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D J Nokes

Publications and source records attributed to D J Nokes.

At least 37 records · Page 2Linked to original sources
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↗
PubMed1996

Dynamical complexity in age-structured models of the transmission of the measles virus: epidemiological implications at high levels of vaccine uptake.

This article explores the effect of increasingly finely stratified age structure on the dynamical properties of deterministic metapopulation models of the transmission of the measles virus. The dynamical simplicity of earlier age-structured models is shown to break down once the age-specific force of infection is no longer assumed to be constant across all child age classes below 5 years of age. While the biennial epidemics characteristic of earlier models are still observed, additional higher period stable cycles arise and coexist with the biennial cycle. The existence of multiple stable limit cycles necessarily implies model sensitivity on initial conditions, and for certain parameter values, chaotic dynamics are observed. Using a novel parameterization of the magnitude of seasonal forcing we are also able to make more biologically relevant comparisons between the dynamics of age- and non-age-structured models than have hitherto been possible. The epidemiological significance of these results is discussed, and we demonstrate that perturbations of the kind produced by intensive vaccination programs can shift transmission dynamics between biennial and triennial cycles. The possible implications of this work for studies of intermittency and infection persistence are also considered.

Adolescent↗
PubMed1996

Epidemiological patterns of hepatitis B virus (HBV) in highly endemic areas.

This paper uses meta-analysis of published data and a deterministic mathematical model of hepatitis B virus (HBV) transmission to describe the patterns of HBV infection in high endemicity areas. We describe the association between the prevalence of carriers and a simple measure of the rate of infection, the age at which half the population have been infected (A50), and assess the contribution of horizontal and perinatal transmission to this association. We found that the two main hyper-endemic areas of sub-Saharan Africa and east Asia have similar prevalences of carriers and values of A50, and that there is a negative nonlinear relationship between A50 and the prevalence of carriers in high endemicity areas (Spearman's Rank, P = 0.0086). We quantified the risk of perinatal transmission and the age-dependent of infection to allow a comparison between the main hyper-endemic areas. East Asia was found to have higher prevalences of HBeAg positive mothers and a greater risk of perinatal transmission from HBeAg positive mothers than sub-Saharan Africa, though the differences were not statistically significant. However, the two areas have similar magnitudes and age-dependent rates of horizontal transmission. Results of a simple compartmental model suggest that similar rates of horizontal transmission are sufficient to generate the similar patterns between A50 and the prevalences of carriers. Interrupting horizontal transmission by mass immunization is expected to have a significant, nonlinear impact on the rate of acquisition of new carriers.

Adult↗
PubMed1996

The transmission dynamics of hepatitis B in the UK: a mathematical model for evaluating costs and effectiveness of immunization programmes.

Complex hepatitis B (HBV) epidemiology makes it difficult to evaluate and compare effectiveness of different immunization policies. A method for doing so is presented using a mathematical model of HBV transmission dynamics which can represent universal infant and adolescent vaccination strategies and those targeted at genito-urinary (GU) clinic attenders and infants born to infectious mothers. Model structure, epidemiological underpinning, and parameterization, are described. Data from the UK National Survey of Sexual Attitudes and Lifestyles is used to define patterns of sexual activity and GU clinic attendance; data deficiencies are discussed, in particular that of UK seroprevalence of HBV markers stratified by age, sex, and risk factors. General model predictions of endemic HBV marker prevalence in homosexual and heterosexual populations seem consistent with published UK data. The simulations exhibit non-linearities in the impact of different vaccination strategies. Estimated number of carriers prevented per vaccine dose for each strategy provides a measure of costs and benefits, varying temporally over the course of a programme, and with level of vaccine coverage. Screening before vaccination markedly increases payback per dose in homosexuals but not in heterosexuals; mass infant vaccination gives the poorest effectiveness ratio and vaccination of infants after antenatal screening the best; in general, increasing vaccine coverage yields lower pay-back per dose. The model provides a useful framework for evaluating costs and benefits of immunization programmes, but for precise quantitative comparison more UK epidemiological data is urgently needed.

Adolescent↗
PubMed1996

Targeted hepatitis B vaccination--a cost effective immunisation strategy for the UK?

OBJECTIVE: To compare the potential cost effectiveness of vaccination against hepatitis B virus (HBV) targeted at genitourinary clinic (GU) attendees with that of universal infant vaccination. DESIGN: A mathematical model of sexual and perinatal transmission of HBV was used to compare the effectiveness among heterosexual and homosexual populations of programmes of mass infant vaccination and targeted immunisation of genitourinary medicine (GU) clinic attendees. Each was applied to 90% of the eligible population with differing assumptions about rates of compliance and seroconversion - problems of delivery (obtaining high compliance) was considered a significant drawback of targeted vaccination. Observed relationships between GU clinic attendance and sex partner change rates for heterosexuals and for homosexuals were used to define the rates of vaccination uptake within sexual activity risk groups. SETTING: England and Wales. RESULTS: Model results showed that for heterosexuals universal infant vaccination became more effective than clinic based vaccination only approximately 40 years after the start of the programme and that the predicted cost effectiveness of GU clinic vaccination was greater at all times. For homosexuals, clinic vaccination was always more effective over the time frame considered, but by 50 years if it were carried out without prior screening it had become appreciably less cost effective than a mass infant programme. With prior screening in GU clinics this cost effectiveness deficit was only marginal. CONCLUSIONS: Targeted vaccination might have a much greater potential than is realised at present, particularly if it were possible to improve compliance of clinic attendees. A fuller comparison between mass infant and targeted vaccination must await the specific inclusion in the model of other risk groups such as intravenous drug users. An important determinant of the relative merits of the two approaches is the relationship between rates of attendance and of changing sexual partners. Further research on this is required.

Adult↗