary infected target cells in a host generated by a single infected cell (CD4 lymphocyte for HIV, and erythrocyte for P. falciparum) within a population of susceptible cells. For the pathogen to invade the host and persist over time, R0</=1. Under chemotherapeutic regimens, expressions for R0 are derived allowing estimates to be made of the ideal treatment regime required to eliminate the pathogen, both for HIV and P. falciparum malaria.

Animals↗
PubMed1998

Epidemiology and control of scrapie within a sheep flock.

Mathematical models of the transmission dynamics of scrapie are used to explore the expected course of an outbreak in a sheep flock, and the potential impacts of different control measures. All models incorporate sheep demography, a long and variable scrapie incubation period, horizontal and vertical routes of transmission and genetic variation in susceptibility. Outputs are compared for models which do and do not incorporate an environmental reservoir of infectivity, and which do and do not incorporate carrier genotypes. Numerical analyses using parameter values consistent with available data indicate that, in a closed flock, scrapie outbreaks may have a duration of several decades, reduce the frequency of susceptible genotypes, and may become endemic if carrier genotypes are present. In an open flock, endemic scrapie is possible even in the absence of carriers. Control measures currently or likely to become available may reduce the incidence of cases but may be fully effective only over a period of several years.

Animals↗
PubMed1998

Rabies in Zimbabwe: reservoir dogs and the implications for disease control.

Using detailed field study observations of the side-striped jackal (Canis adustus) and a simple stochastic model of the transmission dynamics of the virus and host demography, we discuss the epidemiology of rabies virus infection in the jackal population of Zimbabwe. Of the two jackal species in Zimbabwe, the other being the black-backed jackal (Canis mesomelas), the bulk of notified rabies cases are in side-striped jackals. Specifically, we show that the side-striped jackal population itself does not seem able to support rabies infection endemically, i.e. without frequent reintroduction from outside sources of infection. We argue that this is probably because the overall average jackal population density is too low to maintain the chain of infection. This study suggests that the disease is regularly introduced to jackals by rabid dogs from populations associated with human settlements. Given the rapidly rising dog population in Zimbabwe, estimates are derived of the future incidence of jackal rabies based on different dog-vaccination scenarios.

Animals↗
PubMed1998

Demographic impact of the HIV epidemic in Thailand.

OBJECTIVE: To assess the impact of the HIV epidemic on the demographic development of the Thai population. METHODS: A deterministic mathematical model was used to predict simultaneously epidemiological and demographic processes. Partial differential equations express the relationships between biological, behavioural and demographic variables. The model allows the evaluation of different sexual mixing patterns, variable transmission probabilities and incubation times. Validity analysis was performed by generating antecedent HIV prevalence patterns among military recruits and pregnant women. RESULTS: On the national level in Thailand we predict that the cumulative number of people in Thailand with HIV infection will exceed 1 million by 1999; the number of deaths from AIDS will be 555000 by the year 2000 but will not reach 1 million until after the year 2014. Without the HIV epidemic the population growth rate was estimated at 1.3% per annum until 1995, after which a decline to 0.9% by 2005 is predicted. The HIV epidemic started to affect the population growth rate by 0.026% per year in 1991, and the difference is predicted to rise to about 0.12% per year during the period 1995-2000, to decline to 0.06% in 2005 and then to disappear. In the mid-1990s HIV affected mainly the 15-35-year-old age group, but over time younger and older age groups have been affected as a result of perinatal transmission, and a decline in fertility as well as ageing of the 15-35-year-old birth cohort. Because of HIV, in 2000 there will be 612000 (1%) fewer people than expected and by 2010, 1140000 fewer (1.6%). We predict that the demographic impact of the HIV epidemic in the northern region will follow the same pattern, but with greater severity. Here, the effect on the population growth rate and the population age distribution is likely to be twice as high as at the national level. CONCLUSIONS: It is estimated that 1 million Thais will be infected with HIV by the year 2000 and an almost equal number will have died of AIDS by the year 2014. Although these numbers seem high, their direct and indirect effects on the demographic structure of the Thai population are small. However, at a regional level, for example in the northern region, the effect of the HIV epidemic may be more severe.

Acquired Immunodeficiency Syndrome↗
PubMed1998

BSE in Northern Ireland: epidemiological patterns past, present and future.

By 30 January 1998, there had been 170,259 confirmed cases of BSE in Great Britain (GB), 1766 confirmed cases in Northern Ireland (NI) (2 January 1998), and 276 confirmed cases in the Republic of Ireland (31 January 1998). Analysis of the epidemiological patterns in the NI epidemic reveals significant clustering of cases in herds and counties. The observed clustering of cases within herds results in lower per capita incidence of BSE in previously unaffected herds, providing support for the introduction of a certified herd scheme in NI. By fitting a backcalculation model to the case data, we can estimate the number of animals infected with the aetiological agent of BSE and project the number of future cases. We predict that the epidemic will decline rapidly, with approximately 99 cases (95% confidence interval 30,504) occurring in the five year period 1997-2001.

Animals↗
PubMed1998

Epidemiology of communicable disease in small populations.

We have recently shown how the outbreaks of measles virus infection in small isolated island communities exhibit an organised pattern in the distribution of epidemic sizes and distribution of epidemic durations. More conventional epidemiological analysis tends not to be useful in such highly intermittent dynamical regimes where there is frequent fade-out of infection. In this paper we discuss how our approach can be applied to an analysis of measles epidemics in highly vaccinated communities where susceptibles build up due to lack of vaccine uptake and also because of occasional vaccine failure.

Communicable Diseases↗
PubMed1998

Complex dynamic behaviours in the interaction between parasite population and the host's immune system.

The paper describes recent progress in the development of a mathematical framework for the study of epidemiology, evolution, within-host parasite population growth and the control of parasitic infections. A major emphasis is placed on dynamic models of the interaction between the parasite population and the host's immune system that capture the effects of antigenic variation, parasite evolution in response of immunological attack and the control of population growth by chemotherapeutic agents.

Animals↗
PubMed1998

Is there evidence for behaviour change in response to AIDS in rural Zimbabwe?

This article reports on evidence for behaviour change in response to AIDS among women in two rural areas of Manicaland Province, Zimbabwe. It examines self-reported data on two overlapping areas of behaviour: (1) actions taken to avoid HIV-1 infection; and (2) fertility practices. The latter were used to assess the validity of the former, given that self-reported behaviour data are notoriously problematic. It is concluded that while self-reported behaviour change is exaggerated, the true level of change has nonetheless been significant and includes delayed onset of sexual relations, increased use of condoms and, possibly, increased monogamy. Reported actions taken to avoid HIV-1 infection and differentials in fertility practices were correlated with data on demographic, social and psychological factors. Differentials in fertility practices were associated with heightened risk perception--particularly when based on personal acquaintance with AIDS patients--but not with greater knowledge of HIV-1/AIDS. Results from the study suggest that effective behaviour change in Manicaland is facilitated by greater knowledge, experience and personal risk perception but obstructed by low female autonomy, marital status and economic status, and by male labour migration and alcohol consumption. Gaps in knowledge included misconceptions about the distinction between HIV-1 and AIDS, the influence of STDs, perinatal transmission, and incorrect modes of transmission. Better knowledge was associated with education, religion, travel and media exposure Personal risk perception was quite high (42%) and correlated with non-marriage, media exposure and contact with medical services. Few respondents knew close relatives with HIV/AIDS (4%) but nearly a quarter of those who felt in danger of infection said this was because friends and relatives were dying of AIDS. Many reported credible behavioural responses, some of which would only be effective given their partner's co-operation. Intensified behaviour interventions are needed which should include peer-education initiatives targeting men and individuals without access to modern media. The epidemic may accelerate fertility decline in rural Zimbabwe through behavioural as well as biological change.

Adolescent↗
PubMed1998

Absence of relationship between Schistosoma japonicum and hepatitis B virus infection in the Dongting lake region, China.

In order to determine whether infection with Schistosoma japonicum is related to a higher rate of infection with hepatitis B virus and/or to a higher probability of HBsAg chronic carriage, a population based survey was carried out in China in which HBV markers were studied in 112 subjects with long-lasting S. japonicum infection, and 93 subjects with no S. japonicum infection 37.5% of the cases and 40.9% of controls showed no markers of HBV infection. The prevalence rate of HBsAg was 12.5% in the cases and 12.9% in the controls. For anti-HBc and anti-HBs the figures were 59.8% and 59.8%, and 27.9% and 35.0%, respectively. These data do not support the hypothesis of an interaction between infection with hepatitis B virus and S. japonicum.

Adolescent↗