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Understanding infectious disease dynamics and the effect on prevalence and incidence is crucial for public health policies. Disease incidence and prevalence are typically not observed directly and increasingly are estimated through the synthesis of indirect information from multiple data sources. We demonstrate how an evidence synthesis approach to the estimation of human immunodeficiency virus (HIV) prevalence in England and Wales can be extended to infer the underlying HIV incidence. Diverse time series of data can be used to obtain yearly "snapshots" (with associated uncertainty) of the proportion of the population in 4 compartments: not at risk, susceptible, HIV positive but undiagnosed, and diagnosed HIV positive. A multistate model for the infection and diagnosis processes is then formulated by expressing the changes in these proportions by a system of differential equations. By parameterizing incidence in terms of prevalence and contact rates, HIV transmission is further modeled. Use of additional data or prior information on demographics, risk behavior change and contact parameters allows simultaneous estimation of the transition rates, compartment prevalences, contact rates, and transmission probabilities.

Objective: To estimate trends in prevalence of HIV infection, undiagnosed and total, among adults aged 15-44 years in England and Wales since 2001., Design: Multiple surveillance systems and survey data are available to inform different aspects of the HIV epidemic in England and Wales. To coherently and consistently combine this information to estimate trends in HIV prevalence, we apply a multiparameter evidence synthesis in a Bayesian statistical framework., Methods: The study population is stratified by exposure group and region of residence. We synthesize data from behavioural and community surveys, unlinked anonymous seroprevalence surveys, and an annual survey of individuals with diagnosed HIV infection. Prevalence estimates are given with 95% credible intervals., Results: The estimated number of prevalent HIV infections in 15-44-year-olds has increased from 32,400 (29,600-35,900) in 2001 to 54,500 (50,500-59,100) in 2008, corresponding to an estimated prevalence of 1.5 per 1000 (1.4-1.7) rising to 2.4 per 1000 (2.3-2.6) in 2008. A rise in prevalence of diagnosed infection contributes substantially to the increase. There is no evidence of a statistically significant decrease in the prevalence of undiagnosed infection. The proportion of infections that are diagnosed has therefore also increased., Conclusion: Although the increase in the proportion of infections that are diagnosed is encouraging, the rise in HIV prevalence and lack of evidence of a decrease in prevalence of undiagnosed infection suggest that diagnosis rates are not high enough to reduce the pool of individuals unaware of their infection and that new infections must be occurring.

Decision models are usually populated 1 parameter at a time, with 1 item of information informing each parameter. Often, however, data may not be available on the parameters themselves but on several functions of parameters, and there may be more items of information than there are parameters to be estimated. The authors show how in these circumstances all the model parameters can be estimated simultaneously using Bayesian Markov chain Monte Carlo methods. Consistency of the information and/or the adequacy of the model can also be assessed within this framework. Statistical evidence synthesis using all available data should result in more precise estimates of parameters and functions of parameters, and is compatible with the emphasis currently placed on systematic use of evidence. To illustrate this, WinBUGS software is used to estimate a simple 9-parameter model of the epidemiology of HIV in women attending prenatal clinics, using information on 12 functions of parameters, and to thereby compute the expected net benefit of 2 alternative prenatal testing strategies, universal testing and targeted testing of high-risk groups. The authors demonstrate improved precision of estimates, and lower estimates of the expected value of perfect information, resulting from the use of all available data.

In the absence of interventions, 20% of infants born to women infected with HIV acquire infection from their mother at or before delivery. A further 15% are infected through breast feeding. Prenatal testing for HIV allows infected women to be reliably identified so that they can receive antiretroviral therapy and, in countries with safe water supplies, be advised not to breast feed. These and other interventions can reduce the risk of transmission to 5% or less. Economic evaluations of prenatal testing for HIV are reviewed and compared in this article, and future research priorities outlined. These studies set the costs of testing and intervention against the averted lifetime costs of paediatric infection, and generate estimates of the HIV prevalence threshold above which there would be a net cost saving, or calculate the cost per life-year saved given a particular prevalence. In the developed world, prenatal testing has been adopted in many countries, and recent economic analyses broadly support this. Future research is likely to focus on the incremental benefits of different antiretroviral regimens in lowering transmission rates still further, with or without elective caesarean section, and the possibility that some may lead to adverse effects in uninfected infants exposed to them in utero. Some earlier assessments in resource-poor settings concluded that prenatal testing was unaffordable or of doubtful cost effectiveness. This negative conclusion appears to be the result of very low estimates of the lifetime costs of paediatric HIV infection, together with developed world conceptions of pre-test counselling. The demonstration that nevirapine reduces transmission risk at a low cost has transformed the outlook, and there is hope that antiretrovirals can act prophylactically to prevent infection of the breast-fed child. However, to achieve a sustained reduction in vertical transmission there may be a need to evaluate the need for a strengthened infrastructure to deliver prenatal HIV testing and treatment, as well as programmes to reduce HIV incidence in adults.

Background: In order to monitor the epidemiology of human immunodeficiency virus (HIV), integrated national programmes of unlinked anonymous (blinded) HIV sero-surveys have taken place in the UK since 1990., Methods: The programmes comprise multi-centre surveys primarily using specimens gathered routinely for screening groups of patients. All specimens are irreversibly unlinked from patient identifiers before being tested., Results: The surveys have met their prime aim of providing at low cost minimally biased estimates of current HIV prevalence and trends in sentinel populations. The surveys have remained acceptable to professionals and the public, being successfully implemented without breech of their founding principles. The findings have had major public health applications, have influenced HIV policy and funding, been used for monitoring the spread of HIV, for targeting and evaluating health promotion and improving projections of severe HIV disease. The surveys have detected substantial prevalence rises and under-diagnosis of HIV which would otherwise have been unrecognised. The programmes' value is being increased by sub-typing HIV-1 isolates, capturing additional demographic information to detect spread among minority groups. The same specimens are used for monitoring other infections (initially hepatitis A, B and C)., Conclusions: Monitoring HIV and other infections through unlinked anonymous HIV surveillance has become an integral essential part of national HIV and AIDS surveillance. Although it has unique applications the value of unlinked anonymous surveillance is maximized when used in conjunction with behavioural data, information from HIV and AIDS reporting, and behavioural data and surveillance for other sexually transmitted infections.

Objective: To assess the cost effectiveness of universal antenatal HIV screening compared with selective screening in the United Kingdom., Design: Incremental cost effectiveness analysis relating additional costs of screening to life years gained. Maternal and paediatric costs and life years were combined., Setting: United Kingdom., Main Outcome Measures: Number of districts for which universal screening would be cost effective compared with selective screening under various conditions., Results: On base case assumptions, a new diagnosis of a pregnant woman with HIV results in a gain of 6.392 life years and additional expenditure of 14 833 pounds. If decision makers are prepared to pay up to 10 000 pounds an additional life year, this would imply a net benefit of 49 090 pounds (range 12 300 pounds- 59 000 pounds), which would be available to detect each additional infected woman in an antenatal screening programme. In London, universal antenatal screening would be cost effective compared with a selective screening under any reasonable assumptions about screening costs. Outside London, universal screening with uptake above 90% would be cost effective with a 0.60 pounds HIV antibody test cost and up to 3.5 minutes for pretest discussion. Cost effectiveness of universal testing is lower if selective testing can achieve high uptake among those at higher risk. A universal strategy with only 50% uptake may not be less cost effective in low prevalence districts and may cost more and be less effective than a well run selective strategy., Conclusions: Universal screening with pretest discussion should be adopted throughout the United Kingdom as part of routine antenatal care as long as test costs can be kept low and uptake high.

Objective: To estimate and interpret time trends in vertical transmission rates for HIV using data from national obstetric and paediatric surveillance registers., Design: Prospective study of HIV infected women reported through obstetric surveillance. HIV infection status of the child and onset of AIDS were reported through paediatric surveillance. Rates of vertical transmission and progression to AIDS rate were estimated by methods that take account of incomplete follow up of children with indeterminate infection status and delay in AIDS reporting., Setting: British Isles., Subjects: Pregnant women infected with HIV whose infection was diagnosed before delivery, and their babies., Main Outcome Measures: Mother to child transmission of infection and progression to AIDS in children., Results: By January 1999, 800 children born to diagnosed HIV infected women who had not breast fed had been reported. Vertical transmission rates rose to 19.6% (95% confidence interval 8. 0% to 32.5%) in 1993 before falling to 2.2% (0% to 7.8%) in 1998. Between 1995 and 1998 use of antiretroviral treatment increased significantly each year, reaching 97% of live births in 1998. The rate of elective caesarean section remained constant, at around 40%, up to 1997 but increased to 62% in 1998. Caesarean section and antiretroviral treatment together were estimated to reduce risk of transmission from 31.6% (13.6% to 52.2%) to 4.2% (0.8% to 8.5%). The proportion of infected children developing AIDS in the first 6 months fell from 17.7% (6.8% to 30.8%) before 1994 to 7.2% (0% to 15. 7%) after, coinciding with increased use of prophylaxis against Pneumocystis carinii pneumonia., Conclusions: In the British Isles both HIV related morbidity and vertical transmission are being reduced through increased use of interventions.

Objective: To assess the health service costs and benefits for the woman of an earlier HIV diagnosis as a result of antenatal HIV testing., Design: A model of maternal disease progression was developed based on the rate of decline in CD4 cell counts and applied to two matched simulated cohorts of women with identical initial CD4 cell levels and decline rates but whose HIV diagnosis occurred at different times as a result of antenatal HIV testing. UK data on CD4 cell count at HIV diagnosis and annual health service costs of care excluding antiretroviral therapy (ART) incurred at defined states of CD4 cell count were taken from published UK data. Costs of triple ART were added and effectiveness modelled by retarding the rate of CD4 cell count decline. Discounting costs at 6% and life-years at 2% per year, the additional costs per life-year gained by screening were calculated. Uncertainty was explored using sensitivity analysis., Results: Costs per life-year gained by antenatal diagnosis of women were pound sterling 51258 ($76887) assuming untested women were diagnosed a median of 20.4 months later than tested women, ART was initiated at a CD4 cell count of 350x10(6) cells/l and ART efficacy retarded decline in CD4 cell counts by 40% for life. Sensitivity analyses showed results were most sensitive to the assumed efficacy of lifetime ART and time assumed to HIV diagnosis for women not tested in pregnancy., Conclusion: This model provides a way of estimating the additional costs and benefits of future care for the woman resulting from an earlier HIV diagnosis through antenatal testing. These should be included with the paediatric costs averted and life-years gained from interventions to reduce mother-to-child transmission in order to evaluate the cost-effectiveness of antenatal screening in different populations and settings.

The objective was to assess the potential bias in unlinked anonymous HIV-seroprevalence surveys from objections to specimens being included. Objection rates in seroprevalence surveys were examined. Statistically large clusters of objections were considered to be the result of health care worker behaviour, and were disregarded. Underlying objection rates were estimated from remaining data and compared to seroprevalence. Overall objection rates approached or exceeded seroprevalence in many participating centres. However, underlying objection rates declined with time while prevalences were generally unchanging. Also, underlying rates correlated poorly with observed seroprevalences. Findings were therefore consistent with processes producing the clusters of objections and underlying objection rates independently of serostatus of individuals. Although national seroprevalence estimates produced by the surveys are reasonably free from objection bias, regional seroprevalence estimates outside London remain vulnerable to bias as a result of some centres returning data whose quality cannot be guaranteed.

Objective: To develop an epidemiological basis for economic analyses of selective and universal antenatal screening strategies, and to apply it to the UK., Methods: The prevalence of higher-risk women and the prevalence of undiagnosed infection within groups of high-risk and low-risk women was estimated from surveillance and survey data. The numbers of women tested and the numbers of infected women who would be identified by universal and selective strategies were then calculated under a range of assumptions about the identification of higher-risk women and acceptance of testing., Results: In higher-risk women estimated prevalence of undiagnosed infection was between 0.06% and 2.8%, comparing well with independent estimates. In low-risk women, estimates ranged from 0.014% in London to 0.002% in the rest of the UK. If uptake among the high-risk women was the same in selective and universal strategies, universal testing would entail testing between 7100 (London) and 50000 (rest of England) additional women to detect an additional case. However, if selective screening identified only 60% of those at high risk and achieved only 60% acceptance compared with a universal programme, then universal screening would require only 1150 additional women to identify one additional case in London, compared to 6470 in Scotland and 13140 in the rest of the UK., Conclusions: Overall prevalence does not form an adequate basis for determining screening strategy. Instead, universal screening can be justified either because the prevalence of HIV in the low-risk group is sufficiently high, or because it achieves sufficiently higher uptake relative to selective screening among those at higher risk.

Objectives: To examine the implications of variation in maternal infectivity on the timing of mother-to-child HIV transmission through breastfeeding., Design and Methods: A mathematical model of mother-to-child HIV transmission was developed that incorporates two main features: (i) the fetus/child potentially experiences a series of exposures (in utero, intrapartum, and via breastmilk) to HIV; and (ii) variation in maternal infectivity. The model was estimated from different sources of epidemiological data: a retrospective cohort study of children born to HIV-1-infected women in Sao Paulo State, Brazil, the International Registry of HIV-Exposed Twins, and the AIDS Clinical Trials Group 076 trial, which assessed the effectiveness of zidovudine in preventing mother-to-child HIV transmission., Results: Variation in maternal infectivity results in higher average risk of breastfeeding-related transmission in the early stages of breastfeeding than in the late stages, even in the absence of a direct relationship between transmission risk and the age of the child. However, the available data were unable to resolve the quantitative importance of this mechanism., Conclusions: Our model has helped identify a previously unrecognized determinant of the timing of breastfeeding-related HIV transmission, which may have adverse implications for the effectiveness of certain interventions to reduce mother-to-child HIV transmission such as maternal antiretroviral therapy in breastfeeding populations and the early cessation of breastfeeding.

An LMS-based maximum likelihood method of fitting age-related reference ranges is extended to incorporate non-independent measurements by including the matrix of the correlations between standard normalized repeat measurements into the likelihood. The likelihood is maximized via iterative re-estimation of the correlation structure and the reference range parameters until convergence is achieved. The correlation structure is explicitly modelled and the extent to which the estimated centiles depend on the adequacy with which the correlation structure is modelled is investigated. The method is illustrated using CD4 counts of uninfected children born to HIV-1 infected women. This data set consists of 5063 CD4 counts taken from 745 children at irregular ages between birth and 10 years of age. The data exhibited a strong correlation structure with correlations decreasing with increasing time between measurements and being lower for younger measurement ages. However, incorporation of the correlation had little effect on the choice of model for the median or on the fitted centiles or their precision.

Objective: To estimate the cost of managing children with HIV/AIDS in the UK from a health service perspective., Design and Methods: Epidemiological, resource use and unit cost data were combined within a decision analytic model. A Markov model was developed to predict the prognoses of HIV-infected children under different assumptions about natural history, treatment efficacy and the timing of antiretroviral therapy. Resource use estimates for various stages of HIV/AIDS were based on published data relating to the UK health service and clinical judgement; unit cost data were taken from a London centre., Results: The base-case results suggest that the cost of caring for an HIV-infected child is higher if the mother's infection was known about at or before the child's birth (antenatal screened cohort): lifetime costs ranged from 46 427 pound sterling to 119 502 pound sterling per child in the screened cohort and from 38 691 pound sterling to 86 014 pound sterling in the unscreened cohort. However, the screened cohort benefited from longer life expectancy (base-case, 11.66 versus 10.09 years) and AIDS-free life expectancy (base-case, 7.13 years versus 6.22 years). Results are sensitive to assumptions about natural history and treatment efficacy: for example, if antiretroviral therapy was initiated at birth, and assuming optimistic natural history parameters, discounted costs could increase to 215 077 pound sterling and the additional lifetime cost of a child born to a screened mother could be 72 491 pound sterling., Conclusions: Results reflect the marked uncertainty regarding the cost of, and prognosis for, children with HIV/AIDS in the new era of more potent antiretroviral combination therapies. These results are part of an assessment of the relative cost-effectiveness of alternative antenatal HIV testing strategies.

Objective: To estimate the cost-effectiveness of alternative interventions to reduce the risk of mother-to-child transmission of HIV., Design: A model capturing the sequential nature of mother-to-child transmission in utero, at delivery and postnatally was used to determine how the effects of bottle-feeding, elective Cesarean section (CS) and zidovudine (ZDV) would combine to prevent mother-to-child HIV transmission. Parameter estimates were derived from the literature, UK health service costs applied, and incremental cost effectiveness ratios (ICER) estimated for alternative risk reduction strategies. Results can be transposed to other cost assumptions or currencies., Results: In a woman who breast-feeds her baby, has a vaginal or emergency CS delivery and takes no ZDV, the estimated transmission risk is 31.6% (range, 23.7-38.1%), at a cost of 400 UK pound per woman; this falls to a risk of 3.7% (range, 1.7-6.9%) when bottle-feeding, ZDV therapy and elective CS are all implemented at a cost of 1968 UK pound per woman. From a public health perspective the ICER of ZDV and elective CS each depend on the acceptance rates of the other. In women counselled against breast-feeding, ZDV with 100% acceptance of elective CS has an ICER of 11 342 UK pound (95% confidence interval (CI), 7084-21 515 UK pound]. However, the ICER of CS ranges from 9248 UK pound (95% CI, 5072-46 913 pound sterling) at zero ZDV acceptance to 27 895 UK pound (95% CI, 10 018-154 462 pound sterling) at 100% ZDV acceptance., Conclusions: Considering the estimated cost of caring for an infected child, ZDV appears to be cost-effective under any of the circumstances examined. However, elective CS may not be cost-effective in populations where the uptake of ZDV is high, and a more precise estimate of its efficacy is required.

Background: Hepatitis C virus (HCV) vertical transmission studies have reported conflicting findings, possibly due to differences in HCV transmission risk factors among maternal populations, or to methodological differences., Methods: Systematic review of worldwide published and unpublished HCV vertical transmission studies. Standardized diagnostic criteria were applied to minimize methodological differences, and transmission rates recalculated according to maternal HCV viraemic and human immunodeficiency virus (HIV) infection status., Results: In all, 976 eligible infants from 28 studies were followed up sufficiently for recalculation of transmission rates. Overall transmission rates were less than 10% in 8/12 studies of HIV negative mothers, compared with 2/7 studies comprising at least 50% HIV-coinfected mothers. Rates from 409 viraemic mothers in 15 studies ranged from 0% to 41%, being less than 10% from HIV negative mothers in 6/13 studies and from HIV positive mothers in 1/6 studies. Nine studies measured maternal viraemia levels, with only 2/30 transmitting mothers having < 10(6) copies/ml of HCV RNA. Eight transmissions were identified overall from non-viraemic mothers. Significant transmission rate variation remained after accounting for maternal viraemia and HIV coinfection, possibly due to differences in other vertical transmission risk factors, in frequencies of postnatal transmission, or residual differences in study methodologies., Conclusions: Overall, HCV transmission is largely restricted to infants born to HCV viraemic mothers, and low risks among most HIV negative mothers may be due to lower HCV viraemia levels. International agreement on standardized diagnostic criteria for HCV vertical transmission would facilitate pooling of individual findings, to allow more precise transmission estimates and further investigation of risk factors.

Objectives: To measure the uptake of antenatal HIV testing and determine its relation to risk of HIV and to screening practices., Design: Multicentre prospective questionnaire study., Subjects: Pregnant women attending six maternity units., Setting: Inner London, 1995-6., Main Outcome Measures: Uptake of testing by risk factors for HIV, ethnicity, and factors about the antenatal interview., Results: All units had a "universal offer" policy for HIV testing. In five units forms were completed for 18,791 (88%) of 21,247 pregnant women. The sixth unit, where the response rate was too low to assess uptake, was excluded from the analysis. Uptake ranged from 3.4% to 51.2% (overall 22.9%), in parallel with detection of previously undiagnosed infection in pregnant women (4.9-60%). Controlling for unit, uptake was higher among the 7% who disclosed risk factors. Among those at low risk, uptake varied by ethnic group (South Asian women 9%; Latin American and Mediterranean women 33%). The relation between uptake and HIV risk category varied greatly across units. Despite increased HIV seroprevalence in black African women, uptake was similar in this group to that among women at low risk (24%). Uptake increased 2.1-fold if HIV transmission was discussed. Midwives reported spending 7 (2-15) minutes discussing HIV issues., Conclusions: Uptake of HIV testing was unacceptably low in all units, with maternity unit the strongest predictor. New approaches to antenatal HIV testing are urgently required and uptake should be audited routinely.

Objective: To describe the epidemiology of HIV-1 infection in pregnant women in the United Kingdom., Design: Serial unlinked serosurveillance for HIV-1 in neonatal specimens and surveillance through registers of diagnosed maternal and paediatric infections from reporting by obstetricians, paediatricians, and microbiologists., Setting: United Kingdom, 1988-96., Subjects: Pregnant women proceeding to live births and their children., Main Outcome Measures: Time trends in prevalence of HIV-1 seropositivity in newborn infants (as a proxy for infection in mothers); the proportions of mothers with diagnosed HIV-1 infections, and their characteristics., Results: HIV-1 prevalence among mothers in London rose sixfold between 1988 and 1996 (0.19% of women tested; 1 in 520 in 1996). Apart from in Edinburgh and Dundee, levels remained low in Scotland (0.025%; 1 in 3970) and elsewhere in the United Kingdom (0.016%; 1 in 1930). Over a third of births to infected mothers in 1996 occurred outside London. In London the reported infections were predominantly among black African women, whereas in Scotland most were associated with drug injecting. The contribution of reported infection among African women increased over time as that of drug injecting declined. In Scotland 51% of mothers' infections were diagnosed before the birth. In England, despite a national policy initiative in 1992 to increase the antenatal detection rate of HIV, no improvement in detection was observed, and in 1996 only 15% of previously unrecognised HIV infections were diagnosed during pregnancy., Conclusions: HIV-1 infection affects mothers throughout the United Kingdom but is most common in London. Levels of diagnosis in pregnant women have not improved. Surveillance data can monitor effectively the impact of initiatives to reduce preventable HIV-1 infections in children.

Background: In 1996 only 13.5% of previously undiagnosed HIV infected women were detected in pregnancy. In this study, all 265 maternity units in the United Kingdom were surveyed to determine the relation between screening strategy, uptake of testing, and detection rate., Methods: Data on HIV screening strategy and uptake of testing were collected in 1997 by postal questionnaire. The proportion of women with previously undiagnosed HIV infection identified during pregnancy (detection rate) was calculated using data from national obstetric HIV surveillance and unlinked anonymous seroprevalence studies., Results: 239 (90%) units responded; 25 of these (10%) had a universal offer strategy, 89 (37%) a selective offer, and 125 (52%) tested only women who requested it. All selective units offered testing to injecting drug users, but only 26% to women who had lived abroad in high prevalence areas. Uptake was over 10% in only eight units, all with a universal strategy, and in 76% of selective units it was below 0.1%. The detection rate was 14.7% in universal units, 7.8% in selective units, and 7.7% in on request units. In universal units, detection increased by 6.3% (95% confidence interval 3.7% to 8.8%) for every 10% increase in uptake of testing. There was evidence of both selective presentation for testing and avoidance of testing among infected women., Conclusions: All current antenatal HIV testing strategies fail to identify most infected women. Universal offer strategies achieve a very low uptake and a poor detection rate. Units with selective strategies tend to test only a minority of women at high risk and do not target all the main high risk groups.

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.

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.

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.

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.

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.

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.

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.

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)

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.

Planning, implementation and evaluation of public health policies to control the human immunodeficiency virus (HIV) epidemic require regular monitoring of disease burden. This includes the proportion living with HIV, whether diagnosed or not, and the rate of new infections in the general population and in specific risk groups and regions. Estimation of these quantities is not straightforward: data informing them directly are not typically available, but a wealth of indirect information from surveillance systems and ad hoc studies can inform functions of these quantities. In this paper we show how the estimation problem can be successfully solved through a Bayesian evidence synthesis approach, relaxing the focus on "best available" data to which classical methods are typically restricted. This more comprehensive and flexible use of evidence has led to the adoption of our proposed approach as the official method to estimate HIV prevalence in the United Kingdom since 2005. [ABSTRACT FROM AUTHOR]

Presents a study of human retroviruses human T-lymphotropic virus (HTLV) seroprevalence among pregnant women in Europe. Determination of the maternal antibody status of pregnant women; Details on the epidemiology of HTLV infections; Evidence of spreading HIV infections.