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Biomedical subjects

A E Ades

Publications and source records attributed to A E Ades.

At least 19 recordsLinked to original sources

Risk of human immunodeficiency virus type 1 transmission through breastfeeding.

Detection of human immunodeficiency virus type 1 (HIV-1) in breast milk by culture and polymerase chain reaction does not necessarily mean that breastfeeding is a route of transmission, although evidence from several case-reports points in that direction. We undertook a systematic review of published studies meeting criteria that allowed determination of quantitative risk of transmission via breastfeeding. Based on four studies in which mothers acquired HIV-1 postnatally, the estimated risk of transmission is 29% (95% Cl 16-42%). Analysis of five studies showed that when the mother was infected prenatally, the additional risk of transmission through breastfeeding, over and above transmission in utero or during delivery, is 14% (95% Cl 7-22%). Where there are safe alternatives to breastfeeding, universal named testing of pregnant women would provide an opportunity to advise more infected women not to breastfeed and might thereby reduce the number of vertically infected children. Since breastfeeding protects against infant deaths from infectious diseases, breastfeeding is still recommended where infectious diseases are a common cause of death in childhood, despite the additional risk of HIV transmission.

Acquired Immunodeficiency Syndrome

Methods for estimating the incidence of primary infection in pregnancy: a reappraisal of toxoplasmosis and cytomegalovirus data.

Accurate incidence information is required to plan and evaluate screening programmes which have been proposed for the detection of primary toxoplasmosis and cytomegalovirus infection in pregnancy. Appropriate statistical methods are described for deriving incidence rates and their confidence intervals from three types of data: change in age-specific seroprevalence, seroconversion, and IgM studies. These methods are applied to seven published studies on toxoplasmosis and cytomegalovirus carried out in the UK. In these publications only one estimate of the infection rate per pregnancy was correctly derived, and none were accompanied by confidence intervals. Using the proposed methods, most estimates of the primary toxoplasmosis rate in these studies were between 2.5 and 5.5 per 1000 pregnancies, compared to the 2 per 1000 usually cited. Most cytomegalovirus incidence estimates were between 4 and 10 per 1000 pregnancies.

Cytomegalovirus Infections

Two methods for assessing the risk-factor composition of the HIV-1 epidemic in heterosexual women: southeast England, 1988-1991.

OBJECTIVE: The prevalence of HIV-1 in the heterosexual population in southeast England between 1988 and 1991 was examined using two methods. DESIGN AND METHODS: First, district neonatal seroprevalence was compared on a geographical basis to social and demographic variables reflecting risk-factor prevalence. Second, over the same period eight children who developed AIDS within the first 12 months of life were born. RESULTS: The differences in seroprevalence between districts could be explained by the proportion of livebirths to women born in parts of Africa. An estimated 92% of neonatal seropositives could be associated with this demographic variable. The proportions of livebirths to women born in other countries, the prevalence of notified injecting drug use, and area measures of social deprivation, were only poorly related to HIV seroprevalence, and had no additional explanatory value. Seven of the eight (87.5%) children who developed AIDS in the first year were born to black women from Africa. CONCLUSIONS: Both methods suggest that a high proportion of heterosexually transmitted HIV in southeast England has been imported.

Adult

Cytomegalovirus prevalence in pregnant women: the influence of parity.

Over 20,000 women attending for antenatal care at three London hospitals were prospectively studied to determine the prevalence of cytomegalovirus (CMV) antibodies; 54.4% of these women were CMV seropositive. Ethnic group was strongly associated with CMV status: 45.9% of white women were seropositive, 88.2% of Asian, and 77.2% of black women (African/Caribbean ethnic origin). Among 12,159 white women born in the British Isles, seropositivity was independently associated with increasing parity, older age, lower social class, and being single at antenatal booking. The findings are consistent with the hypothesis that, in the UK, child to mother transmission of infection plays a significant part in the acquisition of CMV infection in adult life.

Africa

Evaluation of five commercial assays for screening antenatal sera for antibodies to Toxoplasma gondii.

AIMS: To evaluate the suitability of five commercial assays (Toxoreagent, DA, Captia Toxo IgG, Toxenz-G, Toxonostika-G) for screening large numbers of sera for antibodies to Toxoplasma gondii. METHODS: Sera from 1000 pregnant women booking for antenatal care at a London hospital were screened in parallel by each test. Sera giving discordant results were retested. RESULTS: The Captia Toxo IgG enzyme immune assay gave the best specificity on initial screening, with 0/773 false positives and only 2/218 false negatives. The Toxoreagent latex agglutination test performed well provided sera were tested at several dilutions to prevent prozone effects; 0/218 false negatives (greater than 12 IU/ml). Only one evidently false positive result was seen in the 1000 samples tested. The DA test gave no false negative results but produced 23/773 false positives. After repeat testing there were 9/1000 sera which gave equivocal results which were negative by the Captia Toxo IgG test (less than 12 IU/ml) but with low titres of 16 in the Toxoreagent test or 4 IU/ml in the DA test. In this situation women would have been asked for a follow up sample for repeat testing. Only 300 sera were tested by Toxenz-G; initial screening produced 4/58 false negative results and 4/242 false positives. CONCLUSIONS: The Captia Toxo IgG test gave the fewest discordant results on initial screening. Results could be readily expressed in international units using a programmable plate reader, and this may be useful for epidemiological studies. The Toxoreagent test is considerably cheaper, and is a simple and reliable method for screening provided that at least two dilutions are used.

Agglutination Tests

Plasma total thyroxine and free thyroxine concentrations in congenital hypothyroidism before and during treatment.

AIMS: To examine the relation between plasma total thyroxine and free thyroxine in children with congenital hypothyroidism. METHODS: Regression analysis was performed on 114 cases on the paired total thyroxine and free thyroxine measurements taken from the same blood sample. Conversion equations were derived using structural relation models. RESULTS: A linear relation was found between log total thyroxine and log free thyroxine values. The regression slopes for values taken before treatment and values taken while patients were receiving replacement treatment were significantly different. CONCLUSIONS: The data suggest that there is a close association between total and free thyroxine in congenital hypothyroidism, but that the relation is changed by thyroid replacement treatment.

Congenital Hypothyroidism

Prevalence of maternal HIV-1 infection in Thames regions: results from anonymous unlinked neonatal testing.

To monitor the spread of human immunodeficiency virus (HIV) in the heterosexual population, residues of blood samples collected routinely on absorbent paper for neonatal screening (Guthrie cards) in NE, NW, and SW Thames Regions in England have been tested for antibodies to HIV-1 since June, 1988. 323,369 dried blood spots were analysed to end March, 1991. Prevalence of anti-HIV-1 in newborn babies has remained stable in outer London and non-metropolitan districts whereas prevalence in inner London has increased from 1 in 2000 in the 12 months beginning June, 1988, to 1 in 500 in the first 3 months of 1991. Either exponential or linear growth in the numbers of new seropositives could account for the results. That obstetricians were aware of maternal HIV infection in only 20% of infected pregnancies, indicates the extent to which HIV infection goes unrecognised in the heterosexual community.

Confidentiality

Evaluating the sensitivity and predictive value of tests of recent infection: toxoplasmosis in pregnancy.

The diagnosis of maternal infection in early pregnancy depends on tests which are sensitive to recent infection, such as specific IgM. Two types of test are considered: those where the response persists for a period following infection and then declines, such as IgM, and those whose response increases with time since infection, such as IgG-avidity. However, individuals vary in their response to infection, and it may not always be possible to determine whether an infection occurred during pregnancy or before it. Mathematical methods are developed to evaluate the performance of these tests, and are applied to the diagnosis of toxoplasmosis in pregnancy. It is shown that, based on existing information, tests of recent infection are unlikely to be both sensitive and predictive. More data on these tests are required, before they can be reliably used to determine whether infection has occurred during pregnancy or before it.

Animals

Antigen detection, virus culture, polymerase chain reaction, and in vitro antibody production in the diagnosis of vertically transmitted HIV-1 infection.

Polymerase chain reaction (PCR), virus culture (V), antigen detection (Ag), and in vitro antibody production (IVAP) assays may be useful for the early detection of vertically transmitted HIV-1 infection in infants under 18 months of age, when a diagnosis cannot be based on seropositivity because of maternal antibody persistence. To assess the reliability of these procedures and to correlate diagnostic results with infection status, 101 children born to HIV-1-seropositive mothers were evaluated by all these techniques within the first 6 months of life. The children were then followed up to the age of at least 18 months, when diagnosis was made on the basis of AIDS or AIDS-related complex (ARC) onset or persistence of HIV-1 seropositivity. Out of 27 children classified as infected according to the above criteria, 25 (92.5%) were repeatedly positive in IVAP test, 22 (81.5%) in the first PCR analysis, and only 19 (70.3%) in the initial V assay. On further testing, a total of 24 children (88.9%) were found positive in PCR assay, and 23 (85.2%) in V test. All these assays were found to be more sensitive than antigen detection for HIV-1 infection diagnosis, but the antigenaemia was shown to be a useful prognostic marker of disease onset. We also found that both Ag and IVAP assays could give false-positive results in the first 2 months of life, which severely limits their diagnostic value during this period of time. False-positive results in PCR assay could occur at any time of the tested period and were unrelated to the child's age.(ABSTRACT TRUNCATED AT 250 WORDS)

Child, Preschool

Effect on intelligence of relaxing the low phenylalanine diet in phenylketonuria.

A total of 599 children with phenylketonuria, who had been treated early, were followed up prospectively in order to examine the association between intellectual progress from 4 to 14 years of age and control of phenylalanine concentrations. The phenylalanine rose from around 400 mumol/l during the first four years to above 900 mumol/l by 12 years. The children were divided into two cohorts: cohort I comprised 224 children born in the United Kingdom between 1964 and 1971 and cohort II 375 children born between 1972 and 1978. In a previous study it was shown that by 4 years of age these children already had a mean intelligence quotient (IQ) over half a standard deviation below general population norms, and that IQ fell linearly as average phenylalanine concentrations rose. Multiple regression was used to estimate the size of the associations between IQ at later ages and average phenylalanine concentrations in the periods between assessments, after controlling for previous IQ and phenylalanine control, social class, type of phenylketonuria, and factors relating to diagnosis and early management. For each 300 mumol/l rise in average phenylalanine concentrations for those aged 5 to 8 years IQ at 8 years fell by 4-6 points. This compared with a 7-10 point fall in IQ at 4 years for a similar rise in phenylalanine. After 8 years of age the association between IQ and phenylalanine control disappeared in cohort I but persisted in cohort II and was significant up to 10 years of age, although the association was smaller than at 8 years.

Adolescent

Prevalence of maternal HIV infection based on unlinked anonymous testing of newborn babies.

This pilot study established that unlinked anonymous testing of dried blood spots routinely collected on Guthrie cards for neonatal screening is a feasible method for monitoring HIV prevalence in women at the time of delivery. The method was sensitive, specific, and less expensive than more conventional ELISAs. 114,515 dried blood spots taken from cards collected in three Thames regions were tested for antibody to HIV-1. 28 samples were confirmed to be antibody positive by western blot (seroprevalence 0.24 per 1000). Unlinked anonymous screening of newborn babies should be extended to monitor the spread of HIV infection in the heterosexual population and to target preventive strategies and provision of health care.

Agglutination Tests

Diagnosis of human immunodeficiency virus 1 infection in infants: in vitro production of virus-specific antibody in lymphocytes.

In children born to mothers infected with human immunodeficiency virus 1 (HIV-1), a diagnosis of HIV infection cannot be based on a positive antibody result until at least 18 months of age. There is therefore an urgent need for simple and reliable methods of diagnosing HIV infection in these infants. The sensitivity and specificity of a test using the in vitro antibody production of HIV-specific IgG was assessed in children whose infection status was known and compared with virus and antigen detection. In vitro antibody production sensitivity was 90 to 95%, at least as sensitive as virus culture in antibody-positive infected children. In the first 2 months there is a relatively high proportion of false positive results, possibly a result of contamination by maternal cells. However, after this period in vitro antibody production is a simple, inexpensive and reliable tool for early diagnosis.

AIDS-Related Complex

Intelligence and quality of dietary treatment in phenylketonuria.

The records of the Phenylketonuria Register were examined to determine the factors associated with early intellectual progress in children who had received a diet low in phenylalanine from soon after birth. A total of 1031 children were born between 1964 and 1980 and started treatment before they were 4 months of age, and 808 of them were followed up prospectively. In 263 children born between 1964 and 1971 (cohort 1), the mean intelligence quotient (IQ) at 4 years rose with year of birth from 24 points below revised IQ norms to 10 points below; in 545 born between 1972 and 1980 (cohort 2) there was no further rise in IQ and the mean remained eight points below the norms. IQ fell progressively by roughly four points for each four weeks' delay in starting treatment, for each 300 mumol/l rise in mean phenylalanine concentrations during treatment, and for each five months during the first two years during which phenylalanine concentrations were below 120 mumol/l. Forty six children in cohort 2 had the most favourable treatment characteristics. Their mean IQ, after standardising for social class, was 112.6, and similar to the mean for the same group estimated by multiple regression, and to revised population IQ norms for the period during which the children were tested. The data suggest that many children who are treated early continue to suffer a mild degree of neurological impairment because of the difficulties in fully controlling the metabolic abnormality.

Child, Preschool

Antenatal testing for human immunodeficiency virus. Results from the Royal College of Obstetricians and Gynaecologists' National Study of HIV Infection in Pregnancy.

Current policies on antenatal testing for human immunodeficiency virus (HIV) in the main obstetric units of the United Kingdom and the Republic of Ireland were surveyed by postal questionnaire; 294 of 299 units responded. HIV testing was available at 192 (65%) of the 294 units that responded. 414 HIV-positive pregnancies in 386 women were reported from 74 (25%) units. Most were from Scotland, the four Thames Regions, and Ireland. In 46% of the HIV-positive women the infection was identified by antenatal testing; the remainder had been tested previously and knew that they were infected. The findings support the view that selective antenatal testing should be established in areas where no testing is offered at present and possibly that testing should be offered to all pregnant women in high-prevalence areas.

Counseling

Prevalence of antibodies to herpes simplex virus types 1 and 2 in pregnant women, and estimated rates of infection.

There has been a recent increase in notifications of genital herpes but it is not known whether this has been reflected in the pregnant population. We have therefore carried out a study to determine the prevalence of herpes simplex antibodies in pregnant women and to estimate the incidence of primary infection. Sera were collected from 3533 women at antenatal clinics and tested for total antibodies to herpes simples virus (HSV), and if positive, for specific antibodies to HSV-2. Estimates of HSV-1 seroprevalence were derived from the HSV-2 seronegative population. HSV-1 seroprevalence was nearly 100% in black women born in Africa or the Caribbean and 60-80% in white, Asian and UK born black women. It was lower in women in non-manual employment. HSV-2 seroprevalence was related to age, rising from 0 at age 16 to 40% at age 35 in black women, and to about 10% in Asian and white women. The estimated incidence of primary HSV-2 infection during pregnancy, per 1000 pregnancies, was about 2.4 in Asian women, 5 in white women, and 20 in black women. Estimates of the incidence of neonatal infection were derived from these figures and compared to the nationally reported rates.

Adult