Guidelines and practice of breastfeeding in women living with HIV-Results from the European INSURE survey.

INTRODUCTION: Antiretroviral therapy (ART) is integral to HIV prevention, including averting vertical transmission. The World Health Organization (WHO) recommends ART and breastfeeding for all women living with HIV for at least 12 months post-partum [1, 2]. Much of the data on HIV transmission through breastfeeding comes from low-resource settings, with a paucity of data on breastfeeding-related HIV transmission in women living with HIV in other settings. Women Against Viruses in Europe (WAVE), part of the European AIDS Clinical Society (EACS), aims to improve the standard of care for women living with HIV and sought to gain an understanding of breastfeeding guidelines and practice in women living with HIV across Europe. METHODS: A steering group convened by WAVE developed a survey to collate information on breastfeeding trends, practice, and guideline recommendations for women living with HIV in Europe and to establish interest in becoming involved in a collaborative breastfeeding network. The survey was disseminated to 31 countries in March 2022. RESULTS: In total, 25 eligible responses were received: 23/25 (92%) countries have HIV and pregnancy guidelines; 23/23 (100%) guidelines refer specifically to breastfeeding; 12/23 (52%) recommend against breastfeeding; 11/23 (48%) offer an option if certain criteria are met; 12/25 (48%) reported that the number of women living with HIV who breastfeed is increasing; 24/25 (96%) respondents were interested in joining a network on breastfeeding in women living with HIV. CONCLUSIONS: Recommendations vary, and nearly half of the guidelines recommend against breastfeeding. Many countries report an increase in breastfeeding. WAVE will establish a collaborative network to bridge data gaps, conduct research, and improve support for women living with HIV who choose to breastfeed.

Evolution of the intracranial features of congenital cytomegalovirus on MRI.

AIM: To describe the evolution of the intracranial features of congenital cytomegalovirus (cCMV) on magnetic resonance imaging (MRI). MATERIALS AND METHODS: Sixteen infants with polymerase chain reaction (PCR)-confirmed cCMV who had undergone at least two MRI examinations of the brain were identified. Two paediatric neuroradiologists reviewed the baseline studies retrospectively for intracranial features of cCMV, including white matter signal abnormalities, subependymal cysts, malformations of cortical development, and intracranial calcification. The subsequent MRI studies were then reviewed and directly compared to the baseline examinations. RESULTS: White matter signal abnormalities were seen on all 16 baseline studies (100%); these persisted on all subsequent examinations but were patchier, more focal, and associated with an interval reduction in white matter volume. Subependymal cysts were present on 11 (69%) of the baseline scans; these almost universally regressed (in 10 of the 11 cases [91%]), with no new cysts appreciable on subsequent imaging. Malformations of cortical development, exclusively in the form of polymicrogyria, were seen in six (38%) patients and persisted, unchanged, on subsequent imaging. Intracranial calcification was seen in a minority of baseline studies (4 [25%]) and remained stable on subsequent scans. CONCLUSION: Children with cCMV who present later in life without an established or suspected underlying pathology can pose a challenge to the assessing radiologist. The radiological sequelae of cCMV can be non-specific; in some cases, white matter signal abnormalities and focal loss of white matter volume may be the only intracranial features. It is therefore important that radiologists are aware of cCMV as a potential differential for these findings.

Healthcare-worker-associated outbreak of Panton-Valentine-leukocidin-producing meticillin-sensitive Staphylococcus aureus in a large neonatal unit in London: successful targeted suppression therapy following failure of mass suppression therapy.

BACKGROUND: Staphylococcus aureus is a leading cause of healthcare-associated infection, and outbreaks have been associated with neonatal units and colonization of healthcare workers. AIM: To describe an outbreak of Panton-Valentine-leukocidin-producing meticillin-sensitive Staphylococcus aureus (PVL-MSSA) in a neonatal intensive care unit. METHODS: Multi-disciplinary outbreak control investigation. RESULTS: Over a period of 16 months, seven neonates were identified as positive for PVL-MSSA. Isolates were identified in blood cultures (two patients), nasopharyngeal aspirate (one patient) and rectal screening swabs (four patients). Epidemiological and whole-genome sequencing data suggested a long-term carrier as the most likely source. Despite two rounds of mass suppression therapy of staff, using chlorhexidine initially followed by octenidine-based regimens, positive patients continued to be identified. Staff screening subsequently identified one healthcare worker colonized with the outbreak strain of PVL-MSSA who underwent enhanced screening and further suppression therapy. No further cases have been identified to date. Compliance with mass suppression therapy was >95% and a post-administration staff satisfaction survey showed that the majority of staff agreed with the steps taken, with low rates of adverse reactions. CONCLUSION: S. aureus outbreaks are commonly associated with colonization of healthcare workers, and are challenging to manage within environments such as neonatal units. This study highlights the utility of whole-genome sequencing in identifying and mapping an outbreak. It is recommended that targeted staff screening should be considered early in similar outbreaks. In this setting, mass suppression therapy was not an effective strategy despite a high level of staff engagement and compliance.

Diagnostic analysis of baseline brain MRI features in infants with congenital cytomegalovirus infection: a simplified scoring system.

AIM: To characterise the magnetic resonance imaging (MRI) features of infants with congenital cytomegalovirus (CMV) and categorise those into a simplified MRI scoring system. MATERIALS AND METHODS: Three neuroradiologists reviewed the examinations of 71 infants retrospectively and scored for the presence of a white matter signal abnormality and structural lesion and each MRI was given a score of 0, 1, 2, or 3 for normal, structural abnormality alone, white matter abnormality alone, white matter abnormality plus structural lesion, respectively. Imaging features were outlines according to symptomatology. Chi-square and Spearman's rho were used to test relationships between MRI features and viral loads and MRI score/symptomatic disease respectively. Cohen's Kappa coefficient was used to assess interobserver agreement. RESULTS: Of the 49 abnormal studies, 40% (n=20) were seen in asymptomatic infants. The commonest finding was white matter signal abnormality, followed by cyst formation and polymicrogyria (86%, n=42; 71%, n=35; and 33%, n=16, respectively). Cysts were significantly positively correlated with white matter abnormalities and polymicrogyria. On the MRI score, 31%, 10%, 15%, and 44% obtained a score of 0, 1, 2, and 3, respectively; the MRI score was positively correlated with log-transformed viral loads. Interobserver agreement for the presence of white matter signal abnormality, cyst formation, malformations of cortical development (MCD), and global MRI score was excellent (k = 0.82, 0.94, 0.96, and 0.86, respectively). CONCLUSION: Baseline MRI provides information valuable for treatment decisions, especially in "asymptomatic" infants. The simplified scoring system is easier to use, incorporating solely the imaging findings that are anticipated to have an effect on clinical outcome.

Mortality and AIDS-defining events among young people following transition from paediatric to adult HIV care in the UK.

OBJECTIVES: To investigate risk of AIDS and mortality after transition from paediatric to adult care in a UK cohort of young people with perinatally acquired HIV. METHODS: Records of people aged ≥ 13 years on 31 December 2015 in the UK paediatric HIV cohort (Collaborative HIV Paediatric Study) were linked to those of adults in the UK Collaborative HIV Cohort (CHIC) cohort. We calculated time from transition to a new AIDS event/death, with follow-up censored at the last visit or 31 December 2015, whichever was the earliest. Cumulative incidence of and risk factors for AIDS/mortality were assessed using Kaplan-Meier and Cox regression. RESULTS: At the final paediatric visit, the 474 participants [51% female, 80% black, 60% born outside the UK, median (interquartile range) age at antiretroviral therapy (ART) initiation = 9 (5-13) years] had a median age of 18 (17-19) years and CD4 count of 471 (280-663) cell/µL; 89% were prescribed ART and 60% overall had a viral load ≤ 400 copies/mL. Over median follow-up in adult care of 3 (2-6) years, 35 (8%) experienced a new AIDS event (n = 25) or death (n = 14) (incidence = 1.8/100 person-years). In multivariable analyses, lower CD4 count at the last paediatric visit [adjusted hazard ratio = 0.8 (95% confidence interval: 0.7-1.0)/100 cells/µL increment] and AIDS diagnosis in paediatric care [2.7 (1.4-5.5)] were associated with a new AIDS event/mortality in adult care. CONCLUSIONS: Young people with perinatally acquired HIV transitioning to adult care with markers of disease progression in paediatric care experienced poorer outcomes in adult care. Increased investment in multidisciplinary specialized services is required to support this population at high risk of morbidity and mortality.

COVID-19-Associated Cytotoxic Lesions of the Corpus Callosum.

There are very limited published data on the neurologic complications associated with coronavirus disease 2019 (COVID-19) in the pediatric population. Here we present the first 2 pediatric cases of presumed COVID-19 related cytotoxic lesions of the corpus callosum. Similar to reports in adults, these cases suggest that the COVID-19 infection in children may rarely mediate a hyperinflammatory response that can cause CNS pathology. As the pandemic continues further, the presentation of cytotoxic lesions of the corpus callosum should prompt radiologists to consider COVID-19, among other known causes.

The optimal time to test for sero-reversion in HIV-exposed uninfected infants: the later the better?

OBJECTIVES: HIV-exposed uninfected (HEU) infants are tested for loss of maternal antibody (sero-reversion) at 18 months of age. Highly sensitive fourth-generation antigen/antibody assays can detect very low levels of antibody, leading to retesting. We audited serological screening outcomes in HEU infants at two National Health Service (NHS) Trusts. METHODS: HEU infants born between January 2013 and August 2016 were identified via case records. Data collected included gestation; age at testing; test results and assay type. RESULTS: One hundred and forty-two infants were identified, of whom 21 were excluded from analysis. One hundred and one (83%) were born at term and 20 (17%) preterm (< 37/40 weeks of gestation), and the median age at first serology was 19.1 [interquartile range (IQR) 18.1; 21.4] months. Initial serology was positive in 10 of 121 infants (8.3%), and the median age of these 10 infants was 18.3 (IQR 18.1; 18.8) months, whereas those with negative serology (n = 111) had a median age of 19.2 (IQR 18.1; 21.5) months (P = 0.12). All infants with positive HIV serology were born at term. Seven of 10 infants had reactive serology on two fourth-generation assays. Subsequent serology was available for eight of 10 infants, with a median age of 21.3 months. Five of the eight (63%) were negative. One was reactive but HIV RNA polymerase chain reaction (PCR) was negative, and one was reactive on screening but negative on confirmatory testing. The remaining child was still seropositive at 24.7 months but had a non-reactive result at 29.4 months. CONCLUSIONS: Overall, 8.3% of HEU infants required repeat testing to confirm loss of antibody. Delaying testing until 22 months of age reduces retesting to < 2%, with associated resource and emotional implications. Positive serology at 22 months should prompt an HIV RNA PCR to exclude infection.

Is it not time for international guidelines to combat congenital cytomegalovirus infection? A review of central nervous system manifestations.

Cytomegalovirus (CMV) is the most commonly transmitted virus in utero with a prevalence of up to 1.5%. The infection has potentially debilitating and devastating consequences for the infected fetus, being a leading cause for neurological disability worldwide. Once acquired, it often goes undetected with only an assumed 10% of infected neonates displaying the classic clinical or imaging features. Viral DNA polymerase chain reaction (PCR) of saliva or urine obtained within the first 21 days of life is required to make the diagnosis. As the majority of infected neonates are initially asymptomatic, diagnosis is often delayed. An abnormal routine neonatal hearing test and characteristic antenatal cranial ultrasound imaging findings may raise the suspicion of congenital CMV (cCMV) in the asymptomatic group. Ultimately, the aim is to facilitate early diagnosis and timely treatment. In this article, we highlight diagnostic and treatment challenges of the commonest congenital infection, we present the current available central nervous system imaging severity grading systems, and highlight the need for an internationally agreed diagnostic grading system that can aid treatment decision-making.

Persistence of HIV reservoir following successful haematopoietic stem cell transplant for juvenile myelomonocytic leukaemia in a child with perinatally acquired HIV.

This report describes a case of juvenile myelomonocytic leukaemia (JMML) on a background of both perinatally acquired HIV infection and congenital cytomegalovirus, and management of antiretroviral therapy during haematopoietic stem cell transplant. Peripheral blood HIV viral load remained below the lower limit of detection throughout and following transplant and is currently <20 RNA copies/mL. The child is currently in remission from JMML, but HIV DNA remains detectable despite myeloablative conditioning and sustained plasma HIV viral suppression.

Paediatric European Network for Treatment of AIDS (PENTA) guidelines for treatment of paediatric HIV-1 infection 2015: optimizing health in preparation for adult life.

The 2015 Paediatric European Network for Treatment of AIDS (PENTA) guidelines provide practical recommendations on the management of HIV-1 infection in children in Europe and are an update to those published in 2009. Aims of treatment have progressed significantly over the last decade, moving far beyond limitation of short-term morbidity and mortality to optimizing health status for adult life and minimizing the impact of chronic HIV infection on immune system development and health in general. Additionally, there is a greater need for increased awareness and minimization of long-term drug toxicity. The main updates to the previous guidelines include: an increase in the number of indications for antiretroviral therapy (ART) at all ages (higher CD4 thresholds for consideration of ART initiation and additional clinical indications), revised guidance on first- and second-line ART recommendations, including more recently available drug classes, expanded guidance on management of coinfections (including tuberculosis, hepatitis B and hepatitis C) and additional emphasis on the needs of adolescents as they approach transition to adult services. There is a new section on the current ART 'pipeline' of drug development, a comprehensive summary table of currently recommended ART with dosing recommendations. Differences between PENTA and current US and World Health Organization guidelines are highlighted and explained.

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.

The influence of paediatric HIV infection on circulating B cell subsets and CXCR5(+) T helper cells.

Antiretroviral therapy (ART) only partially restores HIV-induced alterations in lymphocyte populations. We assessed B and T cell phenotypes in a cohort of children from a single centre in the United Kingdom with perinatally acquired HIV compared to healthy controls. The majority of HIV infected children (44 of 56) were on fully suppressive combination ART. Children with perinatally acquired HIV had significantly lower memory B and CD4(+) CD45RO(+) CXCR5(+) [follicular T helper cell (Tfh)-like] T cell percentages. Detectable viraemia was associated with higher CD21(-) (activated and exhausted/tissue-like memory) B cells. A greater proportion of life spent on suppressive ART was associated with higher memory B cell percentages. These results suggest that early and sustained suppressive ART may preserve B and T cell phenotypes in perinatally acquired HIV and limit deficits in humoral immunity. A lower proportion of circulating Tfh-like cells in HIV infected children appears to be independent of HIV treatment history and ongoing HIV viraemia and warrants further investigation.

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.

Outcome of IVF/ICSI referrals from the Royal Alexandra Hospital (level 2 infertility service) to Glasgow Royal Infirmary (level 3 infertility service).

In a 2-year period (2004 and 2005), 117 couples with infertility were referred from secondary care for IVF/ICSI treatment. This study describes the age, waiting times, diagnostic categories and outcomes for all couples referred. A total of 59% (69) of all couples referred conceived. Of these, 25% (29 couples) conceived spontaneously or as a result of simpler treatments and 34% (40 couples) conceived following IVF/ICSI treatment. The twin pregnancy rate following IVF/ICSI was 25% and the average waiting time from referral to treatment was 13-18 months. Couples with female factor infertility (excluding endometriosis) and couples with unexplained infertility experienced a higher spontaneous pregnancy rate while awaiting IVF/ICSI treatment, than those couples with male factor or combined infertility. However, couples with male factor or combined infertility achieved much higher success rates with IVF/ICSI treatment.

Pregnancy in type 2B VWD: a case series.

Type 2B von Willebrand disease (VWD) is a rare, inherited bleeding disorder resulting from a qualitative defect in von Willebrand factor (VWF). There is very little published information on how to quantify bleeding risk and manage haemostasis in type 2B VWD patients during pregnancy. This article presents the changes in VWF parameters and details of patient management and delivery outcomes for four pregnancies in three women with two different mutations causing type 2B VWD. We report an unexpected rise in the VWF:Ag at 37 weeks gestation in two sisters with R1306W associated with significant thrombocytopenia. These patients were supported with platelet transfusions as well as intermediate purity VWF-FVIII plasma concentrates during the peri- and postpartum periods. No thrombocytopenia was observed in our third case with a mutation encoding an R1308C substitution; haemostatic support was with intermediate purity VWF-FVIII plasma concentrates alone. No adverse bleeding events occurred and in all cases a live healthy infant was delivered. One patient was readmitted post partum with bleeding symptoms due to retained placenta; no further haemostatic support was given at this time. This case series is the first to detail the progression of laboratory parameters, management and outcomes of pregnancy in patients with type 2B VWD. The cases illustrate some of the challenges posed by the increased production of a VWF variant with a gain-of-function effect. The rapid coagulation changes observed in this series illustrate the need for continual monitoring of VWF parameters and platelet count throughout pregnancy in women with type 2B VWD.

Minimising twins in in vitro fertilisation: a modelling study assessing the costs, consequences and cost-utility of elective single versus double embryo transfer over a 20-year time horizon.

OBJECTIVES: To assess the cumulative costs and consequences of double embryo transfer (DET) or elective single embryo transfer (eSET) in women commencing in vitro fertilisation (IVF) treatment aged 32, 36 and 39 years. DESIGN: Microsimulation model. SETTING: Three assisted reproduction centres in Scotland. SAMPLE: A total of 6153 women undergoing treatment at one of three Scottish IVF clinics, between January 1997 and June 2007. METHODS: A microsimulation model, populated using data inputs derived from a large clinical data set and published literature, was developed to compare the costs and consequences of using eSET or DET over multiple treatment cycles. MAIN OUTCOME MEASURES: Disability-free live births; twin pregnancy rate; women's quality-adjusted life-years (QALYs); health service costs. RESULTS: Not only did DET produce a higher cumulative live birth rate compared with eSET for women of all three ages, but also a higher twin pregnancy rate. Compared with eSET, DET ranged from costing an additional £ 27,356 per extra live birth in women commencing treatment aged 32 years, to costing £ 15,539 per extra live birth in 39-year-old women. DET cost ∼ £ 28,300 and ∼ £ 20,300 per additional QALY in women commencing treatment aged 32 and 39 years, respectively. CONCLUSIONS: Considering the high twin pregnancy rate associated with DET, coupled with uncertainty surrounding QALY gains, eSET is likely to be the preferred option for most women aged ≤ 36 years. The cost-effectiveness of DET improves with age, and may be considered cost-effective in some groups of older women. The decision may best be considered on a case-by-case basis for women aged 37-39 years.

Clomifene citrate and intrauterine insemination as first-line treatments for unexplained infertility: are they cost-effective?

BACKGROUND: First-line treatments for unexplained infertility traditionally include clomifene citrate (CC) or unstimulated intrauterine insemination (IUI). A recently published randomized controlled trial considered the effectiveness of CC and IUI in patients with unexplained infertility and found that neither treatment offered a superior live birth rate when compared with expectant management (EM). This paper reports the economic evaluation conducted alongside this trial in order to assess whether health care providers are gaining value for money in this clinical area. METHODS: Five hundred and eighty women across five Scottish hospitals were randomized to either EM, CC or IUI for 6 months. The primary outcome measure was live births. Resource-use data were collected during the trial and costs were calculated from a UK National Health Service (NHS) perspective. Incremental cost-effectiveness ratios were calculated, expressed as cost per live birth, in order to compare the cost-effectiveness of CC and IUI with that of EM to treat unexplained infertility. RESULTS: Live birth rates in the three randomized groups were: EM = 32/193 (17%), CC = 26/194 (13%) and IUI = 43/193 (22%). The mean (standard deviation) costs per treatment cycle were £0 for EM, £83 (£17) for CC and £98 (£31) for IUI. The mean treatment costs per patient for EM, CC and IUI were £12 (£117), £350 (£220) and £331 (£222), respectively. The cost per live birth for EM, CC and IUI was £72 (95% confidence interval £0-£206), £2611 (£1870-£4166) and £1487 (£1116-£2155), respectively. The incremental cost-effectiveness ratio for IUI versus EM was £5604 (-£12204 to £2227), with CC dominated by IUI. CONCLUSIONS: Despite being more expensive, existing treatments such as empirical CC and unstimulated IUI do not offer superior live birth rates compared with EM of unexplained infertility. They are unlikely to be a cost-effective use of limited NHS resources. The study's main limitation is that it did not consider the psychological effects on couples. ISRCT Number: 71762042.

Bilateral idiopathic avascular necrosis of the scaphoid: a rare case of Preiser's disease.

Whereas avascular necrosis of the scaphoid after a fracture is well-documented, idiopathic avascular necrosis of the scaphoid (Preiser's disease) is rare. Little is known of the aetiology of the condition and even less about the best course of management. We describe a rare case of bilateral Preiser's disease. Possible aetiological factors and a summary of the current concepts of management are discussed.

Severe invasive Panton-Valentine Leucocidin positive Staphylococcus aureus infections in children in London, UK.

OBJECTIVE: To describe the features of invasive Panton-Valentine Leucocidin positive Staphylococcus aureus (PVL-SA) in children at a London teaching hospital, from 2004 to 2008. METHODS: Retrospective case note review. RESULTS: Eleven previously healthy children, 7 male, median age 9 years (range 7 months-13 years), had invasive infections due to unrelated community-acquired meticillin-sensitive PVL-SA. Possible risk factors were identified in 10 cases. Eight patients had complicated musculoskeletal infections, 2 had pneumonia, and 1 had a massive retropharyngeal abscess. At admission neutropenia was present in 2 patients, deep vein thrombosis in 3, and initial blood cultures were positive in 8. Patients with musculoskeletal involvement had a median of 3 (range 1-6) sites of infection, and required median 5 (range 1-11) operative procedures. Eight patients were admitted to PICU, 7 had septic shock. Median duration of hospital stay was 51 (range 14-255) days. One child died and 5 have long-term morbidity. CONCLUSIONS: The clinical features of invasive PVL-SA in this series were similar to those reported from USA and Europe. Musculoskeletal infection was the most common manifestation, frequently progressing to multiple sites and severe sepsis. Most cases had risk factors and clinical features which might have allowed earlier diagnosis, and possibly improved outcome.