[Show abstract][Hide abstract] ABSTRACT: To describe characteristics and outcomes of Jordanian newborns admitted to a large governmental neonatal intensive care unit (NICU).
Newborns born at the government hospital, Al Bashir, in Amman, Jordan were prospectively enrolled. The study focused on newborns admitted to the NICU and a retrospective chart review was performed. Abstraction included in-hospital mortality, antibiotic days, ventilation, oxygen use, and CRP levels. Rank sum and chi-squared tests were used to compare across outcomes. Logistic regression of hypothesized risk factors with death adjusted for gestational age.
Of the 5,466 neonates enrolled from 2/10-2/11, medical records were available for 321/378(84.9%) infants admitted to the NICU. The median gestational age was 36 weeks, median birth weight was 2.3 kg, and 28(8.7%) infants died. The two most common reasons for admission and mortality were respiratory distress syndrome and prematurity. Low Apgar scores and positive CRP were predictors of mortality. Risk factors associated with increased use of antibiotics, oxygen hood, and mechanical ventilation included lower gestational age and prematurity.
Infants admitted to the Jordanian NICU have significantly higher median gestational age and birth weights than in developed countries and were associated with significant morbidity and mortality. Continuations of global efforts to prevent prematurity are needed.
Global journal of health science 12/2015; 7(4). DOI:10.5539/gjhs.v7n4p217
[Show abstract][Hide abstract] ABSTRACT: Background and objectives:
Invasive pneumococcal disease (IPD) remains an important cause of illness in US children. We assessed the impact of introduction of the 13-valent pneumococcal conjugate vaccine (PCV13) on pediatric IPD rates, as well as changes in racial and regional differences in IPD, in Tennessee.
Data from active laboratory and population-based surveillance of IPD were used to compare IPD rates in the early-PCV7 (2001-2004), late-PCV7 (2005-2009), and post-PCV13 (2011-2012) eras. IPD rates were further stratified according to age, race, and region (east and middle-west TN).
Among children aged <2 years, IPD rates declined by 70% from 67 to 19 per 100 000 person-years in the early-PCV7 era and post-PCV13 era, respectively. Similar decreasing trends in IPD rates were observed in older children aged 2 to 4 years and 5 to 17 years. In the late-PCV7 era, IPD rates in children aged <2 years were higher in black children compared with white children (70 vs 43 per 100 000 person-years); however, these racial differences in IPD rates were no longer significant after PCV13 introduction. Before PCV13, IPD rates in children aged <2 years were also higher in east Tennessee compared with middle-west Tennessee (91 vs 45 per 100 000 person-years), but these differences were no longer significant in the post-PCV13 era.
PCV13 introduction led to substantial declines in childhood IPD rates and was associated with reduced regional and racial differences in IPD rates in Tennessee.
[Show abstract][Hide abstract] ABSTRACT: Background:
Using a multi-center, active surveillance network from two rotavirus seasons (2012 and 2013), we assessed the vaccine effectiveness of RV5 (RotaTeq) and RV1 (Rotarix) rotavirus vaccines in preventing rotavirus gastroenteritis hospitalizations and emergency department (ED) visits for numerous demographic and secular strata.
We enrolled children hospitalized or visiting the ED with acute gastroenteritis (AGE) for the 2012 and 2013 seasons at 7 medical institutions. Stool specimens were tested for rotavirus by enzyme immunoassay and genotyped, and rotavirus vaccination histories were compared for rotavirus-positive cases and rotavirus-negative AGE controls. We calculated the VE for preventing rotavirus associated hospitalizations and ED visits for each vaccine, stratified by vaccine dose, season, clinical setting, age, predominant genotype, and ethnicity.
RV5-specific VE analyses included 2,961 subjects, 402 rotavirus cases (14%) and 2,559 rotavirus-negative AGE controls. RV1-specific VE analyses included 904 subjects, 100 rotavirus cases (11%) and 804 rotavirus-negative AGE controls. Over the two rotavirus seasons, the VE for a complete 3-dose vaccination with RV5 was 80% (CI= 74% - 84%), and VE for a complete 2-dose vaccination with RV1 was 80% (CI= 68% - 88%).Statistically significant VE was observed for each year of life for which sufficient data allowed analysis (7 years for RV5 and 3 years for RV1). Both vaccines provided statistically significant genotype-specific protection against predominant circulating rotavirus strains.
In this large, geographically and demographically diverse sample of US children, we observed that RV5 and RV1 rotavirus vaccines each provided a lasting, and broadly heterologous protection against rotavirus gastroenteritis.
[Show abstract][Hide abstract] ABSTRACT: Importance:
A genetic polymorphism affecting FUT2 secretor status in approximately one-quarter of humans of European descent affects the expression of histo-blood group antigens on the mucosal epithelia of human respiratory, genitourinary, and digestive tracts. These histo-blood group antigens serve as host receptor sites necessary for attachment and infection of some pathogens, including norovirus.
We investigated whether an association exists between FUT2 secretor status and laboratory-confirmed rotavirus infections in US children.
Design, setting, and participants:
Multicenter case-control observational study involving active surveillance at 6 US pediatric medical institutions in the inpatient and emergency department clinical settings. We enrolled 1564 children younger than 5 years with acute gastroenteritis (diarrhea and/or vomiting) and 818 healthy controls frequency matched by age and month, from December 1, 2011, through March 31, 2013.
Main outcomes and measures:
Paired fecal-saliva specimens were tested for rotavirus and for secretor status. Comparisons were made between rotavirus test-positive cases and healthy controls stratified by ethnicity and vaccination status. Adjusted multivariable analyses assessed the preventive association of secretor status against severe rotavirus gastroenteritis.
One (0.5%) of 189 rotavirus test-positive cases was a nonsecretor, compared with 188 (23%) of 818 healthy control participants (P < .001). Healthy control participants of Hispanic ethnicity were significantly less likely to be nonsecretors (13%) compared with healthy children who were not of Hispanic ethnicity (25%) (P < .001). After controlling for vaccination and other factors, children with the nonsecretor FUT2 polymorphism appeared statistically protected (98% [95% CI, 84%-100%]) against severe rotavirus gastroenteritis.
Conclusions and relevance:
Severe rotavirus gastroenteritis was virtually absent among US children who had a genetic polymorphism that inactivates FUT2 expression on the intestinal epithelium. We observed a strong epidemiologic association among children with rotavirus gastroenteritis compared with healthy control participants. The exact cellular mechanism behind this epidemiologic association remains unclear, but evidence suggests that it may be rotavirus genotype specific. The lower prevalence of nonsecretors among Hispanic children may translate to an enhanced burden of rotavirus gastroenteritis among this group. Our findings may have bearing on our full understanding of rotavirus infections and the effects of vaccination in diverse populations.
[Show abstract][Hide abstract] ABSTRACT: Background:
Human metapneumovirus (HMPV) is a leading cause of acute respiratory tract infection (ARTI) in young children. Our objectives were to define HMPV epidemiology and circulating strains and determine markers of severe disease in Jordanian children.
We conducted a prospective study March 16, 2010-March 31, 2013using quantitative RT-PCR to determine the frequency of HMPV infection among children <2 years old admitted with fever and/or acute respiratory illness to a major government hospital in Amman, Jordan.
HMPV was present in 273/3168 (8.6%) of children presenting with ARTI. HMPV A2, B1, and B2, but not A1, were detected during the 3-year period. HMPV-infected children were older and more likely to be diagnosed with bronchopneumonia than HMPV-negative children. HMPV-infected children with lower respiratory tract infection (LRTI) had higher rates of cough and shortness of breath than children with LRTI infected with other or no identifiable viruses. Symptoms and severity were not different between children with HMPV only compared with HMPV co-infection. Children with HMPV subgroup A infection were more likely to require supplemental oxygen. In a multivariate analysis, HMPV subgroup A and age <6 months were independently associated with supplemental oxygen requirement.
HMPV is a leading cause of acute respiratory tract disease in Jordanian children <2 years old. HMPV A and young age were associated with severe disease. Ninety percent of HMPV-infected hospitalized children were full-term and otherwise healthy, in contrast to high-income nations; thus, factors contributing to disease severity likely vary depending on geographic and resource differences.
[Show abstract][Hide abstract] ABSTRACT: 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.
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.
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).
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.).
New England Journal of Medicine 03/2015; 372(10):933-43. DOI:10.1056/NEJMoa1404599 · 55.87 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background:
Norovirus is a leading cause of acute gastroenteritis (AGE). Noroviruses bind to gut histo-blood group antigens (HBGAs), but only 70%-80% of individuals have a functional copy of the FUT2 ("secretor") gene required for gut HBGA expression; these individuals are known as "secretors." Susceptibility to some noroviruses depends on FUT2 secretor status, but the population impact of this association is not established.
From December 2011 to November 2012, active AGE surveillance was performed at 6 geographically diverse pediatric sites in the United States. Case patients aged <5 years were recruited from emergency departments and inpatient units; age-matched healthy controls were recruited at well-child visits. Salivary DNA was collected to determine secretor status and genetic ancestry. Stool was tested for norovirus by real-time reverse transcription polymerase chain reaction. Norovirus genotype was then determined by sequencing.
Norovirus was detected in 302 of 1465 (21%) AGE cases and 52 of 826 (6%) healthy controls. Norovirus AGE cases were 2.8-fold more likely than norovirus-negative controls to be secretors (P < .001) in a logistic regression model adjusted for ancestry, age, site, and health insurance. Secretors comprised all 155 cases and 21 asymptomatic infections with the most prevalent norovirus, GII.4. Control children of Meso-American ancestry were more likely than children of European or African ancestry to be secretors (96% vs 74%; P < .001).
FUT2 status is associated with norovirus infection and varies by ancestry. GII.4 norovirus exclusively infected secretors. These findings are important to norovirus vaccine trials and design of agents that may block norovirus-HBGA binding.
[Show abstract][Hide abstract] ABSTRACT: Children who have undergone SOT mount a lower immune response after vaccination with TIV compared to healthy controls. HD or SD TIV in pediatric SOT was given to subjects 3–17 yr and at least six months post-transplant. Subjects were randomized 2:1 to receive either the HD (60 μg) or the SD (15 μg) TIV. Local and systemic reactions were solicited after each vaccination, and immune responses were measured before and after each vaccination. Thirty-eight subjects were enrolled. Mean age was 11.25 yr; 68% male, 45% renal, 26% heart, 21% liver, 5% lung, and 5% intestinal. Twenty-three subjects were given HD and 15 SD TIV. The median time since transplant receipt was 2.2 yr. No severe AEs or rejection was attributed to vaccination. The HD group reported more tenderness and local reactions, fatigue, and body ache when compared to the SD cohort, but these were considered mild and resolved within three days. Subjects in the HD group demonstrated a higher percentage of four-fold titer rise to H3N2 compared to the SD group. HD influenza vaccine was well tolerated and may have increased immunogenicity. A phase 2 trial is needed to confirm.
[Show abstract][Hide abstract] ABSTRACT: Children with cancer and HSCT recipients are at high risk for common viral infections. We sought to define the viral etiology of ARI and identify risk factors. Nasal wash samples were collected from pediatric hematology-oncology patients and HSCT recipients with ARI during the 2003-2005 winter seasons. Real-time RT-PCR was performed to detect Flu A, influenza B, RSV, PIV 1-3, human MPV, and HRV. HRV specimens were sequenced and genotyped. Seventy-eight samples from 62 children were included. Viruses were detected in 31 of 78 samples (40%). HRV were detected most frequently, in 16 (52%) including five HRVC; followed by seven (22%) RSV, five (16%) Flu A, four (13%) MPV, and two (6%) PIV2. There was a trend toward higher risk of viral infection for children in day care. Only 8% of the study children had received influenza vaccine. HRV, including the recently discovered HRVC, are an important cause of infection in pediatric oncology and HSCT patients. Molecular testing is superior to conventional methods and should be standard of care, as HRV are not detected by conventional methods.
[Show abstract][Hide abstract] ABSTRACT: Background: Children with acute gastroenteritis (AGE) present with vomiting, diarrhea, or both. The objective of our study was to compare the clinical presentation of viral causes of AGE when seeking medical care.
Methods: AGE surveillance for children ≥15 days and <18 years was performed at Vanderbilt Children's Hospital outpatient (OP) clinics and emergency department (ED). Stool specimens were tested by RT-PCR at the TN Department of Health central laboratory for norovirus (NoV) genogroups 1 and 2, sapovirus (SaV), and astrovirus (AsV). ELISA for rotavirus (RoV) VP6 antigen (Rotaclone@) was performed at Vanderbilt. AGE presentation was characterized as fever, vomiting only, diarrhea only, or both.
Results: From 12/1/12-11/30/13, 1217 AGE cases (763 [63%] ED, 454 [37%] OP) were enrolled, and 965 stool specimens (590 [61%] ED, 374 [39%] OP) were collected, with 52% males; 59% white, 36% black, and 38% Hispanic and a median age of 43 months. 422 (44%) patients had at least one virus detected, with 55 (13%) with more than one virus detected. Frequencies of viruses were: NoV G1, 15 (2%); NoV G2, 142(15%); NoV G1 and G2, 5 (<1%); RoV, 155 (16%); SaV, 117 (12%); and AsV, 49 (5%). One patient was excluded from the analysis because diarrhea status was unknown. Table 1 summarizes AGE presentation overall. Table 2 summarizes presentation by each virus, without co-detection.
Table 1. AGE presentation
AGE with stool
Table 2. AGE presentation by Virus, no co-detection
*p<0.05, fisher exact comparing study cohort
Cases of RoV and NoV were more likely to have both vomiting and diarrhea, but less frequently had symptoms of diarrhea alone. In contrast, isolated vomiting was less common among subjects who tested positive for RoV. Children with NoV were less likely to present with fever, while children with no detected virus were more likely to present with fever.
IDWeek 2014 Meeting of the Infectious Diseases Society of America; 10/2014
[Show abstract][Hide abstract] ABSTRACT: Background: Acute lower respiratory infections (ALRI) are a leading cause of death in children, but the role that viruses play in their etiology in Jordan and the Middle East is poorly characterized.
A prospective 3-year, year-round viral surveillance in children <2 years of age admitted with respiratory symptoms and/or fever at the Al-Bashir government hospital from 3/16/10 to 3/31/13 was conducted. Clinical and demographic data were collected. Nasal/throat swabs were obtained and were tested by real-time RT-PCR for respiratory syncytial virus (RSV), metapneumovirus (MPV), rhinovirus (HRV), influenza, and parainfluenza viruses 1, 2, and 3 (PIV1-3) and MERs-CoV.
Results: 3169 children were enrolled, virus detected in 81%. Mean age 3.5 months, 60% male. Most common ALRI diagnoses were bronchopneumonia (32%), bronchiolitis (17%), and pneumonia (12%). 284 (9%) were admitted to the ICU and only 31 (1%) died. Table 1 describes clinical presentation and viruses by these diagnoses. MERS-CoV was not detected. Figures 1 and 2 display the frequency of viruses and diagnoses over time, respectively.
Vitamin D level (median)
Abnormal chest x-ray
Conclusion: Viruses play a major role in ALRI in Jordanian children. Pneumonia was associated with higher morbidity and mortality; those children were younger, had lower vitamin D levels, and were more likely to require oxygen.
IDWeek 2014 Meeting of the Infectious Diseases Society of America; 10/2014
[Show abstract][Hide abstract] ABSTRACT: Given the resurgence of pertussis despite high vaccination rates with the diphtheria-tetanus-acellular pertussis (DTaP) vaccine, a better understanding of vaccine-induced immune responses to Bordetella pertussis (B. pertussis) is needed. We investigated the antibody, cell-mediated, and cytokine responses to B. pertussis antigens in children who received the primary vaccination series (at 2, 4, and 6 months) and first booster vaccination (at 15-18 months) with 5-component acellular pertussis (aP) vaccine. The majority of subjects demonstrated 4-fold increase in antibody titer to all four pertussis antigens (pertussis toxin[PT], pertactin[PRN], filamentous hemagglutinin[FHA], and fimbriae[FIM]) following the primary series and booster vaccination. Following the primary vaccine series, the majority of subjects (52-67%) mounted a positive T-cell proliferative response (stimulation index ≥3) to PT and PRN antigens, while few subjects (7-12%) mounted positive proliferative responses to FHA and FIM. One month after booster vaccination (age 16-19 months), our study revealed significant increase in IFN-γ production in response to PT and FIM antigens, significant increase in IL-2 production with PT, FHA, and PRN antigens, and lack of significant IL-4 secretion with any of the antigens. While previous reports documented a mixed Th1/Th2 or Th2-skewed response to DTaP vaccine in children, our data suggest that following the first DTaP booster, children aged 16-19 months have a cytokine profile consistent with a Th1 response, which is known to be essential for clearance of pertussis infection. To better define aP-induced immune responses following the booster vaccine, further studies are needed to assess cytokine responses pre- and post-booster in DTaP recipients.
[Show abstract][Hide abstract] ABSTRACT: Background:
As the influenza A H1N1 pandemic emerged in 2009, children were found to experience high morbidity and mortality and were prioritized for vaccination. This multicenter, randomized, double-blind, age-stratified trial assessed the safety and immunogenicity of inactivated influenza A(H1N1)pdm09 vaccine in healthy children aged 6 months to 17 years.
Children received 2 doses of approximately 15 or 30 µg hemagglutin antigen 21 days apart. Reactogenicity was assessed for 8 days after each dose, adverse events through day 42, and serious adverse events or new-onset chronic illnesses through day 201. Serum hemagglutination inhibition titers were measured on days 0 (prevaccination), 8, 21, 29 and 42.
A total of 583 children received the first dose and 571 received the second dose of vaccine. Vaccinations were generally well-tolerated and no related serious adverse events were observed. The 15 µg dosage elicited a seroprotective hemagglutination inhibition (≥ 1:40) in 20%, 47% and 93% of children in the 6-35 month, 3-9 year and 10-17 year age strata 21 days after dose 1 and in 78%, 82% and 98% of children 21 days after dose 2, respectively. The 30 µg vaccine dosage induced similar responses.
The inactivated influenza A(H1N1)pdm09 vaccine exhibited a favorable safety profile at both dosage levels. While a single 15 or 30 µg dose induced seroprotective antibody responses in most children 10-17 years of age, younger children required 2 doses, even when receiving dosages 4- to 6-fold higher than recommended. Well-tolerated vaccines are needed that induce immunity after a single dose for use in young children during influenza pandemics.
[Show abstract][Hide abstract] ABSTRACT: A multi-national prospective study of pediatric patients with invasive candidiasis between August 2007 and September 2012 was performed and included 441 infections. Variation in infecting Candida species and antifungals utilized was noted between US and non-US sites. Antifungal-associated adverse events were most common with polyene use.