Infant Prophylaxis Research Articles

Animal models of respiratory syncytial virus infection

Human respiratory syncytial virus (hRSV) is a major cause of respiratory disease and hospitalisation of infants, worldwide, and is also responsible for significant morbidity in adults and excess deaths in the elderly. There is no licensed hRSV vaccine or effective therapeutic agent. However, there are a growing number of hRSV vaccine candidates that have been developed targeting different populations at risk of hRSV infection. Animal models of hRSV play an important role in the preclinical testing of hRSV vaccine candidates and although many have shown efficacy in preclinical studies, few have progressed to clinical trials or they have had only limited success. This is, at least in part, due to the lack of animal models that fully recapitulate the pathogenesis of hRSV infection in humans. This review summarises the strengths and limitations of animal models of hRSV, which include those in which hRSV is used to infect non-human mammalian hosts, and those in which non-human pneumoviruses, such as bovine (b)RSV and pneumonia virus of mice (PVM) are studied in their natural host.Apart from chimpanzees, other non-human primates (NHP) are only semi-permissive for hRSV replication and experimental infection with large doses of virus result in little or no clinical signs of disease, and generally only mild pulmonary pathology. Other animal models such as cotton rats, mice, ferrets, guinea pigs, hamsters, chinchillas, and neonatal lambs are also only semi-permissive for hRSV. Nevertheless, mice and cotton rats have been of value in the development of monoclonal antibody prophylaxis for infants at high risk of severe hRSV infection and have provided insights into mechanisms of immunity to and pathogenesis of hRSV. However, the extent to which they predict hRSV vaccine efficacy and safety is unclear and several hRSV vaccine candidates that are completely protective in rodent models are poorly effective in chimpanzees and other NHP, such as African Green monkeys. Furthermore, interpretation of findings from many rodent and NHP models of vaccine-enhanced hRSV disease has been confounded by sensitisation to non-viral antigens present in the vaccine and challenge virus.Studies of non-human pneumoviruses in their native hosts are more likely to reflect the pathogenesis of natural hRSV infection, and experimental infection of calves with bRSV and of mice with PVM result in clinical disease and extensive pulmonary pathology. These animal models have not only been of value in studies on mechanisms of immunity to and the pathogenesis of pneumovirus infections but have also been used to evaluate hRSV vaccine concepts. Furthermore, the similarities between the epidemiology of bRSV in calves and hRSV in infants and the high level of genetic and antigenic similarity between bRSV and hRSV, make the calf model of bRSV infection a relevant model for preclinical evaluation of hRSV vaccine candidates which contain proteins that are conserved between hRSV and bRSV.

Cost-effectiveness of palivizumab compared to no prophylaxis in term infants residing in the Canadian Arctic.

Hospital admissions for respiratory syncytial virus infection result in large health expenditures for Inuit infants. Palivizumab has been shown to be highly effective in reducing such admissions in preterm Inuit infants. We performed a cost-effectiveness analysis estimating the incremental cost-effectiveness ratio (ICER) for palivizumab prophylaxis per admission related to respiratory syncytial virus avoided in healthy term infants across the Canadian Arctic. We compared universal palivizumab prophylaxis in term infants less than 6 months of age to no prophylaxis in 8 Arctic regions: the Northwest Territories, Nunavut, Nunavut without Iqaluit, the 3 subregions of Nunavut (Kitikmeot, Kivalliq and Qikiqtaaluk), the Qikiqtaaluk Region without Iqaluit, and Nunavik (northern Quebec). Costs were acquired from the territorial governments, hospitals and contracted agencies. The perspective is that of the public payer, with a 6-month timeline. In scenario A, universal prophylaxis was provided until the end of the respiratory syncytial virus season, and in scenario B, infants received prophylaxis until 5 months of age. The ICERs of scenario A were compared with those of scenario B. Under scenario A, the cost per admission avoided was as high as $546 115 in the Northwest Territories, compared with a cost savings of $36 145 in the Kitikmeot Region. Under scenario B, the ICER showed cost savings of $48 549 in the Kitikmeot Region and $2731 in the Kivalliq Region, with low ICERs in Nunavik of $15 601. Considerable cost savings were found for the Kitikmeot Region with universal palivizumab prophylaxis in term infants with both scenarios, whereas cost savings were found for the Kivalliq Region with scenario B. Stopping prophylaxis at 5 months of age was a more cost-effective strategy in all regions except the Kitikmeot Region. Nunavik had low ICERs, and prophylaxis should be considered for this region.

The Swedish infant high-grade reflux trial: Study presentation and vesicoureteral reflux outcome

High-grade vesicoureteral reflux (VUR) in infants is associated with congenital renal abnormalities, recurrent UTI, and bladder dysfunction. Endoscopic treatment (ET) is a well-established method in children with low to moderate reflux grades, but there is a lack of randomised controlled trials regarding the use of ET versus continuous antibiotic prophylaxis in infants with high-grade VUR. This study aimed to determine whether high-grade VUR in infants can be treated with endoscopic injection and whether ET is superior to antibiotic prophylaxis in the treatment of VUR. This prospective, randomised, controlled, multicentre, 1-year follow-up trial comprised 77 infants (55 boys, 22 girls) <8 months of age with VUR grade 4-5 (n=30/n=47). Of the infants, 52 (68%) had bilateral VUR. Thirty-nine were randomised to antibiotic prophylaxis and 38 to ET (with prophylaxis until resolution). Voiding cystourethrogram, ultrasound, renal scintigraphy, and free voiding observation were performed at study entry and after 1 year to evaluate VUR grade, and renal and bladder function. VUR grade ≤2 was seen in 22 (59%) infants in the endoscopy group and eight (21%) in the prophylaxis group at follow-up (p=0.0014). The success rate in the endoscopy group was 100% in unilateral grade 4, falling to 31% in bilateral grade 5 (p=0.0094). Correspondingly, the results in the prophylaxis group were 40% in grade 4 down to 0% in bilateral grade 5 (p=0.037) (Table). Logistic regression analyses identified ET, VUR grade 4, unilaterality, and low residual urine at baseline as positive predictors of VUR down-grading to ≤2 (area under ROC curve 0.88). In four patients with reflux resolution after one injection, dilating reflux recurred at the 1-year follow-up. One patient had a UTI possibly related to ET. In our material four patients required re-implantation, of whom one was obstructive after injection. The opportunity to offer even small infants with high-grade VUR an alternative, minimally invasive treatment option is a great advance in paediatric urology. In this high-risk group, bilateral VUR grade 5 stands out with its poor bladder function and low chance of resolution. The recurrence rate of dilating VUR aftersuccessful ET is consistent with previous studies. The limitations are the relatively small number of patients and the short follow-up. High-grade VUR in infants can be treated with injection therapy and the resolution rate is higher than that of prophylaxis treatment. The complication rate is low and VUR grade 4, unilaterality, and low residual urine are favourable for the resolution and down-grading of VUR.

Efficacy of Six-Week Extended-Dose Nevirapine Varies by Infant Birth Weight with Greatest Relative Efficacy in Low Birth Weight Infants.

Latest World Health Organization guidelines recommend weight-based nevirapine prophylaxis for all HIV-exposed infants in resource-limited settings, yet low birth weight (LBW) infants (< 2500 g) have been understudied. Using data from the NIH-funded India six-week extended-dose nevirapine (SWEN) study, a randomized clinical trial of SWEN versus single-dose nevirapine (SD) for prevention of breast-milk HIV-1 transmission, we examined the relative impact of SWEN among 737 mother-infant pairs stratified by infant birth weight. Birth weight groups were defined as very LBW (VLBW) ≤ 2000 g, moderate LBW (MLBW) >2000 g and ≤ 2500 g, and normal birth weight (NBW) > 2500 g. Outcomes were HIV-1 infection, HIV-1 infection or death by 12 months, and severe adverse events (SAEs). The Kaplan-Meier method was used to estimate probability of efficacy outcomes in birth weight groups, and differential effects of SWEN by birth weight group were examined using Cox proportional hazards models adjusting for independent risk factors for HIV maternal-to-child transmission and significant covariates. Among 50 VLBW, 249 MLBW, and 433 NBW infants, 50% were randomized to SWEN; median gestational age was 36, 38 and 38 weeks, respectively; and there was no difference in breastfeeding duration (p = 0.99). Compared to SD: SWEN-treated VLBW had lower estimates of HIV-1 infection (13% vs. 38%, p = 0.004) and HIV-1 infection or death (13% vs. 41%, p = 0.002); SWEN-treated MLBW had lower estimated HIV-1 infection (13% vs. 17%, p = 0.042); and efficacy endpoints were similar by treatment arm in NBW. In multivariate analysis, SWEN was associated with reduced risk of HIV-1 infection or death by 83% (p = 0.03) in VLBW versus 45% (p = 0.05) in MLBW. SAE frequency was similar by treatment arm in VLBW (68% vs. 76%, p = 0.53) and MLBW (37% vs. 36%, p = 0.93). SWEN may safely increase HIV-free survival among HIV-exposed LBW infants with greatest protective advantage among infants ≤ 2000 g.

Consensus conference on the appropriateness of palivizumab prophylaxis in respiratory syncytial virus disease.

Respiratory syncytial virus infection represents a clinical burden among young children under 24 months. Palivizumab is the only drug licensed in Italy for the prevention of serious lower respiratory tract disease requiring hospitalization caused by respiratory syncytial virus in children at high risk. However recommendations for palivizumab prophylaxis are heterogeneous. Not all the published documents agree about the clinical indications of palivizumab; this could lead to different clinical practices and concerns about the appropriateness of prophylaxis. These issues and the lack of evidence about palivizumab prophylaxis efficacy in specific medical conditions brought on the idea of a consensus conference on the current recommendations for the management and prevention of bronchiolitis, in order to share useful indications. The goal was to perform a review of the evidence regarding the efficacy and the safety of palivizumab and give recommendations in order to harmonize its use. A structured and validated method to conduct the consensus process was adopted. The consensus conference recommends palivizumab prophylaxis in infants born before 29 weeks and younger than 12 months at the start of the epidemic season. According to evidence from literature and experts' opinion, palivizumab prophylaxis is not recommended in preterm infants of gestational age ≥29 weeks, without co-morbidity (i.e., cardiac, bronchopulmonary diseases). The experts identified some clinical rare conditions for which the decision of prophylaxis should be entrusted to the specialists. The evaluation of the appropriateness of palivizumab prophylaxis in the single patient should be documented by the specialists. Pediatr Pulmonol. 2016;51:1088-1096. © 2016 Wiley Periodicals, Inc.

HIV pre-exposure prophylaxis for women and infants prevents vaginal and oral HIV transmission in a preclinical model of HIV infection.

Approximately 1.5 million HIV-positive women become pregnant annually. Without treatment, up to 45% will transmit HIV to their infants, primarily through breastfeeding. These numbers highlight that HIV acquisition is a major health concern for women and children globally. They also emphasize the urgent need for novel approaches to prevent HIV acquisition that are safe, effective and convenient to use by women and children in places where they are most needed. 4'-Ethynyl-2-fluoro-2'-deoxyadenosine, a potent NRTI with low cytotoxicity, was administered orally to NOD/SCID/γc-/- mice and to bone marrow/liver/thymus (BLT) humanized mice, a preclinical model of HIV infection. HIV inhibitory activity in serum, cervicovaginal secretions and saliva was evaluated 4 h after administration. 4'-Ethynyl-2-fluoro-2'-deoxyadenosine's ability to prevent vaginal and oral HIV transmission was evaluated using highly relevant transmitted/founder viruses in BLT mice. Strong HIV inhibitory activity in serum, cervicovaginal secretions and saliva obtained from animals after a single oral dose of 4'-ethynyl-2-fluoro-2'-deoxyadenosine (10 mg/kg) demonstrated efficient drug penetration into relevant mucosal sites. A single daily oral dose of 4'-ethynyl-2-fluoro-2'-deoxyadenosine resulted in efficient prevention of vaginal and oral HIV transmission after multiple high-dose exposures to transmitted/founder viruses in BLT humanized mice. Our data demonstrated that 4'-ethynyl-2-fluoro-2'-deoxyadenosine efficiently prevents both vaginal and oral HIV transmission. Together with 4'-ethynyl-2-fluoro-2'-deoxyadenosine's relatively low toxicity and high potency against drug-resistant HIV strains, these data support further clinical development of 4'-ethynyl-2-fluoro-2'-deoxyadenosine as a potential pre-exposure prophylaxis agent to prevent HIV transmission in women and their infants.

Palivizumab Prophylaxis for Healthy Preterm Infants: More Data Supporting American Academy of Pediatrics Guidelines.

* Abbreviations: AAP — : American Academy of Pediatrics RSV — : respiratory syncytial virus As licensed by the US Food and Drug Administration, “palivizumab is indicated for the prevention of serious lower respiratory tract disease caused by respiratory syncytial virus (RSV) in pediatric patients at high risk of RSV disease”.1 The American Academy of Pediatrics (AAP) Committee on Infectious Diseases has endeavored to provide pediatricians and other health care providers with guidance for determining who is at high risk for RSV disease since palivizumab was first licensed in 1998.2 Over the years, evidence has accumulated regarding the risk of RSV hospitalization and the AAP guidance for palivizumab use has become more restrictive. The most recent recommendations,3 published in 2014, removed otherwise healthy preterm infants born at or after 29 weeks of gestation from the high-risk groups recommended to receive palivizumab prophylaxis. In this issue of Pediatrics , Farber et al4 provide data from nine Medicaid managed care health programs in Texas supporting the 2014 recommendation. The investigators evaluated the effect of palivizumab administration on hospitalization for bronchiolitis with or without an RSV diagnosis among healthy preterm infants born at 29 to 36 weeks of gestation during their first RSV season occurring in 2012, 2013, or 2014.4 These infants did not have conditions known to increase hospitalization rates for RSV, specifically, chronic lung disease of prematurity or congenital heart disease. Although the recommendations to limit use of palivizumab in healthy preterm infants were released in July 2014, the Texas Medicaid program did not fully adopt them until 2015. Interestingly, even though they would have qualified under previous guidelines, the majority of the infants in the Farber study4 evaluated from 2012 to 2014, did not have paid claims for palivizumab. Overall, … Address correspondence to Carrie L. Byington, MD, HA and Edna Benning Presidential Professor of Pediatrics, Associate Vice President for Faculty and Academic Affairs, University of Utah Health Sciences Center, 26 2000 East HSEB, Suite 5515, Salt Lake City, UT. E-mail: carrie.byington{at}hsc.utah.edu

Prevention of mother to child transmission of hepatitis B virus infection in Nigeria: A call to action

Background: Sub- Sahara Africa including Nigeria has the second largest global burden of chronic carriers of hepatitis B virus (HBV) infection after Asia. Mother-to-child transmission (MTCT) of HBV is the most commonroute of transmission in high endemic areas .MTCT of hepatitis B virus infection continues to occur despite the interventions of hepatitis B vaccinations and immunoglobulins in settings where it is practiced. Infants most at risk are those whose mothers have high HBV DNA viral loads and produce the protein HBeAg. Various Nigerian studies have reported high HBV infection rates as well as HBeAg positivity among pregnant women. These HBV infections usually occur intrapartum and rarely inutero. Mothers with HBeAg positivity known to be associated with higher HBV DNA viral loads have been linked with higher chances of MTCT as HBeAg is the only structural HBV protein that can cross into the placental circulation. In the absence of post exposure prophylaxis about 40 percent of infants delivered by HBV infected mothers could develop HBV infections, and about 25% of them may come down with chronic hepatitis and resulting possible complications including liver cirrhosis and hepatocellular cancer later in life. The prevention of transmission of retroviral infection from motherto- child has been a success story of the 21st century and such feat could be replicated for HBV infection. The standard PMTCT of HBV currently will comprise: timely prenatal screening, starting anti-viral therapy for pregnant women with HBeAg positivity and high viral load, infant postexposure prophylaxis and followup of infants of HBsAg positive mothers. There is no co-ordinated PMTCT of HBV programme in place in our setting despite the huge burden of the disease in Nigeria. Hence the need therefore to develop a home grown PMTCT programme of HBV to help tackle the burden of the disease in our country. An evidence based review of current best practice guidelines for the prevention of mother-to-child transmission of HBV for use in low and medium resource income settings with hepatitis B hyperendemicity will be quiet apt in this circumstance. This document therefore will be useful as a quick guide to Paediatricians, Obstetricians, Family Physicians, General Practice Doctors and other allied health workers charged with the care of pregnant mothers and their young children.Methods: Relevant literatures published in English language or translated into English were searched manually and electronically in PUBMED and SCOPUS for the period between 1990 and 2016 on the subject. Keywords searched included: epidemiology of HBV infection, MTCT of HBV, and its preventive strategies including prenatal screening, antiviral agents in pregnancy, infant post exposure prophylaxis and follow-up of infected children.Results: Over 35 scholarly articles on HBV epidemiology, MTCT, and preventive measures as well as follow –up models were retrieved and analyzed.Conclusion: Universal screening of all pregnant women for HBV infection is the most effective strategy for the prevention of MTCT of HBV, as effective preventive measures could be applied starting from pregnancy to delivery while infants of HBsAg positive mothers should receive timely post exposure prophylaxis and followed up for possible development of chronic hepatitis B infection.Key words: Prevention of mother to child transmission; Hepatitis B virus infection; Resource limited settings.

Fluconazole Prophylaxis for the Prevention of Candidiasis in Premature Infants: A Meta-analysis Using Patient-level Data.

Invasive candidiasis (IC) is an important cause of sepsis in premature infants and is associated with a high risk of death and neurodevelopmental impairment. Prevention of IC has become a major focus in very low birth weight infants, with fluconazole increasingly used as prophylaxis. We identified all randomized, placebo-controlled trials evaluating fluconazole prophylaxis in premature infants conducted in the United States. We obtained patient-level data from the study investigators and performed an aggregated analysis. The occurrence of each endpoint in infants who received prophylaxis with fluconazole vs placebo was compared. Endpoints evaluated were IC or death, IC, death, Candida colonization, and fluconazole resistance among tested isolates. Safety endpoints evaluated included clinical and laboratory parameters. Fluconazole prophylaxis reduced the odds of IC or death, IC, and Candida colonization during the drug exposure period compared with infants given placebo: odds ratios of 0.48 (95% confidence interval [CI], .30-.78), 0.20 (95% CI, .08-.51), and 0.28 (95% CI, .18-.41), respectively. The incidence of clinical and laboratory adverse events was similar for infants who received fluconazole compared with placebo. There was no statistically significant difference in the proportion of tested isolates that were resistant to fluconazole between the fluconazole and placebo groups. Fluconazole prophylaxis is effective and safe in reducing IC and Candida colonization in premature infants, and has no impact on resistance.

51 Microbiological impact of palivizumab prophylaxis in infants with cystic fibrosis

51 Microbiological impact of palivizumab prophylaxis in infants with cystic fibrosis

Comparison of First- and Second-Season Palivizumab Prophylaxis in Patients with Chronic Lung Disease (CLD) in the ‘Caress’ Database (2005-2014)

Abstract BACKGROUND: Respiratory syncytial virus (RSV) related hospitaliza-tion (RSVH) rates are 10-fold higher in infants with CLD compared with healthy term infants until 24 months of age. Current pediatric advisory guidelines recommend RSV prophylaxis for CLD infants &amp;lt; 2 years of age based on oxygen requirement for at least 28 days after birth during the first RSV season and those who continue to require chronic medical therapy for the management of CLD during the second season. OBJECTIVES: This study compared RSVH rates in CLD infants who received palivizumab during the first RSV season (FS) versus the second season (SS) in the Canadian Registry of Palivizumab (CARESS) database. DESIGN/METHODS: CARESS is a prospective registry of infants who received palivizumab at one of 32 sites across Canada during the 2005-2014 RSV seasons. Demographic data were collected at enrollment and respiratory-illness related hospitalization events were recorded monthly. Infants aged &amp;lt; 24 months with CLD were enrolled. RESULTS: 797 (55%) and 647 (45%) of 1444 CLD infants were prophy-laxed during FS and SS respectively (average age: 6.9 [FS] versus 13.6 [SS] months). SS infants had a lower gestational age [29.7 versus 31.3 weeks, F(1, 1440) = 29.9, p=&amp;lt;0.0005] and birth weight [1447 versus 1762 grams, F(1, 1436) = 29.3, p=&amp;lt;0.0005]. Infants prophylaxed in the SS also experienced more complicated neonatal courses with: prolonged respiratory support [63.4 versus 50.0 days, F(1, 1089) = 16.9, p=&amp;lt;0.0005], oxygen therapy [135.7 versus 74.8 days, F(1, 1155) = 97.4, p=&amp;lt;0.0005], and longer hospital stays [102.0 versus 72.0 days, F(1, 1369) = 62.1, p=&amp;lt;0.0005]. RSVH rates were 2.23% (FS) and 2.66% (SS). Cox regression adjusted for daycare attendance, multiple births, gestational age, birth weight and neonatal complications found no significant differences in the time to first RSVH between FS and SS infants (Hazard ratio: 0.96, 95% CI 0.37–2.52, p=0.94). CONCLUSION: SS infants who received RSV prophylaxis for CLD had a similar hazard of RSVH to those who only received palivizumab in the first year of life. The findings imply that FS and SS infants are correctly selected for RSV prophylaxis based on the stipulated criteria and their severity of illness and that SS infants are equally at risk for RSVH compared to FS infants.

Extended Pre-exposure Prophylaxis With Lopinavir-Ritonavir Versus Lamivudine to Prevent HIV-1 Transmission Through Breastfeeding Up to 50 Weeks in Infants in Africa (ANRS 12174)

(Abstracted from Lancet 2016;387:566–573) Worldwide, breast-feeding remains a key time during which mother-to-child transmission of human immunodeficiency virus type 1 (HIV-1) occurs. Interestingly, despite breast-feeding being recommended up to 12 months after birth, strategies to prevent postnatal mother-to-child transmission of HIV-1 in Africa, including infant prophylaxis, have never been assessed past 6 months of breast-feeding.

Prolonged Use of Proton Pump Inhibitors as Stricture Prophylaxis in Infants with Reconstructed Esophageal Atresia

Introduction Proton pump inhibitors (PPIs) are used as prophylaxis, guarding against anastomotic stricture (AS) in the aftermath of reconstructed esophageal atresia (EA). The incidence of stricture formation was studied in this setting, comparing outcomes of 3- and 12-month PPI prophylactic regimens. Patients and Methods Patient characteristics (gestational age, birth weight, prevalence of chromosomal aberrations, and other malformations), as well as rates of survival, AS formation, and required balloon dilation, were recorded in the following therapeutic subsets: (1) all infants undergoing primary surgical anastomosis for EA in years 2010-2014 and given postoperative PPI prophylaxis for 12 months and (2) all infants similarly treated for EA in years 2001-2009 but given postoperative PPI prophylaxis for 3 months only. Duration of follow-up was 1 year in each group. Results Patient characteristics and survival rates in 12-month (n = 33) and in 3-month (n = 30) treatment groups did not differ significantly. The prevalence of AS was 42%/43% in each group (12 months, 14/33; 3 months, 13/30; p = 1). Median number of dilations required was 3 (range, 1-9) per patient in each group (p = 0.69). Median age at initial dilation was 163 days and 63 days in 12- and 3-month groups, respectively (p = 0.04). Conclusion Development of AS in the first year after reconstruction of EA was not reduced by prolonged PPI prophylaxis (12 vs. 3 months), but initial balloon dilation procedures were performed later in infants who were treated longer.

Efficacy and safety of fluconazole prophylaxis in extremely low birth weight infants: multicenter pre-post cohort study.

BackgroundThere have been many studies supporting fluconazole prophylaxis in preterm infants for prevention of invasive fungal infections (IFIs). However, the routine use of fluconazole prophylaxis in neonatal intensive care units (NICUs) raises concerns with respect to resistance development, including the selection of resistant Candida species. We aimed to evaluate the efficacy and safety of fluconazole prophylaxis in extremely low birth weight (ELBW) infants.MethodsAn interventional pre-post cohort study at two tertiary NICUs was conducted. Data from two 5-year periods with and without fluconazole prophylaxis (Mar 2008–Feb 2013 and Mar 2003–Feb 2008) was compared. Prophylactic fluconazole was administered starting on the 3rd day at a dose of 3 mg/kg twice a week for 4 weeks during the prophylaxis period.ResultsThe fluconazole prophylaxis group consisted of 264 infants, and the non-prophylaxis group consisted of 159 infants. IFI occurred in a total of 19 neonates (4.7 %) during the 10-year study period. Fluconazole prophylaxis lower the fungal colonization rate significantly (59.1 % vs. 33.9 %, P <0.001). However, the incidence of IFIs in ELBW infants was not reduced after fluconazole prophylaxis (4.4 % vs. 5.5 %, P = 0.80). Rather, although the increase did not reach statistical significance, fluconazole prophylaxis tended to increase the incidence of invasive infections involving fluconazole-resistant C. parapsilosis (0 % vs. 41.7 %, P = 0.11).ConclusionsFluconazole prophylaxis was not efficacious in decreasing IFIs in ELBW infants. There is a need for targeting prophylaxis to greatest risk population and prospective studies to measure the long-term effect of fluconazole prophylaxis on the emergence of organisms with antifungal resistance.Electronic supplementary materialThe online version of this article (doi:10.1186/s12887-016-0605-y) contains supplementary material, which is available to authorized users.

Outcomes and linkage to chronic care of HIV exposed infants among health centers and hospitals in Amhara Region, Ethiopia: implications to prevention of mother-to-child transmission of HIV program: a cross sectional study.

IntroductionNumerous challenges exist in provision of prevention of mother-to-child transmission of HIV (PMTCT) such as linking HIV exposed infants (HEI) and their mothers to chronic cares services, and tackling loss to follow up. Limited evidence exists in Ethiopian setting that explains the persisting high HIV infection rate among HEIs and extent of linkage to chronic care. The study assessed the proportion of HIV infection; children linked to chronic care and determinants of HIV infection among HEI in Northern Ethiopia.MethodsThis institution-based cross-sectional study was conducted in health centers and hospitals of Amhara Region. A total of 484 HEI-mother pairs selected by multistage random sampling were included in the study. Data were collected from PMTCT and anti-retroviral therapy (ART) clinics using pre-tested and structured questionnaires. Quantitative data were entered in Epi Info version 7.0 and exported to SPSS 20.0 for analysis.ResultsA total of 484 mother-infant pairs with a response rate of 92.4% were included in the analysis. About 94.2% of infants and women were linked to chronic care follow-up sometime after the diagnosis. The proportion of HIV infection was 12.4%. Antenatal care attendance had a significant association with HIV infection among HEI (p < 0.0001). Delivering in health institution (p < 0.005), mode of delivery (p < 0.032), and provision of both infant (p < 0.0001) and maternal (p < 0.0001) prophylaxis showed a highly significant association with HIV infection among HIV exposed infants.ConclusionHealth facilities shall encourage antenatal care that increased institutional delivery, leads to timely initiation and high uptake of PMTCT to reduce the vertical transmission of HIV infection and meet national targets.

Cost Analysis of Fluconazole Prophylaxis for Prevention of Neonatal Invasive Candidiasis.

Fluconazole prophylaxis (FP) in premature infants is well studied and has been shown to decrease invasive candidiasis (ICs). IC in neonates has significant financial costs; determining the cost-benefit of FP may provide additional justification for targeting high-risk neonates. We aimed to determine the IC rate in premature infants at which FP is cost-beneficial. A decision tree cost-analysis model using cost of FP related to costs associated with IC was used. We searched PubMed for all papers that used intravenous FP and reported rates of IC in very low birth weight neonates. Average IC rates in those who received FP (2.0%; range, 0-6.1%) and in those who did not receive FP (9.2%; range, 0-20.5%) were used. Incremental hospital costs because of IC and for FP were retrieved from the literature. Sensitivity analysis was performed to determine the incremental cost of FP across the range of published IC rates. The average cost per patient attributed to IC in patients receiving FP was $785 versus $2617 in those not receiving FP. Sensitivity analysis demonstrates the rate of IC would need to be <2.8% for FP to lose its cost-benefit. In Monte Carlo simulation, targeting infants <1000 g would lead to $50,304,333 in cost savings per year in the United States. FP provides a cost-advantage across most IC rates seen in the youngest premature infants. Using a rate of 2.8% for their individual high-risk neonatal intensive care unit patients, providers can determine if FP is cost-beneficial in determining for whom to provide IC prophylaxis.

Implementation of American Academy of Pediatrics guidelines for palivizumab prophylaxis in a pediatric hospital.

One hospital's implementation of revised American Academy of Pediatrics (AAP) guidelines for palivizumab prophylaxis of respiratory syncytial virus (RSV) infection is described. Revised AAP guidelines for RSV prophylaxis in infants and young children at increased risk for RSV infection recommend that up to five doses of palivizumab be administered during the RSV season. The guidelines also recommend that inpatients not receive monthly palivizumab prophylaxis and that infants and young children eligible for prophylaxis during the RSV season receive a dose of palivizumab two or three days before discharge or promptly after discharge. To ensure compliance with the revised AAP guidelines, a 296-bed hospital implemented a quality-improvement project including (1) efforts by the antimicrobial stewardship pharmacist and the chief medical officer to notify and educate healthcare providers regarding institutional adoption of the guidelines, (2) reinforcement of guideline adherence by clinical pharmacists during daily bedside rounds and via prospective review of all palivizumab orders, and (3) a medication-use evaluation (MUE) to assess adherence to the guidelines. The MUE results showed that during the 2014-15 RSV season (after implementation of the practice changes), the number of palivizumab doses administered at the hospital declined by 56% from the previous RSV season, with 97% of doses administered for appropriate indications. Standardized, comprehensive guidelines with defined criteria for palivizumab prophylaxis of RSV infection resulted in $303,227 of cost savings without a discernible change in nosocomial transmission, or morbidity, or mortality. Hospital infection-control practices controlled nosocomial RSV transmission.

Commentary to “Barriers to participation in surgical randomized controlled trials in pediatric urology: A qualitative study of key stakeholder perspectives”

As pediatric urologists and active clinical investigators, it is with great interest that we read the recently published paper “Barriers to participation in surgical randomized controlled trials in pediatric urology: a qualitative study of key stakeholder perspectives” by Vemoulakonda and Jones [1] in the Journal. This is a unique, single-center study providing qualitative perspectives in the typically quantitatively dominated field of pediatric urology research. The authors provide an important basis to understand potential parental and healthcare provider barriers to enroll children in randomized controlled trials (RCTs). With these perceived obstacles in mind, investigators may be able to modify recruitment strategies in such a way that it may facilitate enrollment and increase participation. While this is undoubtedly a significant contribution to the literature, the authors base their study [1] on the assumption that pediatric urology surgical trials suffer from similarly low recruitment rates as those seen in adult surgical oncology trials [2]. Although reasonable, this simply may not always be the case. A clear example of high recruitment within pediatric urology surgical trials can be seen in the currently ongoing “Expertise-Based Randomized Controlled Trial of Scrotal Versus Inguinal Orchidopexy on Post-operative Pain” (NCT02158780), where, to date, 41 of 50 (82%) eligible patients have been recruited to participate [3]. Another example of reasonably high recruitment rate is seen in the challenging setting of a placebo control versus antibiotic prophylaxis for infants with highgrade prenatal hydronephrosis [4]. A 57% recruitment rate has been achieved thus far, providing further proof that RCTs are a feasible (and needed) study design in pediatric

A Test of Accuracy and Completeness in Data Flow Value Chain Within the Context of Early Infant Diagnosis of HIV Using Mixed Methods Approaches

Recent changes to Kenya’s early infant diagnosis (EID) testing algorithm have raised hope that the national goal of reducing perinatal HIV transmission rates to less than 5% can be attained. While programmatic efforts to reach this target are underway, obtaining complete and accurate data from clinical sites to track progress presents a major challenge. The purpose of this study was therefore to assess data completeness, accuracy and challenges in relation to routine EID data management in Kisumu East and Kisumu West Districts within Kisumu County, Kenya. Purposive sampling was used to select 23 active health facilities across the two districts disproportionate by partners. From the selected facilities a sampling frame of 192 patients was established and a sample size of 130 patient’s data selected. Accuracy and completeness were determined by computing sensitivity, specificity, and predictive values. Infant sex, Infant prophylaxis, Breastfeeding information, Entry point, and Test results were found to have registered replication completeness not significantly different from 99% replication at (p>0.05) as oppose to Sample code, Infant Age, Date of sample collection, and PMTCT prophylaxis were found to be significantly different from the 99% replication (p<0.05). On completeness; Sample code and date of sample collection registered completeness beyond the hypothesized value, implying they were complete as required. The remaining data elements including infant sex, infant age, infant prophylaxis, PMTCT prophylaxis, breastfeeding information and entry point were significantly lower than the hypothesized completeness value (p<0.0001) except for test results that had completeness score equal to 0.99. The study, therefore, concludes that despite the shortage of staffing and other challenges, personnel working in the data management system appear to be dedicated, informed and conscientious. However, this research suggests that there is a suboptimal use of the information for local action in certain areas. This assessment thus serves to enlighten policy-makers on the current state of the EID data management system in Kisumu East and West districts.

Guidelines for palivizumab prophylaxis in infants and young children at increased risk for respiratory syncytial virus infection in Saudi Arabia.

Respiratory syncytial virus (RSV) is a leading cause of serious seasonal lower respiratory tract infections (LRTI) in high-risk infants and children, with epidemics occurring annually in Saudi Arabia from October to March.Premature infants born at less than 29 weeks gestation with chronic lung disease or those with significant congenital heart disease who have RSV infection are more likely to be hospitalized and have increased morbidity and mortality. Palivizumab (Synagis®, Medimmune) is a humanized monoclonal antibody for the prevention of severe LRTI by RSV in high-risk children. The current use of Palivizumab in Saudi Arabia is not regulated and does not meet approved standards.This clinical practice policy statement was developed by the Ministry of Health and is supported by the National Immunization Technical Advisory Group (NITAG) in Saudi Arabia. It is based on available national and international data on the use of Palivizumab for the prevention of severe LRTI caused by RSV in high-risk pediatric patients. These guidelines were solicited and endorsed by two Saudi societies: The Neonatology and the Pediatric Infectious Diseases Societies.