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D J Nokes

Publications and source records attributed to D J Nokes.

At least 19 recordsLinked to original sources
PubMed2000

Predictions of the emergence of vaccine-resistant hepatitis B in The Gambia using a mathematical model.

Vaccine escape variants of hepatitis B virus (HBV) have been identified world-wide. A mathematical model of HBV transmission is used to investigate the potential pattern of emergence of such variants. Attention is focused on The Gambia as a country with high quality epidemiological data, universal infant immunization and in which escape mutants after childhood infections have been observed. We predict that a variant cannot become dominant for at least 20 years from the start of vaccination, even when using a vaccine which affords no cross protection. The dominant factor responsible for this long time scale is the low rate of infectious contacts between infected and susceptible individuals (we estimate the basic reproduction number of hepatitis B in The Gambia to be 1.7). A variant strain that achieves high prevalence will also take many years to control, and it is questionable whether emergence will be identifiable by sero-surveillance until of high prevalence. The sensitivity of the model predictions to epidemiological and demographic factors is explored.

Adolescent↗
PubMed1999

Evaluating the cost-effectiveness of vaccination programmes: a dynamic perspective.

Although there are many models which are used to calculate the health benefits (and thus the cost-effectiveness) of vaccination programmes, they can be divided into two groups: those which assume a constant force of infection, that is a constant per-susceptible rate of infection; and those which assume that the force of infection (at time t) is a function of the number of infectious individuals in the population at that time (dynamic models). In constant force of infection models the per-susceptible rate of infection is not altered, whereas in dynamic models mass immunization results in fewer infectious individuals in the community and thus a lower force of infection acting on those who were not immunized. We take an example of each of these types of model, examine their underlying assumptions and compare their predictions of the cost-effectiveness of a mass immunization programme against a hypothetical close contact infection, such as measles. We show that if cases of infection are the outcome of interest then the constant force of infection model will always underestimate the cost-effectiveness of the immunization programme except at the extremes when no one or everyone is immunized. However, unlike the constant force of infection model, the dynamic model predicts an increase in the average age at infection after immunization which could impact on the estimate of the cost-effectiveness of the programme if the risk of developing serious disease is a function of the age at infection (as, for instance, is the case for congenital rubella syndrome). Taking cases of infection as the outcome measure and using the dynamic model, the undiscounted cost-effectiveness ratio will tend to decline over time and approach a constant value, as the system moves from pre- to post-immunization equilibrium. We go on to show how the cost-effectiveness of a fixed-term immunization programme might change over time, and discuss why, under most circumstances, decision makers should not assume that elimination (permitting termination of mass immunization) will occur.

Cohort Studies↗
PubMed1999

Modeling the impact of subclinical measles transmission in vaccinated populations with waning immunity.

An increasing body of evidence suggests that a substantial proportion of individuals who respond to measles vaccine display an antibody boost accompanied by mild or no symptoms on exposure to wild virus. It is unknown whether this emerging class of individuals can support transmission. The epidemiologic consequences of vaccinated individuals able to transmit virus are investigated using a mathematical model. Parameters for this model are estimated using regression analysis on a Canadian serologic data set. The authors confirm that neutralizing antibodies are decaying significantly in absence of circulating virus. Based on a protective threshold plaque reduction neutralization (PRN) titer of 120, the authors estimate the mean duration of vaccine-induced protection in absence of reexposure to be 25 years (95% confidence interval (CI) 18, 48). After long-term absence of circulating virus, the mathematical model predicts that 80% (95% CI 65, 91) of all seroconverted vaccinees have titers below the protective threshold. In this case, elimination of measles virus cannot be achieved by a single-dose routine vaccination strategy if the basic reproduction number in vaccinated individuals exceeds 1.24 (95% CI 1.10, 1.53). For this reason, there is a need to establish the intensity and duration of infectiousness in vaccinated individuals.

Adolescent↗
PubMed1999

Do we need 3 doses of hepatitis B vaccine?

The hepatitis B virus (HBV) vaccine may provide protection through the clonal expansion of specific memory cells without necessarily having to produce high serum antibody levels. We develop a mathematical model which distinguishes between the accumulation of sensitive memory B and T-helper cells prior to a booster and the high circulating antibody levels present in an individual after a booster. We suggest this immune memory accumulates primarily in an antigen-independent fashion. These phenomena suggest individuals may be immune to infection six months after the priming vaccine dose(s) regardless of whether they receive a booster or not. This hypothesis is supported by immunogenicity data and by two independent vaccine efficacy trials comparing 0, 1 month schedules with 0, 1 and 6 month schedules.

Hepatitis B Vaccines↗
PubMed1999

The predicted pattern of emergence of vaccine-resistant hepatitis B: a cause for concern?

We develop an epidemiological model of hepatitis B virus (HBV) in The Gambia in order to investigate the possible patterns of emergence of a vaccine-resistant strain. Under pessimistic assumptions (e.g., the current vaccine provides no cross-immunity against the variant) the model predicts the variant will not become dominant over the wild-type for at least 50 years. Therefore the current low prevalence of variant infections is not evidence for high cross-immunity of the vaccine or for low infectiousness of the variant, but may simply be a consequence of the epidemiology of HBV. The efficacy of the present vaccine against possible variants needs to be evaluated now to determine whether vaccine modifications are required. However, the model also suggests that serological surveillance may be unable to determine this efficacy for 40-50 years.

Adult↗
PubMed1999

A simplified and standardized neutralization enzyme immunoassay for the quantification of measles neutralizing antibody.

A simplified and standardized neutralization enzyme immunoassay (Nt-EIA) was developed to detect measles virus growth in Vero cells and to quantify measles neutralizing antibody. Heat-inactivated sera were diluted serially 4-fold and tested in duplicate. The 50% reduction point (50%RP) of virus growth was calculated using the Reed-Muench formula and the neutralizing antibody titre of test sera was converted into mIU/ml by comparing their 50%RP with that of the international standard serum. The optimal virus input and incubation time were found to be 50-100 plaque forming unit (PFU)/well and 64-72 h, respectively. The simplified Nt-EIA had a good reproducibility with only 3.7-4.2% of duplicate tests having a ratio > 4 in an evaluation of intra assay variation and the coefficients of variance were 2-9% in an evaluation of inter assay variation. In addition, the simplified Nt-EIA had a high sensitivity(98.6%), specificity (100%) and agreement (98.8%) in qualitative comparison with plaque reduction neutralization test (PRNT). In quantitative comparison, the correlation coefficient between Nt-EIA and PRNT was 0.83 without log transformation or 0.77 after log transformation and 90% of 61 positive sera had a ratio < 4 between antibody titre tested by the two methods. The simplified Nt-EIA is thus a suitable alternative to the PRNT for the quantification of measles neutralizing antibody.

Animals↗
PubMed1999

Detection of measles specific IgG in oral fluid using an FITC/anti-FITC IgG capture enzyme linked immunosorbent assay (GACELISA).

An IgG antibody capture enzyme linked immunosorbent assay (GACELISA) for the detection of measles specific IgG in oral fluid was developed using an FITC/anti-FITC amplification system. The GACELISA was evaluated by testing paired oral fluid and serum samples from 787 subjects in an epidemiological study of measles in rural Ethiopia. Oral fluids were tested by GACELISA and corresponding serum samples by a sensitive indirect ELISA for measles IgG (Behring Enzygnost). By comparison with the serum measles IgG assay, the oral fluid GACELISA had a sensitivity of 97.4% (95% confidence intervals: 95.9, 98.2) and a specificity of 90.0% (81.9, 94.3), with no significant differences observed by age group. Total IgG concentrations were measured on a subset of 160 oral fluids by an in-house ELISA. This showed that false negative GACELISA results tended to occur in samples with low concentrations of total IgG, although the trend was not statistically significant. It is concluded that the overall performance of the GACELISA was satisfactory, showing close agreement to the serum ELISA, and has potential to serve as an easily transferable tool for large scale epidemiological studies as required for the World Health Organisation's programme for the global control of measles.

Antibodies, Viral↗
PubMed1999

Detection of rubella virus-specific immunoglobulin G in saliva by an amplification-based enzyme-linked immunosorbent assay using monoclonal antibody to fluorescein isothiocyanate.

An immunoglobulin G (IgG)-capture enzyme-linked immunosorbent assay (ELISA) for rubella virus is described. The assay uses a fluorescein isothiocyanate (FITC)-anti-FITC amplification system. The detection limit of the ELISA was approximately 7 IU of rubella virus-specific IgG per ml of serum sample. For saliva samples the performances of the capture ELISA and previously described radioimmunoassay were assessed, and the results of those two assays were compared to the rubella virus-specific IgG result obtained by a commercial ELISA (Behring Enzygnost) with a panel of paired serum and saliva samples. This comparison showed that the capture ELISA with saliva was more sensitive than the radioimmunoassay and that the results correlated better with the serum IgG result than the results of the radioimmunoassay did, with an overall sensitivity of 82% and a rank correlation of 0.68, whereas the sensitivity and rank correlation for the radioimmunoassay were 74% and 0.45, respectively. For subjects of 10 years of age or younger, the ELISA with saliva had a sensitivity of 94% and a specificity of 100% compared to the results of the ELISA (Behring Enzygnost) for rubella virus-specific IgG with corresponding serum samples. The sensitivity was much lower for subjects ages 17 years or older. The assay may have wider epidemiological use with saliva specimens, particularly those from children.

Adolescent↗
PubMed1998

Age- and sex-specific HIV-1 prevalence in the urban community setting of Addis Ababa, Ethiopia.

OBJECTIVE: To estimate the age and sex-specific prevalence of HIV infection in the population of Addis Ababa, Ethiopia. DESIGN: Two-stage cluster sampling of the population aged 0-49 years of Addis Ababa, using kebeles (urban dwelling associations) as clusters. METHODS: The sera used for this study were collected in an earlier study (1994) on the rate of acquisition of antibodies against measles, rubella, and hepatitis B. After separate approvals were obtained from the institutional ethics committees, sera were tested by enzyme-linked immunosorbent assay confirmed by Western blot. Age- and sex-specific HIV prevalence rates were estimated. The prevalence of HIV in men and women over 15 years of age was compared by calculating age-standardized HIV prevalence, using the age distribution of the census population as the standard. A time-dependent catalytic model was used to obtain crude estimates of HIV incidence from age-prevalence data. RESULTS: A total of 3853 sera were available for analysis. The prevalence of HIV in adults was 6.0% [95% confidence interval (CI), 4.5-7.4%] for men and 6.9% (95% CI, 5.3-8.5%) for women, with peak prevalence in the 25-29 year age group of 16.3 and 11.8%, respectively. After standardization for age using the direct method, the HIV prevalence ratio comparing adult men with women was 0.97:1 (95% CI, 0.70:1 - 1.35:1). Three children aged less than 5 years were HIV-positive. The prevalence of HIV among adults ranged from 0-21.3% in different clusters, indicating the heterogeneity of the spread of HIV in the city. HIV prevalence estimates among the antenatal clinic patients of Addis Ababa in 1996 far exceeded the estimates obtained during the community survey, particularly in the youngest age group (15-24 years). Estimates of HIV incidence (per susceptible person per annum) for the age group 16-22 years ranged from 1.3-2.25% for men and from 2.1-2.4% for women. CONCLUSION: By 1994, a substantial proportion of the adult population of Addis Ababa was infected with HIV. Promotion of behavioural changes and the control of sexually transmitted diseases should be strongly supported to limit the spread of the HIV epidemic in Ethiopia.

Adolescent↗
PubMed1998

Seroepidemiology of group A rotavirus in suburban São Paulo, Brazil.

Age-specific patterns of rotavirus infection were investigated using a randomly selected and representative sample of sera from a suburban community of São Paulo, Brazil screened for class-specific antibodies to group A rotavirus. Age-serology of anti-rotavirus IgG showed primary infection predominant in young infants with a median age of around 18 months consistent with IgM serology suggesting highest rates of recent infection between ages 4 and 48 months. Anti-rotavirus serum IgA prevalence increased gradually with age. Paired samples from infants, collected 1 month apart, indicated high exposure rates with seroconversion occurring in several infants during the reported low transmission season. Between 5 and 10% of adults had elevated IgM levels indicative of recent infection and, potentially, of an important contribution adults may play to rotavirus transmission. Further understanding of the dynamics of rotavirus transmission within populations, at group and serotype level, would benefit the design and monitoring of future immunization programmes.

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↗
PubMed1998

Current status of HBV vaccine escape variants--a mathematical model of their epidemiology.

We present a deterministic model of the possible emergence of a vaccine escape variant of hepatitis B virus (HBV). The model identifies the key unknowns determining this process: the protection afforded by the current vaccines against particular HBV variants; the infectiousness of these variants; and the current prevalence of individuals infectious with the variants (each factor relative to wild-type). By making pessimistic assumptions about these unknowns we show that even a highly infectious variant, under a vaccine programme that affords no protection against the variant, would still take decades to emerge. Thus the current low prevalence of variants is not evidence for the cross-reactivity of the current vaccines or for a lack of infectiousness in the variants. As any vaccine failure will be inapparent for decades it may be sensible to recommend vaccine modifications now rather than later.

Hepatitis B Vaccines↗
PubMed1998

A comparison of oral fluid and serum for the detection of rubella-specific antibodies in a community study in Addis Ababa, Ethiopia.

OBJECTIVE: To assess the utility of oral fluid compared with serum for the determination of age-prevalence of rubella-specific antibodies in an urban African community setting. METHOD: Paired serum and oral fluid samples were collected from 439 individuals aged 0-49 years in Addis Ababa, Ethiopia, as part of a larger seroepidemiological survey in 1994. Oral fluid was sampled using a simple sponge device that was well accepted by subjects of all ages; venous blood was collected by Vacutainer system. We measured rubella-specific antibodies in serum by the Radial Haemolysis (RH) test, supported by two confirmatory assays, and in oral fluid by IgG antibody-capture radioimmunoassay (GACRIA). RESULTS: Sensitivity and specificity of oral fluid results compared to serum were 89% and 76%, respectively. Sensitivity declined from 96% in age group 0-19 years to 90% in age group 20-29 and 78% in age group 30-49. Specificity was 86% in 0-9 year olds contrasting with 61% in older groups (10-49 years). The positive predictive value of an oral fluid sample was high in all age groups (range 92-100%), while the negative predictive value declined from > or =80% in those aged <10 years to <10% in those aged > or =30 years. Serum confirmatory tests suggested a proportion of false serum RH negatives, increasing with age, indicating a need to standardize serum as well as oral fluid tests. CONCLUSION: In the community setting of a developing country, oral fluid surveys could be useful to estimate age-prevalence of rubella immunity and identify rubella-susceptible children for follow-up. Further work is required to simplify assays and sample processing, improve assay sensitivity and estimate assay specificity more precisely, and compare and standardise collection methods suitable for surveillance of a variety of childhood viral infections.

Adolescent↗
PubMed1997

Who mixes with whom? A method to determine the contact patterns of adults that may lead to the spread of airborne infections.

Although mixing patterns are thought to be important determinants of the spread of airborne infectious diseases, to our knowledge, there have been no attempts to directly quantify them for humans. We report on a preliminary study to identify such mixing patterns. A sample of 92 adults were asked to detail the individuals with whom they had conversed over the period of one, randomly assigned, day. Sixty-five (71%) completed the questionnaire, providing their age, the age of their contacts and the social context in which the contacts took place. The data were analysed using multilevel modelling. The study identified, and allowed the quantification of, contact patterns within this sample that may be of epidemiological significance. For example, the degree of assortativeness of mixing with respect to age was dependent not only on the age of participants but the number of contacts made. Estimates of the relative magnitude of contact rates between different social settings were made, with implications for outbreak potential. Simple questionnaire modifications are suggested which would yield information on the structure and dynamics of social networks and the intensity of contacts. Surveys of this nature may enable the quantification of who acquires infection from whom and from where.

Adult↗
PubMed1997

A comparison of fertility control and lethal control of bovine tuberculosis in badgers: the impact of perturbation induced transmission.

In this paper we use mathematical modelling to consider the broad advantages and disadvantages of fertility control over lethal control for bovine tuberculosis in badger populations. We use a deliberately simple model, attempting to capture only the key transmission processes. The model is parametrized with reference to the long-term Woodchester Park study. Estimates of mortality rate from this study suggest no significant extra mortality risk for animals with evidence of infection as indicated by the presence of anti-Mycobacterium bovis antibodies or M. bovis isolation. We find that large reductions in prevalence are sometimes the consequence of only moderate reductions in population numbers. If we assume that the act of control does not in itself affect transmission rates, then as far as eradication is concerned, both fertility control and mortality control operate through the same epidemiological mechanism, the removal of susceptibles: if one is in principle capable of keeping a population low enough to be infection free then so is the other. It is necessary to continue either form of control at regular intervals to maintain a constant level of infection in the long term. If control were to be stopped, return to precontrol levels of badger population and infection prevalence would be expected within a few years. Fertility control is less effective in reducing population density than lethal control since it can only act, at maximum, to remove one age cohort per year. It is also less effective in reducing transmission as it can only ever remove susceptibles, while lethal control also removes infectious badgers. However, if the social disturbance caused by lethal control does in fact increase contact rates for the remaining infectious badgers, the relative efficacies of the two strategies become a great deal less clear. While we have no quantitative data on the extent to which social perturbation does act to promote transmission, model simulations show that it is possible to develop plausible scenarios in which the lethal control may actually act to increase the absolute numbers of animals infected, while reducing the number of uninfected animals to very low numbers.

Animals↗
PubMed1997

Vaccination in pulses: a strategy for global eradication of measles and polio?

Recent American successes against poliomyelitis and measles have been attributed to repeated 'pulse' vaccination campaigns. Whilst logistic and economic constraints will be crucial, a deeper epidemiological understanding of the mechanism, strengths and weaknesses of pulse vaccination will optimize the chances of success elsewhere in the world.

Age Factors↗
PubMed1996

The transmission dynamics and control of hepatitis B virus in The Gambia.

A deterministic, compartmental, mathematical model is used to describe the transmission dynamics of hepatitis B virus (HBV) in a high endemicity country. All three major transmission routes are included in the model, that is, perinatal, horizontal and sexual transmission. The model also reflects the demography of a typical developing country, and incorporates age-dependence in the rates of transmission and the probability of becoming a chronic carrier. Numerical simulations of the model are shown to capture the observed age-specific patterns of serological markers. The sensitivity of the model to age-specific heterogeneities and routes of transmission is investigated. The model is used in a preliminary study of the possible implications of mass infant immunization on HBV epidemiology, and the results suggest that eradication of HBV may be achieved by immunizing less than 70 per cent infants, which is relatively low compared to most childhood viral infections. This is due in part to the interaction between changes to the average age at infection under immunization, and the nature of age-dependence in the force of infection and the probability of becoming a carrier. However, numerical results also suggest that eradication may take many decades to be achieved, largely due to the presence of a pool of chronic carriers. Furthermore, there may be a significant lag between the implementation of mass infant immunization and a decline in the incidence of liver cancer.

Adolescent↗