Cutaneous manifestations induced by check point inhibitors in 120 melanoma patients-The European MelSkinTox study.

BACKGROUND: Checkpoint inhibitors provide an effective approach for the melanoma treatment. They prolong lymphocyte effects, which explains the cytotoxicity underlying immune-related adverse events (IrAEs). Cutaneous IrAEs affect nearly 40% of PD-1i and 50% of CTLA4i-treated patients. Severe cutaneous irAE do not often occur but could be life-threatening and may persist despite treatment discontinuation. METHODS: We aimed to investigate cutaneous IrAEs in a cohort of patients treated with ICI across Europe in an effort to characterize the reactions in a real-world, phase IV, post-marketing study using a follow-up questionnaire. Data since November 2016 until March 2021 were obtained from the Melskintox database, a European multicentric biobank dedicated to the follow-up of melanoma and cutaneous adverse events, supported by EADO. The dermatoses reported were pooled into four categories: inflammatory dermatosis, bullous diseases, drug-related eruptions and pigmentary diseases. RESULTS: Inflammatory benign dermatoses (n = 63) represented the most common group of reactions (52.5%), followed by drug-related eruptions (n = 24, 20%), pigmentary diseases (n = 23, 19.2%) and bullous diseases (n = 10, 8.3%). Grade II (n = 41, 34.2%) are represented by bullous pemphigoid, eczema, hypodermitis, lichenoid eruption, maculopapular rash, pruritus, psoriasis-like rash, urticarial eruption and vitiligo. Grade III (n = 18, 15.0%) are represented by bullous pemphigoid, lichenoid eruption and rashes. Grade IV (n = 2, 1.7%) is only represented by bullous disease. Most cutaneous IrAEs led to immunotherapy continuation (n = 95, 88.0%). CR is associated with more severe the cutaneous irAEs. We report an average time-to-onset of 208 days and some late-onset events. CONCLUSION: Our study has characterized the clinical spectrum of cutaneous irAEs, their timing and severity and their relationship with tumour response. Grade I-II cutaneous IrAE are easily managed allowing ongoing anticancer treatment. Severe late-onset cutaneous irAE are not uncommon. A dermatological follow-up helps mitigate the risk of life-threatening adverse events. These findings highlight the importance of oncodermatological involvement in management of patients with melanoma receiving immunotherapy.

National audit of perinatal HIV infections in the UK, 2006-2013: what lessons can be learnt?

OBJECTIVES: The aim of the study was to investigate circumstances surrounding perinatal transmissions of HIV (PHIVs) in the UK. METHODS: The National Study of HIV in Pregnancy and Childhood conducts comprehensive surveillance of all pregnancies in women diagnosed with HIV infection and their infants in the UK; reports of all HIV-diagnosed children are also sought, regardless of country of birth. Children with PHIV born in 2006-2013 and reported by 2014 were included in an audit, with additional data collection via telephone interviews with clinicians involved in each case. Contributing factors for each transmission were identified, and cases described according to main likely contributing factor, by maternal diagnosis timing. RESULTS: A total of 108 PHIVs were identified. Of the 41 (38%) infants whose mothers were diagnosed before delivery, it is probable that most were infected in utero, around 20% intrapartum and 20% through breastfeeding. Timing of transmission was unknown for most children of undiagnosed mothers. For infants born to diagnosed women, the most common contributing factors for transmission were difficulties with engagement and/or antiretroviral therapy (ART) adherence in pregnancy (14 of 41) and late antenatal booking (nine of 41); for the 67 children with undiagnosed mothers, these were decline of HIV testing (28 of 67) and seroconversion (23 of 67). Adverse social circumstances around the time of pregnancy were reported for 53% of women, including uncertain immigration status, housing problems and intimate partner violence. Eight children died, all born to undiagnosed mothers. CONCLUSIONS: Priority areas requiring improvement include reducing incident infections, improving ART adherence and facilitating better engagement in care, with attention to addressing the health inequalities and adverse social situations faced by these women.

UK national clinical audit: management of pregnancies in women with HIV.

BACKGROUND: The potential for HIV transmission between a pregnant woman and her unborn child was first recognized in 1982. Since then a complex package of measures to reduce risk has been developed. This project aims to review UK management of HIV in pregnancy as part of the British HIV Association (BHIVA) audit programme. METHODS: The National Study of HIV in Pregnancy and Childhood (NSHPC), a population-based surveillance study, provided data for pregnancies with an expected delivery date from 1/1/13 - 30/6/14. Services also completed a survey on local management policies. Data were audited against the 2012 BHIVA pregnancy guidelines. RESULTS: During the audit period 1483 pregnancies were reported and 112 services completed the survey. Use of dedicated multidisciplinary teams was reported by 99% although 26% included neither a specialist midwife nor nurse. 17% of services reported delays >1 week for HIV specialist review of women diagnosed antenatally. Problematic urgent HIV testing had been experienced by 9% of services although in a further 49% the need for urgent testing had not arisen. Delays of >2 h in obtaining urgent results were common. Antiretroviral therapy (ART) was started during pregnancy in 37% women with >94% regimens in accordance with guidelines. Late ART initiation was common, particularly in those with a low CD4 count or high viral load. Eleven percent of services reported local policy contrary to guidelines regarding delivery mode for women with a VL <50 copies/mL at ≥36 weeks. According to NSHPC reports 27% of women virologically eligible for vaginal delivery planned to deliver by CS. CONCLUSIONS: Pregnant women in the UK are managed largely in accordance with BHIVA guidelines. Improvements are needed to ensure timely referral and ART initiation to ensure the best possible outcomes.

The incidence of congenital syphilis in the United Kingdom: February 2010 to January 2015.

OBJECTIVE: To estimate the incidence of congenital syphilis in the UK. DESIGN: Prospective study. SETTING AND POPULATION: United Kingdom. METHODS: Children born between February 2010 and January 2015 with a suspected diagnosis of congenital syphilis were reported through an active surveillance system. MAIN OUTCOME MEASURES: Number of congenital syphilis cases and incidence. RESULTS: For all years, reported incidence was below the WHO threshold for elimination (<0.5/1000 live births). Seventeen cases (12 male, five female) were identified. About 50% of infants (8/17) were born preterm (<37 weeks' gestation): median birthweight 2000 g (865-3170 g). Clinical presentation varied from asymptomatic to acute disease, including severe anaemia, hepatosplenomegaly, rhinitis, thrombocytopaenia, skeletal damage, and neurosyphilis. One infant was deaf and blind. Median maternal age was 20 years (17-31) at delivery. Where maternal stage of infection was recorded, 6/10 had primary, 3/10 secondary and 1/10 early latent syphilis. Most mothers were white (13/16). Country of birth was recorded for 12 mothers: UK (n = 6), Eastern Europe (n = 3), Middle East (n = 1), and South East Asia (n = 2). The social circumstances of mothers varied and included drug use and sex work. Some experienced difficulty accessing health care. CONCLUSION: The incidence of congenital syphilis is controlled and monitored by healthcare services and related surveillance systems, and is now below the WHO elimination threshold. However, reducing the public health impact of this preventable disease in the UK is highly dependent on the successful implementation of WHO elimination standards across Europe. TWEETABLE ABSTRACT: Congenital syphilis incidence in the UK is at a very low level and well below the WHO elimination threshold.

Syphilis screening in pregnancy in the United Kingdom, 2010-2011: a national surveillance study.

OBJECTIVE: To evaluate the national antenatal syphilis screening programme and provide evidence for improving screening and management strategies. DESIGN: National population-based surveillance. SETTING: United Kingdom (UK). POPULATION: All pregnant women screening positive for syphilis, 2010-2011. METHODS: Demographic, laboratory and treatment details for each pregnancy were collected from UK antenatal units (~210), along with follow-up information on all infants born to women requiring syphilis treatment in pregnancy. MAIN OUTCOME MEASURES: Proportion of women with newly or previously diagnosed syphilis among those with positive screening tests in pregnancy; proportion requiring treatment. RESULTS: Overall, 77% (1425/1840) of reported pregnancies were confirmed syphilis screen-positive. Of these, 71% (1010/1425) were in women with previously diagnosed syphilis (155 requiring treatment), 26% (374/1425) with newly diagnosed syphilis (all requiring treatment) and 3% (41/1425) required treatment but the reason for treatment was unclear. Thus 40% (570/1425) required treatment overall; of these, 96% (516/537) were treated (missing data: 33/570), although for 18% (83/456), this was not until the third trimester (missing data: 60/537). Follow up of infants born to treated women was poor, with at least a third not followed. Six infants were diagnosed with congenital syphilis; two mothers were untreated, three had delayed treatment and one had incomplete treatment (first trimester). CONCLUSION: Over 2 years, among pregnant women with confirmed positive syphilis screening results in the UK, a quarter had newly diagnosed infections and 40% required treatment. Despite high uptake of treatment, antenatal syphilis management could be improved by earlier detection, earlier treatment, and stronger links between healthcare teams. TWEETABLE ABSTRACT: 25% of pregnant women screening positive for syphilis in the UK were newly diagnosed and 40% needed treatment.

Pregnancies in older women living with HIV in the UK and Ireland.

OBJECTIVES: The aim of the study was to compare maternal characteristics and pregnancy outcomes in women aged < 40 years and ≥ 40 years in a large unselected population of HIV-positive women delivering in the UK and Ireland between 2000 and 2014. METHODS: Comprehensive population-based surveillance data on all HIV-positive pregnant women and their children seen for care in the UK and Ireland are collected through the National Study of HIV in Pregnancy and Childhood. All singleton and multiple pregnancies reported by the end of June 2015 resulting in live birth or stillbirth to women diagnosed with HIV infection before delivery and delivering in 2000-2014 were included. Logistic regression models were fitted in analyses examining the association between older maternal age and specific outcomes (preterm delivery and stillbirth). RESULTS: Among 15 501 pregnancies in HIV-positive women, the proportion in older women (≥ 40 years) increased from 2.1% (73 of 3419) in 2000-2004 to 8.9% (510 of 5748) in 2010-2014 (P < 0.001). Compared with pregnancies in younger women, those in older women were more likely to result in multiple birth (3.0 vs. 1.9% in younger women; P = 0.03), stillbirth (adjusted odds ratio 2.39; P = 0.004) or an infant with a chromosomal abnormality (1.6 vs. 0.2%, respectively; P < 0.001). However, there was no increased risk of preterm delivery, low birth weight or mother-to-child HIV transmission among older mothers. CONCLUSIONS: There has been a significant increase over time in the proportion of deliveries to women living with HIV aged ≥ 40 years, which has implications for pregnancy management, given their increased risk of multiple births, stillbirth and chromosomal anomalies, as also apparent in the general population.

Presentation for care and antenatal management of HIV in the UK, 2009-2014.

OBJECTIVES: Despite very low rates of vertical transmission of HIV in the UK overall, rates are higher among women starting antenatal antiretroviral therapy (ART) late. We investigated the timing of key elements of the care of HIV-positive pregnant women [antenatal care booking, HIV laboratory assessment (CD4 count and HIV viral load) and antenatal ART initiation], to assess whether clinical practice is changing in line with recommendations, and to investigate factors associated with delayed care. METHODS: We used the UK's National Study of HIV in Pregnancy and Childhood for 2009-2014. Data were analysed by fitting logistic regression and Cox proportional hazards models. RESULTS: A total of 5693 births were reported; 79.5% were in women diagnosed with HIV prior to that pregnancy. Median gestation at antenatal booking was 12.1 weeks [interquartile range (IQR) 10.0-15.6 weeks] and booking was significantly earlier during 2012-2014 vs. 2009-2011 (P < 0.001), although only in previously diagnosed women. Overall, 42.2% of pregnancies were booked late (≥ 13 gestational weeks). Among women not already on treatment, antenatal ART commenced at a median of 21.4 (IQR18.1-24.5) weeks and started significantly earlier in the most recent time period (P < 0.001). Compared with previously diagnosed women, those newly diagnosed during the current pregnancy booked later for antenatal care and started antenatal ART later (both P < 0.001). Multivariable analyses revealed demographic variations in access to or uptake of care, with groups including migrants and parous women initiating care later. CONCLUSIONS: Although women are accessing antenatal and HIV care earlier in pregnancy, some continue to face barriers to timely initiation of antenatal care and ART.

Duration of ruptured membranes and mother-to-child HIV transmission: a prospective population-based surveillance study.

OBJECTIVE: To investigate the association between duration of rupture of membranes (ROM) and mother-to-child HIV transmission (MTCT) rates in the era of combination antiretroviral therapy (cART). DESIGN: The National Study of HIV in Pregnancy and Childhood (NSHPC) undertakes comprehensive population-based surveillance of HIV in pregnant women and children. SETTING: UK and Ireland. POPULATION: A cohort of 2398 singleton pregnancies delivered vaginally, or by emergency caesarean section, in women on cART in pregnancy during the period 2007-2012 with information on duration of ROM; HIV infection status was available for 1898 infants. METHODS: Descriptive analysis of NSHPC data. MAIN OUTCOME MEASURES: Rates of MTCT. RESULTS: In 2116 pregnancies delivered at term, the median duration of ROM was 3 hours 30 minutes (interquartile range, IQR 1-8 hours). The overall MTCT rate for women delivering at term with duration of ROM ≥4 hours was 0.64% compared with 0.34% for ROM <4 hours, with no significant difference between the groups (OR 1.90, 95% CI 0.45-7.97). In women delivering at term with a viral load of <50 copies/ml, there was no evidence of a difference in MTCT rates with duration of ROM ≥4 hours, compared with <4 hours (0.14% for ≥4 hours versus 0.12% for <4 hour; OR 1.14, 95% CI 0.07-18.27). Among infants born preterm with infection status available, there were no transmissions in 163 deliveries where the maternal viral load was <50 copies/ml. CONCLUSIONS: No association was found between duration of ROM and MTCT in women taking cART. TWEETABLE ABSTRACT: Rupture of membranes of more than 4 hours is not associated with MTCT of HIV in women on effective ART delivering at term.

British HIV Association guidelines for the management of HIV infection in pregnant women 2012.

The overall purpose of these guidelines is to provide guidance on best clinical practice in the treatment and management of human immunodeficiency virus (HIV)-positive pregnant women in the UK. The scope includes guidance on the use of antiretroviral therapy (ART) both to prevent HIV mother-to-child transmission (MTCT) and for the welfare of the mother herself, guidance on mode of delivery and recommendations in specific patient populations where other factors need to be taken into consideration,such as coinfection with other agents. The guidelines are aimed at clinical professionals directly involved with, and responsible for, the care of pregnant women with HIV infection.

Pregnancy outcomes in adolescents in the UK and Ireland growing up with HIV.

OBJECTIVES: Adolescents with HIV infection acquired perinatally or in early childhood are becoming sexually active, but little is known about fertility and pregnancy outcomes. Multicentre data on pregnancy outcomes in this population are described here. METHODS: A retrospective case note review of pregnant women with perinatal/early acquired HIV infection, conceiving before 1 September 2009 and attending participating centres in the UK and Ireland, was carried out. RESULTS: Among 252 women with perinatal/early acquired infection aged 12 years and older under follow-up in 21 centres, 42 pregnancies were reported in 30 women (19 women with a single pregnancy, 10 women with two pregnancies, and one woman with three pregnancies). Fifteen women (50%) had previous AIDS-defining diagnoses. The median age at first reported pregnancy was 18 years (range 14-22 years). Of the 42 pregnancies, 34 (81%) were reportedly unplanned, 31 (74%) involved regular partners, and in 21 (50%) of the 42 pregnancies the partners were reported to be unaware of maternal HIV status. Fifteen of the 42 pregnancies (36%) were electively terminated, six of the 42 (14%) resulted in first-trimester miscarriages and 21 of the 42 (50%) resulted in live births. Maternal viral load was detectable close to delivery in seven of 21 pregnancies (33%). Four infants required neonatal intensive care, three of whom were delivered preterm. One infant is HIV infected, there are ongoing concerns about the development of three of 21 infants (14%), and two of 21 (10%) have been fostered. CONCLUSIONS: Despite access to ongoing sexual health and contraceptive services, unplanned pregnancies are occurring in young women growing up with HIV. Pregnancy care and prevention of onward transmission require complex case management for this emerging population.

British HIV Association and Children's HIV Association position statement on infant feeding in the UK 2011.

To prevent the transmission of HIV infection during the postpartum period, the British HIV Association and Children's HIV Association (BHIVA/CHIVA) continue to recommend the complete avoidance of breast feeding for infants born to HIV-infected mothers, regardless of maternal disease status, viral load or treatment.

Antiretroviral therapy and preterm delivery-a pooled analysis of data from the United States and Europe.

OBJECTIVE: To investigate reported differences in the association between highly active antiretroviral therapy (HAART) in pregnancy and the risk of preterm delivery among HIV-infected women. DESIGN: Combined analysis of data from three observational studies. SETTING: USA and Europe. POPULATION: A total of 19, 585 singleton infants born to HIV-infected women, 1990-2006. METHODS: Data from the Pediatric Spectrum of HIV Disease project (PSD), a US monitoring study, the European Collaborative Study (ECS), a consented cohort study, and the National Study of HIV in Pregnancy and Childhood (NSHPC), the United Kingdom and Ireland surveillance study. MAIN OUTCOME MEASURE: Preterm delivery rate (<37 weeks of gestation). RESULTS: Compared with monotherapy, HAART was associated with increased preterm delivery risk in the ECS (adjusted odds ratio [AOR] 2.40, 95% CI 1.49-3.86) and NSHPC (AOR 1.43, 95% CI 1.10-1.86), but not in the PSD (AOR 0.92, 95% CI 0.67-1.26), after adjusting for relevant covariates. Because of heterogeneity, data were not pooled for this comparison, but heterogeneity disappeared when HAART was compared with dual therapy (P = 0.26). In a pooled analysis, HAART was associated with 1.5-fold increased odds of preterm delivery compared with dual therapy (95% CI 1.19-1.87, P=0.001), after adjusting for covariates. CONCLUSIONS: Heterogeneity in the association between HAART and preterm delivery was not explained by study design, adjustment for confounders or a standard analytical approach, but may have been the result of substantial differences in populations and data collected. The pooled analysis comparing HAART with dual therapy showed an increased risk of preterm delivery associated with HAART.

Discordance between CD4 cell count and CD4 cell percentage: implications for when to start antiretroviral therapy in HIV-1 infected children.

OBJECTIVE: Antiretroviral therapy (ART) guidelines for HIV-1-infected children specify both absolute CD4 cell count and CD4 percentage thresholds at which consideration should be given to initiating ART. This leads to clinical dilemma when one marker is below the threshold, whereas the other is above. DESIGN: Data were obtained on a large group of children followed longitudinally in trials and cohort studies in Europe and the USA. Follow-up was censored 6 months after the start of any antiretroviral drug other than zidovudine monotherapy. METHODS: Discordance between CD4 cell count and percentage was defined in relation to ART initiation thresholds in World Health Organization (WHO) and European paediatric treatment guidelines. The relative prognostic value of CD4 cell count and percentage for progression to AIDS/death was investigated using time-updated Cox proportional hazards models, stratified by age. RESULTS: Among 3345 children, with a total of 21,815 pairs of CD4 measurements analysed, 980 developed AIDS and/or died after a median follow-up of 1.7 years. Over one-half of children had discordant values of CD4 cell markers at the first visit when one or both treatment thresholds were crossed and approximately one-third had the same pattern of discordance at a subsequent measurement. Models suggested that CD4 percentage had little or no prognostic value over and above that contained in CD4 cell count, irrespective of age. CONCLUSIONS: More emphasis should be placed on CD4 cell count than on CD4 percentage in deciding when to start ART in HIV-1-infected children.

Rubella seroprevalence in pregnant women in North Thames: estimates based on newborn screening samples.

OBJECTIVES: Routine screening for rubella susceptibility is recommended in the UK so that women found to be susceptible can be offered immunization in the post partum period. We demonstrate the use of newborn dried blood spot samples linked to routine vital statistics datasets to monitor rubella susceptibility in pregnant women and to investigate maternal characteristics as determinants of rubella seronegativity. SETTING: North Thames region of England (including large parts of inner London). METHODS: Maternally acquired rubella IgG antibody levels were measured in 18882 newborn screening blood spot samples. Latent class regression finite mixture models were used to classify samples as seronegative to rubella. Data on maternal country of birth were available through linkage to birth registration data. RESULTS: An estimated 2.7% (95% CI 2.4%-3.0%) of newly delivered women in North Thames were found to be seronegative. Mothers born abroad, particularly in Sub-Saharan Africa and South Asia, were more likely to be seronegative than UK-born mothers, with adjusted odds ratios of 4.2 (95% CI 3.1-5.6) and 5.0 (3.8-6.5), respectively. Mothers under 20 years were more likely to be seronegative than those aged 30 to 34. CONCLUSION: Our findings highlight the need for vaccination to be targeted specifically at migrant women and their families to ensure that they are protected from rubella in pregnancy and its serious consequences.

Vertically acquired HIV diagnosed in adolescence and early adulthood in the United Kingdom and Ireland: findings from national surveillance.

OBJECTIVE: The aim of the study was to describe the characteristics of young people with vertically acquired HIV diagnosed aged > or =13 years. METHODS: A retrospective review of HIV diagnoses reported to well-established national paediatric and adult HIV surveillance systems in the United Kingdom/Ireland was conducted. RESULTS: Forty-two young people with vertically acquired HIV diagnosed aged > or =13 years were identified; 23 (55%) were female, 40 (95%) were black African and 36 (86%) were born in sub-Saharan Africa. The median age at HIV diagnosis was 14 years (range, 13-20 years). Half of the patients presented with symptoms; the remainder were screened for HIV following diagnosis of a relative. The median CD4 count at diagnosis was 210 cells/microL (range, 0-689 cells/microL), 12 patients (29%) were diagnosed with AIDS at HIV diagnosis or subsequently, and 34 (81%) started combination antiretroviral therapy (ART), most (31 of 34) within a year of diagnosis. CONCLUSION: A small number of young people with vertically acquired HIV survive childhood without ART and are diagnosed at age > or =13 years in the United Kingdom/Ireland. Half of the patients were asymptomatic, highlighting the importance of considering HIV testing for all offspring of HIV-infected women, regardless of age or symptoms. Increased awareness among clinicians and parents is required to reduce delayed presentation with advanced disease and to avoid onward transmission as these young people become sexually active.

Trends in management and outcome of pregnancies in HIV-infected women in the UK and Ireland, 1990-2006.

OBJECTIVE: To describe the changing demographic profile of diagnosed HIV-infected pregnant women over time and trends in pregnancy outcome, uptake of interventions and mother-to-child transmission. DESIGN: National surveillance study. SETTING: UK and Ireland. POPULATION: Diagnosed HIV-infected pregnant women, 1990-2006. METHODS: Active surveillance of obstetric and paediatric HIV conducted through the National Study of HIV in Pregnancy and Childhood. MAIN OUTCOME MEASURES: Maternal characteristics, pregnancy outcome, use of antiretroviral therapy, mode of delivery and mother-to-child transmission. RESULTS: A total of 8327 pregnancies were reported, increasing from 82 in 1990 to 1394 in 2006, with an increasing proportion from areas outside London. Injecting drug use as the reported risk factor for maternal HIV acquisition declined from 49.2% (185/376) in 1990-1993 to 3.1% (125/4009) in 2004-2006 (P < 0.001), while the proportion of women born in sub-Saharan Africa increased from 43.5% (93/214) in 1990-1993 to 78.6% (3076/3912) in 2004-2006 (P < 0.004). Reported pregnancy terminations decreased from 29.6% (111/376) in 1990-1993 to 3.4% (135/4009) in 2004-2006 (P < 0.001). Most (56.4%, 3717/6593) deliveries were by elective caesarean section, with rates highest in 1999 (66.4%, 144/217). Vaginal deliveries increased from 16.6% (36/217) in 1999 to 28.3% (321/1136) in 2006 (P < 0.001). Use of antiretroviral therapy in pregnancy increased over time, reaching 98.4% (1092/1110) in 2006, and the overall mother-to-child transmission rate declined from 18.5% (35/189) in 1990-1993 to 1.0% (29/2832) in 2004-2006. CONCLUSIONS: The annual number of reported pregnancies increased dramatically between 1990 and 2006, with changing demographic and geographic profiles and substantial changes in pregnancy management and outcome.

Analysis of rubella antibody distribution from newborn dried blood spots using finite mixture models.

Eluted dried blood spot specimens from newborn screening, collected in 2004 in North Thames and anonymously linked to birth registration data, were tested for maternally acquired rubella IgG antibody as a proxy for maternal antibody concentration using an enzyme-linked immunosorbent assay. Finite mixture regression models were fitted to the antibody concentrations from 1964 specimens. The Bayesian Information Criterion (BIC) was used as a model selection criterion to avoid over-fitting the number of mixture model components. This allowed investigation of the independent effect of maternal age and maternal country of birth on rubella antibody concentration without dichotomizing the outcome variable using cut-off values set a priori. Mixture models are a highly useful method of analysis in seroprevalence studies of vaccine-preventable infections in which preset cut-off values may overestimate the size of the seronegative population.

Agreement of rubella IgG antibody measured in serum and dried blood spots using two commercial enzyme-linked immunosorbent assays.

Cases of congenital rubella are now rare in the United Kingdom. However, in certain areas such as London, where a significant proportion of pregnant women has been born abroad and uptake of trivalent measles-mumps-rubella (MMR) vaccination is low, the risk of a rubella outbreak remains. Prior to carrying out a seroprevalence study using rubella IgG antibody in newborn dried blood spots as an indirect marker of maternal immunity, rubella IgG antibody concentrations in serum and dried blood spot samples were investigated. Anonymous paired serum-dried blood spot samples left over from occupational health screening were tested for rubella IgG antibody by two commercially available enzyme-linked immunosorbent assays (ELISAs) (Dade Behring, Marburg, Germany, and Diesse, Siena, Italy). Agreement between serum samples and dried blood spot samples was high for both assays. There were no significant differences in antibody concentrations in paired samples, as 67 of 73 samples tested with the Diesse ELISA (91.8%), and 76 out of 79 samples tested with the Dade Behring ELISA (96.2%) were within two standard deviations of the mean difference. Commercial ELISAs are an appropriate test for seroprevalence surveys based on rubella IgG in dried blood spot samples.

Long-term follow-up of uninfected children born to HIV-infected women and exposed to antiretroviral therapy: survey of parents' and health professionals' views.

Most uninfected children born to diagnosed HIV-infected women are now exposed to antiretroviral therapy (ART) in utero and neonatally and concerns have been raised over the safety of this exposure. To explore parents' and health professionals' views on the long-term follow-up of uninfected children two related surveys were conducted in the UK. Questionnaires were completed by 140 parents/carers and 40 health professionals. Most of the respondents in both surveys (96% overall) acknowledged that it was important to follow up children to identify possible side effects from ART exposure. Almost all respondents (99%) found at least one of the strategies acceptable: follow-up through the clinic, by telephone, post or using data linkage. A third of parents and nearly half of health professionals strongly objected to at least one strategy, mostly postal and clinic contact respectively. The majority of parents (98%) thought they should be told if a potential health risk associated with ART exposure was identified; 73% of parents wanted any direct contact to be through them even when the child had grown up. Almost all respondents were supportive of the rationale for follow-up and, while expressing a preference for certain strategies, generally did not dismiss others. However, developing a single form of long-term follow-up which is both acceptable and feasible is challenging.