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Biomedical subjects

A E Ades

Publications and source records attributed to A E Ades.

At least 55 records · Page 3Linked to original sources
PubMed1997

A method for the detection and confirmation of antibodies to hepatitis C virus in dried blood spots.

This study describes the development and evaluation of a cost effective test rationale for the detection of anti-HCV in dried blood spots. Samples were screened using an 'in house' IgG ELISA that incorporated the recombinant proteins c22-3, c200 and NS5. Confirmation of specific antibody to HCV was by a modification of the immunoblot RIBA 3.0. An extensive panel of well evaluated anti-HCV positive and negative samples from the UK and South Africa were used to assess the sensitivity and specificity of the two tests. One third of the anti-HCV positive samples had been typed. All anti-HCV positive samples were detected by the 'in house' screening EIA. Test/negative optical density ratios showed that more than 95% of reactive samples produced values greater than 5.0. Antibodies to HCV could be detected in a wide range of samples derived from asymptomatic and symptomatic patients and of different genotypes, with similar sensitivity. The presence of anti-HCV could be confirmed by RIBA 3.0 in samples with low reactivity but not in anti-HCV negative samples. Furthermore the immunoblot assay successfully increased specificity by screening out false reactive EIA samples that might occur in an epidemiological survey of a multi-ethnic population.

Adult↗
PubMed1997

Uptake of interventions to reduce mother-to-child transmission of HIV in the United Kingdom and Ireland.

OBJECTIVES: To describe the uptake of interventions to reduce mother-to-child transmission of HIV infection. DESIGN: Voluntary confidential reporting of HIV infection in pregnancy and childhood; telephone interview with key professionals in all London maternity units. SUBJECTS AND SETTING: HIV-infected pregnant women and children in the United Kingdom and Ireland. MAIN OUTCOME MEASURES: Trends in breastfeeding, use of zidovudine, mode of delivery and terminations of pregnancy. RESULTS: Between 1990 and 1995, 14 (4%) out of 314 women diagnosed with HIV infection before delivery breastfed compared with 109 (77%) out of 142 diagnosed after delivery. Since 1994, zidovudine use has increased in each 6-month period (14, 39, 67, and 75%; chi 2 = 17.5, P < 0.001), although in 1995 it was the policy of only 48% of London maternity units to offer zidovudine to HIV-infected women. During 1995, 44% of HIV-infected women were delivered by elective Cesarean section. Since 1990, 20% of women first diagnosed in pregnancy were reported to have their pregnancy terminated. CONCLUSIONS: Although detection of previously undiagnosed HIV infection in pregnancy remains low in the United Kingdom, and particularly in London, HIV-infected pregnant women who are aware of their status are increasingly active in taking up interventions to reduce transmission to their infants. If all HIV-infected women attending for antenatal care in London consented to testing and took up interventions and termination of pregnancy at the rates observed in this study, the number of vertically infected babies born in London each year could be reduced from an estimated 41 to 13.

Abortion, Induced↗
PubMed1997

Malignancies in UK children with HIV infection acquired from mother to child transmission.

By April 1995, 302 cases of vertically acquired HIV infection had been reported through the British Paediatric Association Surveillance Unit. Over 50% of these children had developed an AIDS indicator disease, including nine malignancies (seven cases of non-Hodgkin's lymphoma (NHL) and two of Kaposi's sarcoma). There were two other malignancies that were not AIDS indicator diseases. In children less than 5 years of age the incidence of NHL was approximately 2500 times greater than expected in the UK child population. Three children presented with NHL as their AIDS indicator disease and four developed NHL at a median of 14 (range 10-19) months after the initial diagnosis of AIDS. Six of the seven children died at a median of 6.5 (range 2-14) months after the diagnosis of NHL. The seventh child responded to treatment and is alive nearly four years later. Histology was available in five cases, of which four were of B cell and one of T cell origin. Epstein-Barr virus was detected in all three patients with NHL where it was sought; all had B cell lymphomas. Although comparatively rare, malignancies occur in children infected with HIV and may be the presenting illness. Paediatricians now need to consider HIV infection as a predisposing cause of childhood cancer, especially NHL.

Child, Preschool↗
PubMed1996

Risk factors for recent toxoplasma infection in pregnant women in Naples.

Effective primary prevention of congenital toxoplasmosis requires up to date information on locally relevant risk factors for infection in pregnant women. In Naples, risk factors for toxoplasma infection were compared in recently infected women (as assessed by detection of specific IgM in serum) and susceptible, IgG negative women. Recent infection was strongly associated with frequency of consumption of cured pork and raw meat. Eating cured pork or raw meat at least once a month increased the risk of toxoplasma infection threefold. This simple study design for determining locally relevant sources of toxoplasma infection is the first report of cured pork as a risk factor for infection. Further research is required to determine cyst viability in cured pork products. Our findings suggest that in southern Italy, cured pork and raw meat should be avoided by susceptible pregnant women.

Adult↗
PubMed1995

Serial HIV seroprevalence surveys: interpretation, design, and role in HIV/AIDS prediction.

To examine the potential role of seroprevalence surveys in HIV epidemic analysis and prediction, seroprevalence was modeled in terms of age- and time-specific incidence, while taking account of the differential inclusion of infected and uninfected individuals in serosurveys. Differential inclusion had two components, one reflecting disease progression and the other background demographic factors that could change over time. Seroprevalence and progression marker data generated by simulated epidemics showed that age dependence in HIV incidence is a key factor in data interpretation. Time trends in seroprevalence are difficult to interpret, and incidence cannot be estimated from these data unless the effects of disease progression on inclusion are taken into account. Furthermore, changes in incidence could be hard to distinguish from changes in background differential inclusion, casting doubt on the value of smaller sentinel surveys. Uncertainty about differential inclusion severely limits the value of seroprevalence data in improving the precision of HIV/AIDS prediction. Progression marker data are even harder to interpret, since changes in incidence will have effects on the marker value distribution, the size, direction, and timing of which are highly age-dependent. Independent data on differential inclusion would enhance the value of data from seroprevalence surveys.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Coverage of routine neonatal metabolic screening in children born to women known to be infected with HIV-1.

Unlinked anonymous HIV-1 testing of neonatal samples routinely collected for metabolic screening is now carried out in many parts of the United Kingdom. The purpose of this study was to assess the completeness of screening coverage in infants born to women known to be infected with HIV-1. Research nurses at family HIV clinics in three London hospitals searched for Guthrie cards from all infants born to known infected residents of North East, North West, and South West Thames regions over a 32 month period. If no card was found initially, mothers were approached for more information. Overall coverage was estimated to be 96.4% (94.6% in infants of African origin and 100% in white infants). These figures are similar to recent general population coverage estimates in inner London. We conclude that the anonymous newborn HIV testing programme is providing sufficiently accurate information on both absolute levels and time trends in maternal seroprevalence.

Africa↗
PubMed1995

Age-related standards for ordinal data: modelling the changes in visual acuity from 2 to 9 years of age.

The visual acuities of 1140 children between the ages of 2 and 9 years were measured using the Sonksen-Silver Acuity System (SSAS) from a distance of 3 metres. Ordered logistic regression was used to construct smoothly changing age-related reference ranges for the proportions of children at different ages expected to have acuities in each of three ordinal categories. Exponential functions of age fitted the data better than polynomials. The resulting reference ranges can be used to derive the ages at which a given percentage of children achieve each of the acuity cut-offs. However, since it is unlikely that all children will be available for testing at the exact appropriate age, two possible alternatives are introduced and discussed. First, a new ordinal category that would result in a chosen outcome at a pre-selected age is calculated. Secondly, because it may be more feasible to use the current SSAS system whilst varying the distance of measurement, age-related standards showing the distances required to give constant pass-rates with the usual letter-sizes are also presented.

Age Factors↗
PubMed1995

Use of dried blood spots for the detection and confirmation of HTLV-I specific antibodies for epidemiological purposes.

AIMS--To modify and evaluate a gelatin particle agglutination test that could provide a sensitive, specific and inexpensive method for the detection of HTLV-I antibody in dried blood spot samples (DBS) collected on filter paper. METHODS--A set of 26 reference samples confirmed as HTLV-I antibody positive were assembled from patients with tropical spastic paraparesis or adult T cell leukaemia and blood donors. Serum samples and simulated antibody positive dried blood spot eluates were tested using the Serodia assay together with two confirmatory tests: HTLV BLOT 2.3, a western blot, and Select-HTLV, an enzyme immunoassay (EIA). Both confirmatory tests use synthetic peptides to differentiate between antibodies to HTLV-I and -II. The modified Serodia assay was then used to test anonymously 10,135 DBS collected from neonates from London. Samples reactive in the modified Serodia test producing a positive result were titrated to an end point and confirmed as before. RESULTS--All 26 eluates made from simulated DBS derived from positive reference samples were identified as positive by the modified Serodia HTLV-I test and were confirmed as anti-HTLV-I positive by EIA. Two eluates derived from relatively low titre reference samples gave indeterminate results on western blotting. Screening of the 10,135 neonatal DBS resulted in six repeat reactives, five of which were confirmed. The remaining reactive sample gave an indeterminate result on western blotting and there was insufficient eluate for testing by EIA. The overall seroprevalence of HTLV-I in this population was 0.05% (five of 10,135). CONCLUSION--The modified Serodia HTLV-I assay provides a sensitive, specific and inexpensive (10 pence/test) method for screening large numbers of DBS. The format of the assay makes it ideally suited for simultaneous screening of antibodies to HIV-1, HIV-2 and HTLV-I using semi-automated equipment.

Adult↗
PubMed1994

Age-related reference ranges: significance tests for models and confidence intervals for centiles.

A method of fitting age-related reference ranges using maximized likelihood is presented. The method is illustrated using CD4 counts of uninfected children born to HIV-1 infected women. The likelihood incorporates exponential functions to describe the Box-Cox transformation parameter that induces Normality and the mean and standard deviation of the transformed data, at all ages in the range. This guarantees that the centiles are asymptotic to notional adult values and avoids edge effects. Likelihood ratio tests were used to assess the significance of the model parameters, and profile likelihood confidence intervals were constructed around the fitted centiles. The asymptotes of the resulting CD4 reference range for the childhood dataset were compared with CD4 counts available from a group of uninfected adults. The proposed approach limits the need for arbitrary decisions about grouping of the data, degree of smoothing or choice of model.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Estimates of disease incidence in women based on antenatal or neonatal seroprevalence data: HIV in New York City.

Piecewise constant incidence models were developed to estimate the force of infection in women from age- and time-specific antenatal or neonatal seroprevalence data. Differential inclusion of infected women in sero-surveys compared to uninfected women was taken into account, with respect to both changes in inclusion rate following infection, and changes in relative inclusion rate over calendar time. These models were applied to anonymous HIV seroprevalence data collected from neonates born to black and Hispanic women in New York City 1988-1992, with incidence and fertility parameters estimated by maximum likelihood. Estimates of inclusion rate parameters accorded well with what is known about the natural history of HIV. The data could not distinguish between additive and multiplicative combination of the effects of age and time on incidence. Incidence was strongly dependent on age with the highest incidence in women aged 20-34 years. There was strong evidence that incidence had been falling in Hispanic women since 1982-1984. The results illustrate the extent to which trends in incidence over time may be confounded by changes in the relative inclusion rate of infected and uninfected women.

Adolescent↗
PubMed1994

Relation between biochemical severity and intelligence in early treated congenital hypothyroidism: a threshold effect.

OBJECTIVES: To assess whether early treatment of congenital hypothyroidism fully prevents intellectual impairment. DESIGN: A national register of children with congenital hypothyroidism who were compared with unaffected children from the same school classes and matched for age, sex, social class, and first language. SETTING: First three years (1982-4) of a neonatal screening programme in England, Wales, and Northern Ireland. SUBJECTS: 361 children with congenital hypothyroidism given early treatment and 315 control children. MAIN OUTCOME MEASURES: Intelligence quotient (IQ) measured at school entry at 5 years of age with the Wechsler preschool and primary scale of intelligence. RESULTS: There was a discontinuous relation between IQ and plasma thyroxine concentration at diagnosis, with a threshold at 42.8 nmol/l (95% confidence interval 35.2 to 47.1 nmol/l). Hypothyroid children with thyroxine values below 42.8 nmol/l had a mean IQ 10.3 points (6.9 to 13.7 points) lower than those with higher values and than controls. None of the measures of quality of treatment (age at start of treatment (range 1-173 days), average thyroxine dose (12-76 micrograms in the first year), average thyroxine concentration during treatment (79-234 nmol/l in the first year), and thyroxine concentration less than 103 nmol/l at least once during the first year) influenced IQ at age 5. CONCLUSIONS: Despite early treatment in congenital hypothyroidism the disease severity has a threshold effect on brain development, probably determined prenatally. The 55% of infants with more severe disease continue to show clinically significant intellectual impairment; infants with milder disease show no such impairment. The findings predict that 10% of early treated infants with severe hypothyroidism, compared with around 40% of those who presented with symptoms in the period before screening began, are likely to require special education.

Child, Preschool↗
PubMed1994

Use of anonymous newborn serosurveys to evaluate antenatal HIV screening programmes.

OBJECTIVE: To evaluate the extent to which antenatal HIV screening programmes identify HIV infected women who go to term. DESIGN: Comparison of results of two surveillance systems. An anonymous neonatal HIV serosurvey was used to estimate the numbers of HIV infected women giving birth; reporting by obstetricians was used to assess the proportion who had been identified. SETTING: Three Thames regions. RESULTS: 729,105 neonatal blood samples were tested, of which 484 were HIV seropositive. Newborn HIV seroprevalence is increasing, at different rates, in inner London, suburban London, and in non-metropolitan districts. During the past four years the proportion of infected women who have been identified before delivery is 16.9%, but less than half of these were diagnosed during pregnancy. In 1993 only five of the 128 (4%) previously undiagnosed infected women delivering babies were identified by antenatal screening. CONCLUSION: Despite increased emphasis on antenatal testing for HIV in areas of higher prevalence the number of undiagnosed women delivering babies continues to increase. Consideration should be given to alternative strategies for offering antenatal HIV testing. Antenatal screening programmes should be monitored continuously by comparing anonymous neonatal seroprevalence with clinical reports from obstetricians.

Confidence Intervals↗
PubMed1993

Vertically transmitted HIV infection in the British Isles.

OBJECTIVE: To describe the epidemiology of vertically acquired HIV infection in the British Isles, the level of underreporting, the vertical transmission rate, and clinical spectrum of paediatric AIDS. DESIGN: Confidential, linked registers based on reporting from obstetricians and paediatricians; anonymous unlinked neonatal HIV serosurveys. SETTING: British Isles. SUBJECTS: Children born to mothers with HIV infection. MAIN OUTCOME MEASURES: Trends in HIV infection and vertical transmission rate. RESULTS: In Scotland and the Irish Republic, where most maternal HIV infection is related to drug misuse, the annual number of reports of children born to infected mothers has fallen since 1989. In England and Wales nearly half of maternal infections have been acquired overseas, and the number of children born to these women, and to women who became infected in Britain, is increasing. In south east England the proportion of live births to women whose infection was identified before delivery was only 17% (50/287), compared with 68% (26/38) in Scotland. The vertical transmission rate was 13.7% (23/168), and 23% of infected children developed AIDS in the first year of life. 41% (38/92) of children born to infected mothers who were ascertained after delivery were breast fed, compared with 5% (12/236) of those ascertained before delivery. CONCLUSIONS: The incidence of vertically transmitted HIV infection is increasing in England and Wales. More extensive antenatal testing would enable infected women to be counselled against breast feeding, which could prevent a substantial proportion of vertical transmission in some areas, and would increase opportunities for early diagnosis and treatment of infected children.

AIDS-Related Opportunistic Infections↗
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

Maternal prevalence of Toxoplasma antibody based on anonymous neonatal serosurvey: a geographical analysis.

A total of 12,902 neonatal samples collected on absorbent paper for routine metabolic screening were tested anonymously for antibodies to toxoplasma. Seroprevalence varied from 19.5% in inner London, to 11.6% in suburban London, and 7.6% in non-metropolitan districts. Much of this variation appeared to be associated with the proportions of livebirths in each district to women born outside the UK. However, additional geographical variation remained and seroprevalence in UK-born women was estimated to be 12.7% in inner London, 7.5% in suburban London, and 5.5% in non-metropolitan areas. These estimates are considerably lower than any previously reported in antenatal sera in the UK. The wide geographical variation highlights a need for further research to determine the relative importance of different routes of transmission.

Antibodies, Protozoan↗
PubMed1993

Birth weight and body mass index in childhood, adolescence, and adulthood as predictors of blood pressure at age 36.

STUDY OBJECTIVE: The purpose of this study was to investigate the relation between blood pressure at age 36, and birth weight and body mass index (BMI) in childhood, adolescence and adulthood. DESIGN: Prospective longitudinal survey over a period of 36 years in England, Scotland, and Wales. PARTICIPANTS: A nationally representative sample consisting of 3332 men and women born in one week in March 1946. Altogether 82% of these subjects had complete data for the present analysis. MAIN RESULTS: There was an inverse linear relation between birth weight and blood pressure at age 36. The relation between BMI and blood pressure at age 36 was initially inverse and became increasingly positive throughout life. Weight gain in childhood was positively associated with adult blood pressure, although less important than weight change in later life. The associations between blood pressure and birth weight, and blood pressure and adult BMI were independent, and together they accounted for no more than 4% of the variation in adult blood pressure. Both low birth weight (birth weight < or = 2.5kg) and high BMI at age 36 (BMI > 30kg/m2) were associated with hypertension (> 140/90mmHg), but the per cent population risk of hypertension attributable to low birth weight was less than 5%, and to high BMI less than 12%. CONCLUSIONS: Low birth weight and high BMI at age 36 were independently related to high blood pressure. A reduction in the percentage of low birthweight babies born in the fourth decade of this century would only have a negligible effect on the incidence of adult hypertension 30-40 years later.

Age Factors↗