Oral Valganciclovir Initiated Beyond 1 Month of Age as Treatment of Sensorineural Hearing Loss Caused by Congenital Cytomegalovirus Infection: A Randomized Clinical Trial.

OBJECTIVE: The objective of this study was to determine if valganciclovir initiated after 1 month of age improves congenital cytomegalovirus-associated sensorineural hearing loss. STUDY DESIGN: We conducted a randomized, double-blind, placebo-controlled phase 2 trial of 6 weeks of oral valganciclovir at US (n = 12) and UK (n = 9) sites. Patients of ages 1 month through 3 years with baseline sensorineural hearing loss were enrolled. The primary outcome was change in total ear hearing between baseline and study month 6. Secondary outcome measures included change in best ear hearing and reduction in cytomegalovirus viral load in blood, saliva, and urine. RESULTS: Of 54 participants enrolled, 35 were documented to have congenital cytomegalovirus infection and were randomized (active group: 17; placebo group: 18). Mean age at enrollment was 17.8 ± 15.8 months (valganciclovir) vs 19.5 ± 13.1 months (placebo). Twenty (76.9%) of the 26 ears from subjects in the active treatment group did not have worsening of hearing, compared with 27 (96.4%) of 28 ears from subjects in the placebo group (P = .09). All other comparisons of total ear or best ear hearing outcomes were also not statistically significant. Saliva and urine viral loads decreased significantly in the valganciclovir group but did not correlate with change in hearing outcome. CONCLUSIONS: In this randomized controlled trial, initiation of antiviral therapy beyond the first month of age did not improve hearing outcomes in children with congenital cytomegalovirus-associated sensorineural hearing loss. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT01649869.

Valganciclovir for symptomatic congenital cytomegalovirus disease.

BACKGROUND: The treatment of symptomatic congenital cytomegalovirus (CMV) disease with intravenous ganciclovir for 6 weeks has been shown to improve audiologic outcomes at 6 months, but the benefits wane over time. METHODS: We conducted a randomized, placebo-controlled trial of valganciclovir therapy in neonates with symptomatic congenital CMV disease, comparing 6 months of therapy with 6 weeks of therapy. The primary end point was the change in hearing in the better ear ("best-ear" hearing) from baseline to 6 months. Secondary end points included the change in hearing from baseline to follow-up at 12 and 24 months and neurodevelopmental outcomes, with each end point adjusted for central nervous system involvement at baseline. RESULTS: A total of 96 neonates underwent randomization, of whom 86 had follow-up data at 6 months that could be evaluated. Best-ear hearing at 6 months was similar in the 6-month group and the 6-week group (2 and 3 participants, respectively, had improvement; 36 and 37 had no change; and 5 and 3 had worsening; P=0.41). Total-ear hearing (hearing in one or both ears that could be evaluated) was more likely to be improved or to remain normal at 12 months in the 6-month group than in the 6-week group (73% vs. 57%, P=0.01). The benefit in total-ear hearing was maintained at 24 months (77% vs. 64%, P=0.04). At 24 months, the 6-month group, as compared with the 6-week group, had better neurodevelopmental scores on the Bayley Scales of Infant and Toddler Development, third edition, on the language-composite component (P=0.004) and on the receptive-communication scale (P=0.003). Grade 3 or 4 neutropenia occurred in 19% of the participants during the first 6 weeks. During the next 4.5 months of the study, grade 3 or 4 neutropenia occurred in 21% of the participants in the 6-month group and in 27% of those in the 6-week group (P=0.64). CONCLUSIONS: Treating symptomatic congenital CMV disease with valganciclovir for 6 months, as compared with 6 weeks, did not improve hearing in the short term but appeared to improve hearing and developmental outcomes modestly in the longer term. (Funded by the National Institute of Allergy and Infectious Diseases; ClinicalTrials.gov number, NCT00466817.).

Oral acyclovir suppression and neurodevelopment after neonatal herpes.

BACKGROUND: Poor neurodevelopmental outcomes and recurrences of cutaneous lesions remain unacceptably frequent among survivors of neonatal herpes simplex virus (HSV) disease. METHODS: We enrolled neonates with HSV disease in two parallel, identical, double-blind, placebo-controlled studies. Neonates with central nervous system (CNS) involvement were enrolled in one study, and neonates with skin, eye, and mouth involvement only were enrolled in the other. After completing a regimen of 14 to 21 days of parenteral acyclovir, the infants were randomly assigned to immediate acyclovir suppression (300 mg per square meter of body-surface area per dose orally, three times daily for 6 months) or placebo. Cutaneous recurrences were treated with open-label episodic therapy. RESULTS: A total of 74 neonates were enrolled--45 with CNS involvement and 29 with skin, eye, and mouth disease. The Mental Development Index of the Bayley Scales of Infant Development (in which scores range from 50 to 150, with a mean of 100 and with higher scores indicating better neurodevelopmental outcomes) was assessed in 28 of the 45 infants with CNS involvement (62%) at 12 months of age. After adjustment for covariates, infants with CNS involvement who had been randomly assigned to acyclovir suppression had significantly higher mean Bayley mental-development scores at 12 months than did infants randomly assigned to placebo (88.24 vs. 68.12, P=0.046). Overall, there was a trend toward more neutropenia in the acyclovir group than in the placebo group (P=0.09). CONCLUSIONS: Infants surviving neonatal HSV disease with CNS involvement had improved neurodevelopmental outcomes when they received suppressive therapy with oral acyclovir for 6 months. (Funded by the National Institute of Allergy and Infectious Diseases; CASG 103 and CASG 104 ClinicalTrials.gov numbers, NCT00031460 and NCT00031447, respectively.).

Effects of vaccine on rotavirus disease in the pediatric population.

PURPOSE OF REVIEW: Rotavirus infection is the most common cause of severe diarrhea disease in infants and young children worldwide and continues to have a major global impact on childhood morbidity and mortality. Two effective rotavirus vaccines are available and recommended for routine immunization of all infants. These vaccines have been introduced in both developed and developing countries. As rotavirus vaccines are implemented, studies have been undertaken that assess the effects of vaccination on rotavirus disease in children. This review summarizes the results of these studies. RECENT FINDINGS: Studies that assess health impact, indirect benefits, and strain changes after the introduction of rotavirus vaccine have been reported. In industrialized countries, rotavirus vaccination has led to dramatic drops in severe rotavirus-related hospitalizations and has reduced emergency room visits. Data from clinical trials in developing counties in Asia and Africa have demonstrated that rotavirus vaccines significantly reduce severe diarrhea episodes due to rotavirus. Herd (community) immunity has also been noted after routine rotavirus immunization in several countries. There have been no significant strain shifts or escape mutants noted since the introduction of rotavirus vaccines. SUMMARY: Two well tolerated and effective rotavirus vaccines have reduced the health burden of rotavirus gastroenteritis in both developed and developing countries.

Retropharyngeal involvement in multisystem inflammatory syndrome in children: Case report and review of literature.

A diagnosis of multisystem inflammatory syndrome in children should be made in the appropriate context and after ruling out other infectious causes. At the same time, clinicians should be diligent as the initial presentation can be unusual and the clinical picture can evolve over time. We report a case that was initially diagnosed as a retropharyngeal infection that did not improve on appropriate antimicrobial coverage. However, as the clinical picture evolved, the patient was found to have multisystem inflammatory syndrome in children and appropriately responded to immunomodulatory treatment. Pediatric infectious diseases practice has been significantly affected by the COVID-19 virus and multisystem inflammatory syndrome in children; data are still emerging as the pandemic evolves. We report this case and conduct literature review to expand the body of evidence about the association between multisystem inflammatory syndrome in children and retropharyngeal involvement.

Efficacy of the pentavalent rotavirus vaccine, RotaTeq® (RV5), between doses of a 3-dose series and with less than 3 doses (incomplete regimen).

Post-hoc analyses of the Rotavirus Efficacy and Safety Trial (REST) were conducted to determine whether the pentavalent rotavirus vaccine (RV5) confers early protection against rotavirus gastroenteritis (RVGE) before completion of the 3-dose regimen. To evaluate the efficacy of RV5 between doses in reducing the rates of RVGE-related hospitalizations and emergency department (ED) visits in infants who ultimately received all 3 doses of RV5/placebo, events occurring from 2 weeks after the first and second doses to receipt of the subsequent dose (Analysis A) and events occurring from 2 weeks after the first and second doses to 2 weeks after the subsequent dose (Analysis B) were analyzed. In Analysis A, RV5 reduced the rates of combined hospitalizations and ED visits for G1-G4 RVGE or RVGE regardless of serotype between doses 1 and 2 by 100% (95% confidence interval [CI]: 72-100%) or 82% (95% CI: 39-97%), respectively, and between doses 2 and 3, RV5 reduced the rates of combined hospitalizations and ED visits for G1-G4 RVGE or RVGE regardless of serotype by 91% (95% CI: 63-99%) or 84% (95% CI: 54-96%), respectively. Similar rate reductions were observed in Analysis B. These data suggest that RV5 provides a high level of protection between doses against hospitalizations and ED visits for RVGE starting as early as 14 days after the first dose.

Rotavirus vaccines: an overview.

Rotavirus infection is the most common cause of severe diarrhea disease in infants and young children worldwide and continues to have a major global impact on childhood morbidity and mortality. Vaccination is the only control measure likely to have a significant impact on the incidence of severe dehydrating rotavirus disease. In 1999, a highly efficacious rotavirus vaccine licensed in the United States, RotaShield, was withdrawn from the market after 14 months because of its association with intussusception. Two new live, oral, attenuated rotavirus vaccines were licensed in 2006: the pentavalent bovine-human reassortant vaccine (RotaTeq) and the monovalent human rotavirus vaccine (Rotarix). Both vaccines have demonstrated very good safety and efficacy profiles in large clinical trials in western industrialized countries and in Latin America. Careful surveillance has not revealed any increased risk of intussusception in the vaccinated groups with either vaccine. The new rotavirus vaccines are now introduced for routine use in a number of industrialized and developing countries. These new safe and effective rotavirus vaccines offer the best hope of reducing the toll of acute rotavirus gastroenteritis in both developed and developing countries.

It's Not Only Vaccine Hesitancy; It's Also Physician Hesitancy.

The danger of vaccine hesitancy is perhaps one of the most critical challenges we face as practitioners. This riveting narrative helps us find common ground and courage as it reaches into the hearts of those of us who have encountered parents who also want what's best for their child.

Safety and efficacy of a pentavalent human-bovine (WC3) reassortant rotavirus vaccine.

BACKGROUND: Rotavirus is a leading cause of childhood gastroenteritis and death worldwide. METHODS: We studied healthy infants approximately 6 to 12 weeks old who were randomly assigned to receive three oral doses of live pentavalent human-bovine (WC3 strain) reassortant rotavirus vaccine containing human serotypes G1, G2, G3, G4, and P[8] or placebo at 4-to-10-week intervals in a blinded fashion. Active surveillance was used to identify subjects with serious adverse and other events. RESULTS: The 34,035 infants in the vaccine group and 34,003 in the placebo group were monitored for serious adverse events. Intussusception occurred in 12 vaccine recipients and 15 placebo recipients within one year after the first dose including six vaccine recipients and five placebo recipients within 42 days after any dose (relative risk, 1.6; 95 percent confidence interval, 0.4 to 6.4). The vaccine reduced hospitalizations and emergency department visits related to G1-G4 rotavirus gastroenteritis occurring 14 or more days after the third dose by 94.5 percent (95 percent confidence interval, 91.2 to 96.6 percent). In a nested substudy, efficacy against any G1-G4 rotavirus gastroenteritis through the first full rotavirus season after vaccination was 74.0 percent (95 percent confidence interval, 66.8 to 79.9 percent); efficacy against severe gastroenteritis was 98.0 percent (95 percent confidence interval, 88.3 to 100 percent). The vaccine reduced clinic visits for G1-G4 rotavirus gastroenteritis by 86.0 percent (95 percent confidence interval, 73.9 to 92.5 percent). CONCLUSIONS: This vaccine was efficacious in preventing rotavirus gastroenteritis, decreasing severe disease and health care contacts. The risk of intussusception was similar in vaccine and placebo recipients. (ClinicalTrials.gov number, NCT00090233.)

Prevalence of group C rotavirus among children in Rhode Island, United States.

BACKGROUND: Group C rotavirus causes sporadic cases and outbreaks of acute diarrhea in humans but its burden as a cause of severe gastroenteritis in children remains unclear. OBJECTIVES: To investigate the epidemiology and burden of group C rotavirus gastroenteritis among children in Rhode Island, United States. STUDY DESIGN: Diarrhea stool specimens from 124 children < or =10 years of age were collected, screened for group C and A rotavirus by EIA specific for each group, and further examined by nested PCR and Southern hybridization using primers and probes specific to the VP7 gene of human group C rotavirus. Group C rotavirus-positive fecal specimens were also examined by EM. RESULTS: Rotavirus was detected in 73 (59.0%) of 124 fecal samples. These included 53 (42.7%) positive for group A, 5 (4.0%) for group C and 15 (12.1%) for both group A and C rotaviruses. Examination of group C-positive samples by EM revealed the presence of largely empty or damaged rotavirus-like particles. CONCLUSION: These findings indicate that group C rotavirus is an important cause or a contributing cause of diarrhea among infants and older children in Rhode Island, United States.

Nephrotoxicity With Vancomycin in the Pediatric Population: A Systematic Review and Meta-Analysis.

BACKGROUND: Vancomycin is frequently used to treat methicillin-resistant Staphylococcus aureus infections in pediatric patients. Vancomycin exposure may lead to an increase in frequency of nephrotoxicity. Our aim was to conduct a systematic review to describe predictors of nephrotoxicity associated with vancomycin, including documented trough concentrations ≥15 mg/L. We also aimed to use a meta-analysis to assess the impact of a vancomycin trough ≥15 mg/L on nephrotoxicity. METHODS: A literature search was performed using PubMed, Cochrane Library, Embase and Web of Sciences database. We included randomized clinical trials and observational studies evaluating the relationship between vancomycin troughs and nephrotoxicity in pediatric-age patients. Studies not measuring troughs or defining a different cut-off point than 15 mg/L were excluded. Data on age, exclusion criteria, nephrotoxicity definition, risk factors for nephrotoxicity and vancomycin trough levels were extracted from selected papers. RESULTS: Ten studies were identified for meta-analysis. All subjects had comparatively normal baseline serum creatinine values. Common risk factors identified included elevated (≥15 mg/L) trough levels, renal impairment, hypovolemia and concurrent use of nephrotoxic medications. Troughs ≥15 mg/L increased nephrotoxicity by 2.7-fold (odds ratio (OR), 2.71; 95% confidence interval: 1.82-4.05; I(2) = 40%; Q = 0.09). These odds were further increased among patients in the pediatric intensive care unit (OR, 3.61; 95% confidence interval: 1.21-10.74; I(2) = 45%; Q = 0.18). CONCLUSIONS: Though the rate of vancomycin-induced nephrotoxicity is increased in pediatric patients with higher vancomycin troughs, other factors such as intensive care unit admission, hypovolemia and concurrent nephrotoxic drug use appear to contribute to the development of nephrotoxicity.

Adverse Events Following Vaccination With Bivalent rLP2086 (Trumenba®): An Observational, Longitudinal Study During a College Outbreak and a Systematic Review.

BACKGROUND: In February 2015, two unlinked culture-confirmed cases of Neisseria meningitidis serogroup B (MenB) disease occurred at a local college in Rhode Island ("college X") within 3 days. This represented a 489-fold increase in the incidence of MenB disease, and an outbreak was declared. For the first time, bivalent rLP2086 (Trumenba) was selected as a mandatory intervention response. A mass vaccination clinic was coordinated, which provided a unique opportunity to collect safety data in a real-world population of college-age participants. Though the Advisory Committee on Immunization Practices recommends MenB vaccination for college-age individuals (16-23 year olds), there is limited quantifiable safety data available for this population. METHODS: The Dillman total design survey method was used. Adverse events of bivalent rLP2086 were solicited and quantified retrospectively 2-4 months following each dose of vaccine. Safety data from six clinical trials were used as comparison tools. RESULTS: The most commonly reported adverse event following vaccination was injection site pain. Reported rates of injection site pain, fatigue, myalgia, fever, and chills were similar than those reported in clinical trials. Reported rates of headache were lower than in clinical trials. CONCLUSIONS: This study is the first to examine adverse events of bivalent rLP2086 in a real-world setting where more than 90% of a college-age population was vaccinated.

Multifaceted but Invisible: Perceptions of the Value of a Pediatric Cognitive Specialty.

BACKGROUND: Systems for standardizing physician payment have been shown to undervalue cognitive clinical encounters. Because health care reform emphasizes value-based approaches, we need an understanding of the way pediatric cognitive specialties are used to contribute to the provision of high-value care. We sought to investigate how clinical and administrative stakeholders perceive the value of pediatric infectious disease (PID) specialists. METHODS: We conducted qualitative interviews with a purposive sample of physicians and administrators from 5 hospitals across the United States in which children are cared for. All interviews were transcribed and systematically analyzed for common themes. RESULTS: We interviewed 97 stakeholders. Analysis revealed the following 3 domains of value: clinical, organizational, and communicative. Clinically, PID specialists were perceived to be highly valuable in treating patients with unusual infections that respond poorly to therapy, in optimizing the use of antimicrobial agents and in serving as outpatient homes for complex patients. Respondents perceived that PID specialists facilitate communication with patients and their families, the health care team and the media. PID specialists were perceived to generate value by participating in systemwide activities, including antimicrobial stewardship and infection prevention. Despite this, much of the valuable work PID specialists perform is difficult to measure causing some administrative stakeholders to question how many PID specialists are necessary to achieve high-quality care. CONCLUSIONS: With our findings, we suggest that pediatric cognitive specialties contribute value in multiple ways to the health care delivery system. Many of these domains are difficult to capture by using current metrics, which may lead administrators to overlook valuable work and to under-allocate resources.

The integrated phase III safety profile of the pentavalent human-bovine (WC3) reassortant rotavirus vaccine.

BACKGROUND: Rotavirus gastroenteritis is a significant cause of morbidity and mortality. OBJECTIVE: To perform an integrated safety analysis of data from the Phase III studies of the pentavalent rotavirus vaccine (PRV). METHODS: Healthy 6- to 12-week-old infants received 3 doses of PRV or placebo at 4- to 10-week intervals in 3 Phase III, blinded, randomized, placebo-controlled trials. Active surveillance for serious adverse events (AE), including intussusception, was performed at 7, 14, and 42 days after each dose. Other AEs occurring within 42 days after each dose were documented on Vaccination Report Cards. Fecal shedding of vaccine-virus strains was evaluated by plaque assay and electropherotyping. RESULTS: Intussusception and other serious AEs were evaluated among 71,799 vaccinated subjects. Within 42 days after any dose, intussusception occurred among 6 PRV and 5 placebo recipients. All AEs were evaluated among 11 722 vaccinated subjects. Within the week following the first dose, the incidences of fever and irritability were similar among PRV and placebo recipients, although diarrhea and vomiting occurred more frequently among PRV recipients versus placebo recipients (10.4% vs. 9.1% and 6.7% vs. 5.4%, respectively). Fecal shedding of vaccine-virus strains occurred in 8.9% of 360 PRV recipients after the first dose. CONCLUSIONS: Across the 3 Phase III clinical trials, PRV was well tolerated, with no increased clinical risk of intussusception. Fecal shedding of vaccine-virus strains occurred infrequently and in low amounts, suggesting the risk of transmission is unlikely.

Adherence to Latent Tuberculosis Infection Treatment in a Population with a High Number of Refugee Children.

BACKGROUND: Refugee populations in the US have a higher reported prevalence of latent tuberculosis infection (LTBI). The objective of this study was to assess adherence to LTBI treatment in refugee and non-refugee children living in Rhode Island. METHODS: This was a retrospective review of LTBI patients seen in the Hasbro Pediatric Tuberculosis Clinic between August 2009 and September 2011. RESULTS: Of 120 patients with LTBI, 93% were foreign-born and 30% were refugees. Overall, 94 children (78.3%) completed therapy. Higher rates of treatment completion were seen among patients who were female, referred within the same hospital system, used an interpreter, and did not report side effects. Refugees attended more scheduled visits compared to non-refugees (p=0.019). CONCLUSIONS: Overall rates of completion of LTBI treatment were high in this population. Better adherence to clinic visits, likely due to the increased support and care coordination provided to the refugee children, improved treatment completion rates. [Full article available at http://rimed.org/rimedicaljournal-2017-02.asp].

Rapid response to a college outbreak of meningococcal serogroup B disease: Nation's first widespread use of bivalent rLP2086 vaccine.

OBJECTIVE: To outline the reasoning behind use of bivalent rLP2086 in a Rhode Island college meningococcal B disease outbreak, highlighting the timeline from outbreak declaration to vaccination clinic, emphasizing that these two time points are <3 days apart. PARTICIPANTS: Staff, faculty, and students at College X eligible for vaccination. METHODS: An outbreak response was initiated, advantages/disadvantages of available MenB vaccines were discussed, and a vaccination clinic was coordinated. RESULTS: Bivalent rLP2086 was chosen as the vaccination intervention. We achieved a 94% coverage rate for the first dose. To date, this intervention has prevented further cases of Neisseria meningitidis serogroup B disease at College X. CONCLUSIONS: The close, efficient collaboration of public health stakeholders and College X led 94% of the eligible population to be safely vaccinated with at least one dose of bivalent rLP2086. This outbreak marked the first time bivalent rLP2086 was effectively used as an intervention response.

Rhesus rotavirus vaccine effectiveness and factors associated with receipt of vaccine.

BACKGROUND: The rhesus rotavirus tetravalent vaccine (RotaShield) had an efficacy of 75%-100% in preventing severe rotavirus disease in prelicensure clinical trials. Before RotaShield's withdrawal because of reports of intussusception, there was an opportunity to evaluate the postlicensure effectiveness of the vaccine. The objective of this study was to determine the effectiveness of the RotaShield vaccine against rotavirus gastroenteritis requiring hospitalization and to evaluate factors associated with vaccine receipt. METHODS: Rotavirus cases were identified through active hospital-based rotavirus surveillance at 3 children's hospitals in Cincinnati, New Orleans and Providence. Cases were selected if they had been eligible for vaccine during the 10-month period when vaccine was available. Controls were matched to cases by date and county or state of birth. Immunization records were obtained from cases and controls to document receipt of RotaShield. Vaccine effectiveness (VE) was calculated for 1, 2, and 3 doses of vaccine with 95% confidence intervals (CI). RESULTS: For the 10-month period, 136 cases and 440 controls were enrolled. For 3 versus 0 doses of RotaShield, the VE was 100% (CI: 75%, 100%); for 2 versus 0 doses, the VE was 100% (CI: 62%, 100%), and for 1 versus 0 doses the VE was 89% (CI: 49%, 97%). RotaShield receipt was associated with white race, having more than 1 adult in the household, having insurance and having an older, more educated mother. CONCLUSIONS: This postlicensure study of RotaShield effectiveness found the vaccine to be highly effective in preventing rotavirus disease requiring hospitalization.

A case-control study to determine risk factors for hospitalization for rotavirus gastroenteritis in U.S. children.

OBJECTIVE: The objective of this case-control study nested within a surveillance study conducted at 3 hospitals (Cincinnati Children's Hospital Medical Center, Cincinnati, OH; Children's Hospital of New Orleans, New Orleans, LA; and Hasbro Children's Hospital, Providence, RI) was to identify risk factors for rotavirus gastroenteritis requiring hospitalization. PATIENTS: Cases were children < or =59 months of age who were admitted with acute gastroenteritis (AGE) and found to have rotavirus infection. Controls were selected from a birth certificate registry (Cincinnati and Providence) or a registry of patients from a large practice consortium in 11 locations (New Orleans). RESULTS: Three hundred forty-nine rotavirus-infected cases and 1242 control subjects were enrolled. Breast feeding was protective against hospitalization for rotavirus AGE for infants <6 months of age. (odds ratio [OR], 5.1; 95% confidence interval [CI], 1.2-13.2). Low-birth-weight (<2500 g) infants had increased risk for hospitalization even beyond the first few months of life (OR, 2.8; 95% CI, 1.6-5.0). Children in child care were more likely to be hospitalized for rotavirus AGE than those cared for at home, particularly those > or =24 months of age (OR, 3.0; 95% CI, 1.8-5.3). Other characteristics associated with rotavirus AGE hospitalization were children <24 months of age covered by Medicaid or without insurance (OR, 2.1; 95% CI, 1.4-3.2) and having another child in the house <24 months of age (OR, 1.6; 95% CI, 1.1-2.3). The data suggest that maternal age <25 years (OR, 1.4; 95% CI, 1.0-2.0) and a mother with less than a high school education (OR, 1.5; 95% CI, 1.0-2.3) may also increase risk of rotavirus hospitalization. CONCLUSION: There are socioeconomic and environmental factors and aspects of the child's medical and dietary history that identify children at risk for hospitalization with rotavirus AGE.

A Randomized, Double-Blind, Placebo-Controlled Trial of Pleconaril for the Treatment of Neonates With Enterovirus Sepsis.

BACKGROUND: Neonatal enterovirus sepsis has high mortality. Antiviral therapy is not available. METHODS: Neonates with suspected enterovirus sepsis (hepatitis, coagulopathy, and/or myocarditis) with onset at ≤15 days of life were randomized 2:1 to receive oral pleconaril or placebo for 7 days. Serial virologic (oropharynx, rectum, urine, serum), clinical, pharmacokinetic, and safety evaluations were performed. RESULTS: Sixty-one subjects were enrolled (43 treatment, 18 placebo), of whom 43 were confirmed enterovirus infected (31 treatment, 12 placebo). There was no difference in day 5 oropharyngeal culture positivity (primary endpoint; 0% in both groups). However, enterovirus-infected subjects in the treatment group became culture negative from all anatomic sites combined faster than placebo group subjects (median 4.0 versus 7.0 days, P = .08), and fewer subjects in the treatment group remained polymerase chain reaction (PCR)-positive from the oropharynx when last sampled (23% versus 58%, P = .02; median, 14.0 days). By intent to treat, 10/43 (23%) subjects in the treatment group and 8/18 (44%) in the placebo group died (P = .02 for 2-month survival difference); among enterovirus-confirmed subjects, 7/31 (23%) in the treatment group died versus 5/12 (42%) in the placebo group (P = .26). All pleconaril recipients attained concentrations greater than the IC90 after the first study day, but 38% were less than the IC90 during the first day of treatment. One subject in the treatment group and three in the placebo group had treatment-related adverse events. CONCLUSIONS: Shorter times to culture and PCR negativity and greater survival among pleconaril recipients support potential efficacy and warrant further evaluation.

Safety and immunogenicity of palivizumab (Synagis) administered for two seasons.

To evaluate the safety and immunogenicity of palivizumab, 55 children who received palivizumab in the IMpact-RSV trial received 5 monthly doses of 15 mg/kg palivizumab (Synagis) during the subsequent year. The single child with an antipalivizumab titer of >1/40 had no associated serious adverse events and had expected serum palivizumab trough concentrations. Second year palivizumab prophylaxis was safe and well-tolerated.