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D J Nokes

Publications and source records attributed to D J Nokes.

At least 55 records · Page 3Linked to original sources
PubMed1995

Towards eradication of measles virus: global progress and strategy evaluation.

Despite an increase in global measles vaccine coverage from under 20% in 1980 to around 80% in 1990, measles remains a major cause of morbidity and mortality world-wide. This paper addresses a number of issues relating to efforts to control measles, namely, (i) at the global level, how might we assess the impact of measles vaccination on the incidence of infection and associated disease, and, (ii), at the strategic level, how can we utilise an understanding of the transmission dynamics of childhood viral infections to aid the design of optimal immunisation programmes? Based on WHO vaccine coverage data, and organising countries according to similarities in demographic and epidemiological parameters, an age-structured model of measles transmission is used to capture the non-linear dynamics of infection and mass vaccination and to generate projections of the impact of measles immunization world-wide. The results provide a crude indication of the percentage reduction in measles cases by year 2000 (compared with no immunization) and suggest an approximately 70% reduction in cases over all ages, and 77% reduction in cases under 5 years (where there is the greatest risk of case fatality); these suggest that WHO targets for 1995 are unlikely to be achieved. In the second part of the paper, examples are given to illustrate the usefulness of a modelling approach in evaluating measles immunization policy. The introduction of MMR vaccine in the UK in 1988 has resulted in measles incidence falling to an all time low and attention has turned to the requirements of elimination. A realistic age structured model, validated using extensive serological data, is used to compare the merits of single or two dose strategies. Based upon recent estimates of vaccine efficacy (90%) and coverage (92% by end of second year of life) it is suggested that a two-dose policy with a pre-school second dose given irrespective of vaccine history is required to prevent the build up of susceptibles to epidemic proportions in the longer term. In a second example, prompted by the success of the campaign approach to polio and measles elimination in Central and South America, simple models are used to explore and quantify the process by which pulse vaccination programmes (i.e. repeated application across a wide age range) act to control transmission.

England↗
PubMed1995

Predicting the impact of measles vaccination in England and Wales: model validation and analysis of policy options.

Measles incidence in England and Wales has fallen to an all-time low. Attention is now focused on preventing local outbreaks, and, in the long run, on the elimination of indigenous measles. A realistic age-structured (RAS) mathematical model of measles transmission is used to reconstruct the impact of measles vaccination in England and Wales from 1968 to the present and to evaluate the merits of future policy options. In general, the predictions of the model show good agreement with long-term age stratified case reports and seroprevalence surveys. The model underestimates the proportion of cases that are notified in 0-2-year-old children. However, recent work suggests a high degree of misdiagnosis in this age group. Projections on the basis of the existing vaccination strategy in the UK suggest that the present level of measles vaccine coverage will be insufficient to eliminate small seasonal outbreaks of measles. This result is, however, sensitive to the assumed level of vaccine efficacy. Explorations of a variety of changes to current vaccination strategy favour a 2-dose schedule with the second dose administered at age 4 years irrespective of vaccination history. A vaccination campaign in school-age children, to reduce deficits in herd immunity, would accelerate progress towards measles elimination.

Adolescent↗
PubMed1995

The control of childhood viral infections by pulse vaccination.

Pulse vaccination, the repeated application of vaccine over a defined age range, is gaining prominence as a strategy for the elimination of childhood viral infections such as measles and polio. However, unlike routine or continuous mass infant immunization, epidemiological understanding of this control method is in its infancy. This paper develops initial work by Agur et al. (1993) using simple steady-state and age-structured dynamic models to extend the theory of the mechanism of action of pulse vaccination, and to explore the relationship between the maximum permitted interval between pulses and key epidemiological, demographic and vaccination variables. Initially, a conceptual model is presented to illustrate the principles of pulse vaccination and to make comparison with routine immunization procedures. An ordinary differential equation model, which assumes homogeneous mixing, is then used to derive equilibrium expressions for the pulse interval in relation to (i) different demographic profiles, (ii) population growth characteristics (stationary or exponentially increasing), (iii) combined routine and pulse immunization, and (iv) the age range vaccinated. Finally, simulations using age-structured compartmental deterministic models illustrate complex epidemiological dynamics associated with pulse vaccination, particularly where there is age heterogeneity in contact rates in the population. The resultant uncertainty in defining an optimal pulse interval raises concerns of a practical nature.

Age Factors↗
PubMed1994

Rubella seroepidemiology in a non-immunized population of São Paulo State, Brazil.

A rubella serological survey of 476 individuals selected by cluster sampling technique from Caieiras, a small town located in the outskirts of São Paulo city, southeastern Brazil, was carried out over the period November 1990-January 1991. The aim of the study was to characterize rubella epidemiology in a representative non-immunized community in south east Brazil. The survey comprised a seroprevalence study, stratified by age (0-40 years) and a seroconversion study of rubella vaccine in non-infected children below 2 years of age. Mathematical techniques were applied to resultant data sets to determine the age dependent rates of decay in the proportion of individuals with maternally derived antibodies, vaccine seroconversion, and infection of susceptibles, termed the force of infection, and to estimate the average age at first infection.

Adolescent↗
PubMed1993

The influence of age on the development of the hepatitis B carrier state.

The relation between the age at infection with hepatitis B virus (HBV) and the development of the carrier state is examined by using data from a number of published and unpublished surveys. A remarkably consistent relation was found. Infants infected perinatally (within the first 6 months of life) were found to have a high probability of becoming carriers (0.885; 95% C.L. 0.84-0.93). Over the infant and early childhood age classes there was found to be a sharp decrease in the proportion of infections which lead to the carrier state. By adulthood (over 15 years) the probability of developing the carrier status was found to be about 0.1. A model was fitted to the data by using maximum likelihood, which provides a good empirical description of the observed data and can be used to predict the expected probability of developing the carrier state given the age at infection. It is postulated that, as a result of this rapid decline in the probability of becoming a carrier during early childhood, a mass childhood immunization campaign, which will tend to postpone the average age at infection in the unvaccinated community, will have a disproportionately large impact on the rate of generation of new carriers.

Adolescent↗
PubMed1993

Modeling age- and time-specific incidence from seroprevalence:toxoplasmosis.

New forms of catalytic epidemic models were developed to estimate the incidence of primary toxoplasmosis infection from age- and time-specific seroprevalence data collected from persons aged 0-100 years in South Yorkshire, England, 1969-1990. Piecewise constant and exponential polynomial functions were used to assess the way in which incidence depended on age and time, and to guide the choice of parametric models suitable for prediction. Incidence estimates were biased unless both age- and time-dependence were allowed for. New findings on the epidemiology of this infection emerged. Incidence appears to have fallen sixfold between 1915 and 1970, but has remained stable for the last 20 years. There is a marked peak in incidence in childhood. The incidence throughout the childbearing period is currently estimated to be 0.07 or less per 100 susceptible persons per year. However, these predictions were highly sensitive to assumptions about incidence in childhood, and the 95% confidence limits for a range of models were between 0.003 and 0.32% per year. Age- and time-specific seroprevalence data can be collected inexpensively on a mass population basis, and, with appropriate incidence modeling, may prove to be a powerful method for the study of infectious disease and for incidence prediction.

Adolescent↗
PubMed1993

Modelling toxoplasma incidence from longitudinal seroprevalence in Stockholm, Sweden.

Age-stratified data on toxoplasma seroprevalence in pregnant women in Stockholm, Sweden for the years 1969, 1979 and 1987 provide the basis for an analysis of temporal patterns of Toxoplasma gondii infection, and estimation of the risk of maternal toxoplasmosis, in this population. A catalytic infection model, in which the rate or force of infection is assumed to be a function of time (and not, as is more usual, age), was employed to describe the observed changes in levels of toxoplasma seropositivity. A range of simple incidence functions (up to 3 parameters) were fitted using a method of maximum likelihood. The data were significantly better described by a linear or an exponential decay in the rate of infection through time compared with a constant level. More complex incidence functions gave no better data description. Thus, whilst there is strong evidence for declining incidence in Stockholm over the past 4-5 decades, the data do not allow discrimination between different possibilities for the nature of this decline. Based on these modelling results, best estimates of the force of infection in 1987 acting on susceptible women are within the range 0 to 0.0045/susceptible/year (95% confidence limits), yielding a possible risk of maternal toxoplasmosis of between 0 and 2.7 cases/1000 pregnancies. These values are shown to be significantly lower than estimates based upon an assumption of temporal stability in toxoplasma incidence, which may be of practical significance to public health policy.

Adolescent↗
PubMed1992

Longitudinal study of Toxoplasma seroprevalence in South Yorkshire.

Serum samples collected from individuals of a wide range of ages in South Yorkshire between 1969 and 1990 provided the basis for a longitudinal seroprevalence survey of Toxoplasma gondii antibodies. Sera numbering 3868 were screened for T. gondii specific antibodies using a commercial latex agglutination test. The resultant temporal series of serological profiles revealed a rise, with age, in seroprevalence, the rate of which showed a decrease through time. A plateau of around 40-50% prevalence was attained by the 41- to 45-year age-class in 1969 which was not approached until the 66- to 70-year class in the 1988-90 data set. This trend for decline in seroprevalence was confirmed by statistical analysis for the age range 21-60 years. These results may be indicative of a decrease in the rate of toxoplasma exposure in this study community over the 20-year period. The survey of 1988-90 provides a base-line profile of present-day seroprevalence in which 11% of individuals in the age range 16-45 years (roughly corresponding to the childbearing age-range) show evidence of past infection. The representative nature of the serum collection and public-health implications of these results are discussed.

Adolescent↗
PubMed1991

Vaccine safety versus vaccine efficacy in mass immunisation programmes.

In community-wide immunisation programmes against childhood infections there is a conflict between the interests of the individual (vaccine safety and efficacy) and the interests of the community (vaccine uptake and level of herd immunity). Studies suggesting that the complication rate is greater with the high efficacy Urabe Am 9 mumps vaccine than with the lower efficacy Jeryl Lynn vaccine, have led to concern about whether the higher efficacy mumps vaccine should be introduced or retained in nationwide mass immunisation programmes. We describe the use of a mathematical model to assess benefits and risks to both individual and community, and illustrate this method by reference to immunisation programmes based on these vaccines. On the basis of current epidemiological data on viral transmission and vaccine coverage in England and Wales, data on vaccine-associated and infection-associated complication rates, and vaccine efficacies estimated from clinical trials, our analyses suggest there is little to choose between the two vaccines, but that overall performance depends on the level of vaccine coverage in a defined population. In community-based programmes, the greater apparent safety of the Jeryl Lynn vaccine (fewer vaccine-induced complications) is offset by the greater apparent efficacy of the Urabe Am 9 vaccine (fewer complications due to natural infection). The findings suggest that it may not always be in the interests of the community to use the vaccine with the lowest complication rate.

Age Factors↗
PubMed1991

Model-based comparisons of measles immunization strategies using high dose Edmonston-Zagreb type vaccines.

The World Health Organization has recently made a new recommendation for measles immunization in areas with very high rates of transmission. The new policy will involve a switch to the high potency Edmonston-Zagreb (E-Z) vaccine (a strain with improved efficacy in the presence of maternally-derived, specific antibody), targeting immunization at six-month-old infants. We present a mathematical model of measles transmission that can be used to assess the likely impact of cohort immunization on the incidence of infection using the new strain of vaccine. Data requirements of the model are discussed, with special reference to the critical issue of age-specific vaccine efficacy. Currently available information on seroconversion rates achieved with the new strain are summarized. Results are presented which endorse the new WHO recommendations, predicting considerable benefits, in particular, to those most at risk of measles morbidity and mortality. Furthermore, integration of E-Z with the third diphtheria, pertussis, tetanus (DPT) dose at three-four months should be considered as an alternative option, particularly if combined with some additional coverage at nine months of age.

Humans↗
PubMed1990

Serological study of the epidemiology of mumps virus infection in north-west England.

Serum samples from individuals of a wide age range, collected in northwest England in 1984 and 1986, provide the basis for an analysis of the epidemiology of mumps virus infection. A radial haemolysis test yielding quantitative antibody measurements was used to screen samples for mumps-specific IgG. Analyses of resultant age-seroprevalence profiles, using statistical models, revealed an age-related pattern in the rate of infection per susceptible similar to that observed for other childhood infections. This rate, or force of infection, was low in young children, high in older children, and low in adults. In addition, the serological surveys provide evidence for time-dependent changes (both epidemic and longer-term) in the rate of mumps virus transmission. The longer-term changes, reflected in the pattern of the age-acquisition of specific antibodies, are supported by evidence from case notification data. The implications of temporal changes in incidence to the interpretation and design of serological surveys are considered.

Adolescent↗
PubMed1990

Measles immunization strategies for countries with high transmission rates: interim guidelines predicted using a mathematical model.

This study addresses the problem of measles immunization in communities experiencing unacceptably high numbers of cases in young infants, under circumstances where high dose Edmonston-Zagreb vaccine is not yet available. Where the continued use of standard potency vaccines (eg Schwarz) is unavoidable we have investigated the merits of new policies which aim to offer better protection to children below the currently recommended vaccination age of nine months. These policies are intended for implementation in communities with intense measles transmission. Predictions, spanning five years, using a previously developed mathematical model are presented for two types of potential new policies: a 'switch' to a younger target age, or a 'two-dose' strategy incorporating vaccination at a younger age in addition to the current schedule at nine months. We conclude that a switch in immunization policy to a younger age is of doubtful worth, but that supplementary vaccination at around six months in addition to existing coverage at nine months (ie two-dose policy) is a desirable option.

Age Factors↗
PubMed1989

Seroepidemiological study of the transmission of the mumps virus in St. Lucia, West Indies.

A seroepidemiological study of the prevalence of mumps virus specific antibodies reveals a pattern of endemic persistence on the island of St Lucia in the West Indies. In the unvaccinated population the proportion seropositive rose rapidly in the child age classes to attain a stable plateau close to unity in value in the teenage and adult age groups. The average age at infection was estimated to be between 3 and 4 years of age and the average duration of detectable levels of maternally derived antibodies was approximately 3 months. Analyses based on mathematical models of the transmission dynamics of the virus suggest that in excess of 75% of each cohort of 1- to 2-year-old children must be effectively immunized to eliminate mumps virus transmission. A mumps radial haemolysis test, developed for quantitative measurements of antibody, is discussed.

Adolescent↗