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Congenital cytomegalovirus (cCMV) accounts for 20% of all childhood sensorineural hearing loss (SNHL) but is not routinely tested for at birth. Valganciclovir has been shown to prevent hearing deterioration and improve neurocognitive outcomes if started in the first month of life. This study aimed to assess the feasibility of integrating testing for cCMV using salivary swabs into the Newborn Hearing Screening Programme (NHSP). Parents of newborns22 days old in South West London, who were referred after their initial newborn hearing screen for further audiological testing, were approached by hearing screeners to obtain a saliva sample for CMV DNA polymerase chain reaction (PCR). Eighty percent (203/255) of newborns who were eligible had a saliva swab taken by the hearing screener. Over 99% of results were delivered within the first month of life. Two newborns were identified with cCMV and both seen on day 10 of life by the paediatric specialist. All saliva samples tested delivered a result using real-time PCR.It is feasible for hearing screeners to obtain saliva swabs to test for CMV DNA using real-time PCR in newborns referred after their initial hearing screen. Rapid diagnostic testing for cCMV needs a more detailed clinical and cost-effectiveness analysis.

Congenital cytomegalovirus (cCMV) is the most common non-genetic cause of sensorineural hearing loss (SNHL) in children. Ganciclovir has been shown to prevent the continued deterioration in hearing of children with symptomatic cCMV, but some children with cCMV-related SNHL are unidentified in the neonatal treatment period. Neonatal cCMV screening provides an opportunity to identify infants with cCMV-related SNHL who might benefit from early treatment.To assess the feasibility (ability to take samples before 3 weeks of age and clinical assessment by 30 days of age) and acceptability (maternal anxiety) of targeted CMV testing of infants who are 'referred' for further audiological testing after routine newborn hearing screening programme (NHSP).Parents of infants who have 'no clear responses' on routine NHSP before 22 days of life in London and North East England were approached. Salivary and urine samples were tested by CMV PCR. At recruitment and 3 months, the short form Spielberger State-Trait Anxiety Inventory measured maternal anxiety.411 infants were recruited. 99% (407/411) returned a sample; 98% (404/411) successfully yielded a CMV result, 6 had cCMV, all diagnosed on salivary samples taken22 days of age (1.5%; 95% CI 0.6% to 3.2%). Only 50% returned urine samples compared with 99% returning salivary samples (p0.001). Using saliva swabs 98% were successfully screened for CMV within 3 weeks. All positive screening CMV results were known by day 23, and 5/6 infants with cCMV were assessed within 31 days. Anxiety was not increased in mothers of infants screened for cCMV.Targeted salivary screening for cCMV within the NHSP is feasible, acceptable and detects infants with cCMV-related SNHL who could benefit from early treatment.

UNLABELLED Screening for a condition should only be undertaken if certain strict criteria are met. Congenital CMV (cCMV) is a leading cause of sensorineuronal hearing loss (SNHL) and meets many of these criteria, but is not currently screened for in the UK. Ganciclovir reduces CMV-induced progressive SNHL if treatment is begun in the first month of life. The Newborn Hearing Screening Programme (NHSP) has been shown to identify SNHL at the earliest possible age. The potential of integrating screening for cCMV into the NHSP is discussed to consolidate the link between screening, early diagnosis and management. CONCLUSION The early diagnosis and treatment of cCMV may prevent a small proportion of late SNHL. In the absence of any screening programme, we provide evidence that clinically targeted screening through the NHSP is a potential option in the UK, enhancing the diagnostic pathway and enabling appropriate early treatment to reduce long-term morbidity.

BACKGROUND: Protein-polysaccharide vaccines have made a significant impact on the burden of disease caused by encapsulated bacteria such as Streptococcus pneumoniae, Haemophilus influenzae, Neisseria meningitidis, and have the potential to do so for Salmonella Typhi. Nepal is one of many resource-poor nations with limited information on the epidemiology of childhood infections caused by these pathogens. METHODS: Over a 21-month period, we studied children aged ≤12 years admitted to an urban hospital in Nepal with suspected bacteremia, meningitis, or pneumonia. Patan Hospital is a non-profit hospital with the second largest pediatric unit in the Kathmandu Valley. RESULTS: Of 2039 children enrolled in the study, 142 (7.5%) included in the analysis had positive blood cultures. The agents of enteric fever, Salmonella Typhi and Salmonella Paratyphi, accounted for 59/142 (42%) of all bacteremias and were the most frequently cultured pathogens in children ≥1 year of age. S. pneumoniae was isolated in 16% of positive blood cultures and was the most common cause of bacteremia in children

Background Congenital cytomegalovirus (cCMV) is an important cause of childhood deafness, which is modifiable if diagnosed within the first month of life. Targeted screening of infants who do not pass their newborn hearing screening tests in England is a feasible approach to identify and treat cases to improve hearing outcome. Aims To conduct a cost analysis of targeted screening and subsequent treatment for cCMV-related sensorineural hearing loss (SNHL) in an, otherwise, asymptomatic infant, from the perspective of the UK National Health Service (NHS). Methods Using data from the newborn hearing screening programme (NHSP) in England and a recent study of targeted screening for cCMV using salivary swabs within the NHSP, we estimate the cost (in UK pounds (£)) to the NHS. The cost of screening (time, swabs and PCR), assessing, treating and following up cases is calculated. The cost per case of preventing hearing deterioration secondary to cCMV with targeted screening is calculated. Results The cost of identifying, assessing and treating a case of cCMV-related SNHL through targeted cCMV screening is estimated to be £6683. The cost of improving hearing outcome for an infant with cCMV-related SNHL through targeted screening and treatment is estimated at £14 202. Conclusions The costs of targeted screening for cCMV using salivary swabs integrated within NHSP resulted in an estimate of cost per case that compares favourably with other screening programmes. This could be used in future studies to estimate the full economic value in terms of incremental costs and incremental health benefits.

Aim: Infection is an important cause of neonatal and infant mortality. We evaluatedchanges in infant deaths from infections from 1988 to 2008 in the North of England. Methods: We interrogated a population-based survey and reviewed infant deaths frominfection. Proportional contribution to deaths, pathogens identified and risk factors wereanalysed. Results: Thirteen percentage of 4366 infant deaths from a population of 704 536livebirths were infectious. The absolute numbers of infant deaths from infection fell overtime but the proportion of deaths from infection increased (12.1%, 13.6% and 14.9%).Significantly preterm infants were increasingly represented in successive epochs (14%,24% and 38%). Infant mortality rate (IMR) from meningococcus and Group BStreptococcus (GBS) fell in the latest epoch, but there was a corresponding increase fromEscherichia coli and candida. Discussion: This large study shows that infections have become proportionately moreimportant causes of death especially in very preterm infants. Recent significant reductionsin death from meningococcus and GBS are likely to represent successful achievements ofvaccination and antibiotic prophylactic policies. Increases in IMR from E. coli may relate toGBS prophylaxis and increases in candida to the increase from preterm populations.Further efforts to understand these changing patterns and develop additional preventionand treatment strategies and vaccines remain an urgent priority.INTRODUCTIONDespite medical advances data suggest that infectionscontinue to have a significant impact on neonatal andinfant mortality even in developed countries (1,2). Deathcertificate studies in the United Kingdom (UK) (3,4)highlight the total burden and the large number of causesof infections on neonatal and infant mortality. However,detailed clinical data that might help focus efforts atreduction in cases are currently lacking.Data currently suggests that all-cause neonatal and infantmortality rates have steadily decreased in the UK in the last25 years. A proportion of these reductions are accountedfor by changes in vaccine preventable diseases particularlymeningococcus, Haemophilus influenzae type b and pneu-mococcus (5), but there is little data available describinghow all-cause infectious neonatal and infant mortality rateshave changed in this time period. There are many factorsthat affect the observed epidemiological patterns includingchanges to immunization schedules, improvements indiagnostic techniques and medical management, and anincreasing preterm population, in part as a consequence ofincreasing survival of the most immature.There are few long-term population-based data describ-ing the epidemiology of infectious death in infancy. Weaimed to describe the contribution of infections to infantmortality in a well-defined population in the UK andexplore how this has changed over a 21-year period.METHODSWe used the Perinatal Mortality Survey (PMS) database,coordinated by the Regional Maternity Survey Office(RMSO) in the North of England. This well-validatedpopulation-based survey captures the death of all live-borninfants of mothers resident in the North East and NorthCumbria within the first post-natal year, including infantswho were born or died outside the region. Deaths are

Objective To determine the role of viral infections in causing fetal and infant death. Study design We assessed a well-validated population database of fetal (≥20 weeks gestation) and infant death for infective deaths and deaths from viruses over a 21-year period (1988-2008). We analyzed by specific viral cause, timing (late fetal loss [20-23 weeks], stillbirth [≥24 weeks], neonatal death [0-27 days], and post-neonatal infant death [28-364 days]) and across time. Results Of the 989 total infective deaths, 108 were attributable to viral causes (6.5% of late fetal losses, 14.5% of stillbirths, 6.5% of neonatal deaths, and 19.4% of postneonatal infant deaths). Global loss (combined fetal and infant losses per 100 000 registerable births) was 139.6 (95% CI, 130.9-148.3) for any infective cause and 15.2 (95% CI, 12.3-18.1) for viral infections. More than one-third (37%) of viral-attributed deaths were before live birth, from parvovirus (63%) or cytomegalovirus (33%). Parvovirus accounted for 26% (28 of 108) of all viral deaths. Cytomegalovirus was associated with a global loss rate of 3.1 (95% CI, 1.8-4.4) and an infant mortality rate of 1.3 (95% CI, 0.4-2.1) per 100 000 live births; 91% of cases were congenital infections. Herpes simplex virus caused death only after live births (infant mortality rate, 1.4; 95% CI, 0.5-2.3). No changes in rates were seen over time. Conclusion We have identified a substantial contribution of viral infections to global fetal and infant losses. More than one-third of these losses occurred before live births. Considering our methodology, our estimates represent the minimum contribution of viral illness. Strategies to reduce this burden are needed.

Clostridium septicum infection in humans is rare and this is the second case report of focal C septicum brain abscesses associated with Escherichia coli 0157 haemolytic uraemic syndrome (HUS). The case presented in a child who lived on a rural farm. The abscesses initially progressed despite 7emsp14;months of appropriate antibiotic therapy and repeated image-guided aspiration. After definitive resection and prolonged antibiotic therapy, there was no recurrence. This case reminds us of this rare but important neurological complication of HUS and supports consideration of early definitive neurosurgical intervention in similar unusual cases.

CMV is the most common congenital infection in newborns worldwide. Congenital CMV causes sensorineural hearing loss in a significant proportion of infected newborns, while the majority of newborns are asymptomatic. In the last three years there have been significant advances in the diagnosis and treatment of congenital CMV. We have developed practical evidence based guidelines for the management of congenital CMV.

Background Infection is a major cause of perinatal, neonatal and infant deaths, but the viral contribution to these deaths is poorly described. Objective To describe the contribution of viruses to perinatal, neonatal and infant deaths in one Region of the UK (1985–2008). Methods Using Regional Perinatal Mortality Survey – a population based database of fetal deaths ≥20 weeks gestation and in live-born individuals within the first year. Deaths from viral infection were identified, verified and specified. Results From 819 890 live births and 4478 stillbirths (>24 weeks) 1123 deaths were infectious: 585 bacterial, 102 viral. Of viral deaths 29% were parvovirus (mostly stillbirths); 23% were cytomegalovirus (CMV) (mostly stillbirths). 92% of CMV cases were congenital (cCMV). 23 infant deaths were due to respiratory viruses (table 1). Conclusions Viruses caused 9% of all infective deaths: 6% of fetal losses 24 weeks, 5% of neonatal deaths and 15% of non-neonatal infant deaths. In this population viral deaths occur in ∼7:100 000 live-births and 6:1000 stillbirths ≥24 weeks, most commonly from parvovirus or CMV. By comparison 13% of these deaths were attributed to GBS infection. Morbidity from cCMV is more common than mortality: this population has considerable burden from cCMV.

Background Congenital CMV (cCMV) causes up to 15% sensorineural hearing loss (SNHL) in the UK, however hearing outcomes may improve with ganciclovir treatment commencing in the first month of life. Targeted screening of infants who are ‘referred’ for further audiological testing after ‘no clear responses’ are found on their newborn hearing screen for CMV might identify these babies early enough to offer treatment. Aims We present initial feasibility and acceptability data of targeted cCMV screening. Methods Eligible infants from Northumbria and South-West London, (those9 referred9 for further hearing testing after their newborn hearing screening and Results Of 14,373 newborns 351 were9 referred9 for further hearing testing after their initial hearing screening and 248 families were approached with 152 (62%) agreeing to cCMV screening. Three newborns were found positive, all detected in time to allow assessment for treatment within 28 days. Salivary samples were easier to acquire with 95% (145) returning salivary samples and 41% (63) urine samples. Anxiety scores in study mothers were not significantly different to reference mothers. Conclusions Targeted cCMV screening using saliva is feasible and acceptable to parents. Extending the National screening programme to include cCMV testing in all infants without clear early hearing responses may improve hearing outcomes. Economic analysis and mechanistic processes require further evaluation.

BACKGROUND: Streptococcus pneumoniae is a leading cause of pneumonia and meningitis in young children. Before implementation of the pneumococcal conjugate vaccine in developing countries, there is an urgent need to provide regional epidemiological data on pneumococcal disease. The aims of this study were to determine the prevalence and serotype distribution of invasive pneumococcal disease among young children hospitalized in urban Nepal. METHODS: Children aged 2 months to 5 years who were admitted to Patan Hospital, Kathmandu, with fever and/or suspected pneumonia, meningitis, or bacteremia were recruited. Blood culture specimens were collected from all participants. In cases of suspected meningitis, cerebrospinal fluid specimens were cultured and were tested for S. pneumoniae antigen. RESULTS: A total of 885 children were recruited during the 21-month study period. Of these, 76 (9%) had meningitis and 498 (56%) had pneumonia, on the basis of clinical criteria. Radiographically confirmed pneumonia occurred in 354 (40%), and probable or definite meningitis occurred in 47 (5%). S. pneumoniae was isolated in specimens from 17 (2%) of the children. Serotypes 1 and 12A were isolated most frequently, and only 1 of 17 isolates had a serotype contained in the currently available 7-valent pneumococcal conjugate vaccine. CONCLUSIONS: More than 60% of children aged