Natasha B Halasa

Vanderbilt University, Нашвилл, Michigan, United States

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Publications (59)295.39 Total impact

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    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
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    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 · 54.42 Impact Factor
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    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. Methods. From 12/2011 to 11/2012, active AGE surveillance was performed at six geographically diverse US pediatric sites. Cases under five 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 realtime RT-PCR. Norovirus genotype was then determined by sequencing. Results. Norovirus was detected in 302 (21%) of 1465 AGE cases and 52 (6%) of 826 healthy controls. Norovirus AGE cases were 2.8-fold more likely than norovirus-negative controls to be secretors (p<0.001) 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% versus 74%, p<0.001). Conclusions. 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.
    Clinical Infectious Diseases 03/2015; 60(11). DOI:10.1093/cid/civ165 · 9.42 Impact Factor
  • Natasha Halasa, Michael Green
    Pediatric Transplantation 12/2014; 18(8). DOI:10.1111/petr.12372 · 1.63 Impact Factor
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    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.
    Pediatric Transplantation 12/2014; 19(2). DOI:10.1111/petr.12419 · 1.63 Impact Factor
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    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.
    Pediatric Transplantation 11/2014; DOI:10.1111/petr.12383 · 1.63 Impact Factor
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    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 Vomiting Diarrhea Both Fever Total All AGE 342 (28%) 230 (19%) 644 (53%) 782/1211 (65%) 1216 AGE with stool 246 (26%) 191 (20%) 527 (55%) 625/960 (65%) 964 Table 2. AGE presentation by Virus, no co-detection NoV RoV SaV AsV No Virus Vomiting 38 (28%) 22 (18%)* 22 (26%) 7 (26%) 149 (28%) Diarrhea 8 (6%)* 11 (9%)* 13 (16%) 7 (26%) 144 (27%) Both 88 (66%)* 89 (73%)* 49 (58%) 13 (48%) 249 (46%)* Fever 69 (51%)* 77 (64%) 51 (61%) 21 (78%) 377 (70%)* TOTAL 134 122 84 27 542 *p<0.05, fisher exact comparing study cohort Conclusion: 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
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    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. Methods: 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. Table 1. Pneumonia N=394 Broncho-pneumonia N=1020 Bronchiolitis N=547 Total Cohort N=3169 Age (mean) 2.4 months 7.9 months 3.4 months 3.5 months Sex (male) 220 (56%) 604 (59%) 362 (66%) 1913 (60%) Vitamin D level (median) 11.7 ng/mL 20.6ng/mL 17.9ng/mL 16.5 ng/mL No PMH 342 (87%) 863 (85%) 519 (95%) 2848 (90%) Cough 358 (91%) 945 (93%) 526 (96%) 2366 (75%) Wheezing 250 (63%) 735 (72%) 483 (88%) 1757 (55%) Fever 201 (51%) 716 (70%) 173 (32%) 1763 (56%) Abnormal chest x-ray 381/390 (98%) 980/1009 (97%) 512/540 (95%) 2077/2963 (70%) Oxygen Use 209 (53%) 279 (28%) 215 (40%) 1013 (32%) MV 26 (7%) 37 (4%) 21 (4%) 111 (4%) ICU 80 (20%) 53 (5%) 32 (6%) 284 (9%) Death 10 (3%) 4 (0.003%) 1 (0.002%) 31 (1%) Virus RSV 225 (57%) 476 (47%) 374 (68%) 1397 (44%) HRV 153 (39%) 374 (37%) 215 (39%) 1238 (39%) MPV 37 (9%) 123(12%) 56 (10%) 273 (9%) Influenza 14 (4%) 50 (5%) 14 (3%) 123 (4%) PIV 17 (4%) 68 (7%) 23 (4%) 175 (6%) Adenovirus 68 (17%) 175 (15%) 62 (11%) 475 (15%) 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. Figures 1. Figure 2.
    IDWeek 2014 Meeting of the Infectious Diseases Society of America; 10/2014
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    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.
    Clinical and vaccine Immunology: CVI 09/2014; DOI:10.1128/CVI.00438-14 · 2.37 Impact Factor
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    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. Methods: Children received 2 doses of approximately 15 or 30 g 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. Results: 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 g 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 g vaccine dosage induced similar responses. Conclusions: The inactivated influenza A(H1N1) pdm09 vaccine exhibited a favorable safety profile at both dosage levels. While a single 15 or 30 g 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.
    The Pediatric Infectious Disease Journal 08/2014; 33(8):865-871. DOI:10.1097/INF.0000000000000329 · 3.14 Impact Factor
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    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.
    The Pediatric Infectious Disease Journal 06/2014; DOI:10.1097/INF.0000000000000431 · 3.14 Impact Factor
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    ABSTRACT: Although children with acute lymphoblastic leukemia (ALL) mount immune responses after vaccination with the trivalent influenza vaccine (TIV), these responses are lower compared to controls. Recently, a high dose (HD) TIV was found to increase the level of antibody response in elderly patients compared to the standard dose (SD) TIV. We hypothesized that the HD TIV would be well-tolerated and more immunogenic compared to the SD TIV in pediatric subjects with ALL. This was a randomized, double-blind, phase I safety trial comparing the HD to the SD TIV in children with ALL. Our secondary objective was immunogenicity. Subjects were randomized 2:1 to receive either the HD (60 µg) or the SD (15 µg) TIV. Local and systemic reactions were solicited, hemagglutinin inhibition titers to influenza virus antigens were measured, and monitoring labs were collected prior to and/or after each vaccination. Fifty subjects were enrolled (34 HD, 16 SD). Mean age was 8.5 years; 63% were male, and 80% were in maintenance therapy. There were no significant differences reported in local or systemic symptoms. No severe adverse events were attributed to vaccination. No significant differences between the HD and SD TIV groups were noted for immune responses. No differences were noted between the HD and SD TIV groups for solicited systemic and local reactions. Since this study was not powered for immunogenicity, a phase II trial is needed to determine the immunogenicity of HD versus SD TIV in the pediatric ALL population. Pediatr Blood Cancer © 2013 Wiley Periodicals, Inc.
    Pediatric Blood & Cancer 05/2014; 61(5). DOI:10.1002/pbc.24863 · 2.56 Impact Factor
  • Journal of Allergy and Clinical Immunology 02/2014; 133(2):AB13. DOI:10.1016/j.jaci.2013.12.073 · 11.25 Impact Factor
  • 01/2014; DOI:10.1093/jpids/piu061
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    ABSTRACT: Vitamin D deficiency is well recognized in selected Middle Eastern countries, but neonatal vitamin D status is not well studied in Jordan and other nearby countries. The aim of this study is to determine the prevalence of vitamin D deficiency in Jordanian newborns and risk factors associated with low levels. This is a prospective cohort study of newborn infants who were delivered at the Al Bashir Government Hospital in Amman, Jordan, from January 31, 2010, to January 27, 2011. Heel stick blood samples for 25-hydroxyvitamin D [25(OH)D] levels were obtained within 96 hours of birth. Maternal dress pattern, vitamin supplementation, smoke exposure during pregnancy, mode of delivery, gestational age, and birth weight were documented. Samples were obtained from 3,731 newborns. Median gestational age was 39 weeks, median birth weight was 3.1 kilograms, median maternal age was 27 years, and median newborn 25(OH)D level was 8.6nmol/L. A total of 3,512 newborns (94.1%) in this study were vitamin D deficient (< 50 nmol/L). Lower gestational age, maternal smoke exposure, and birth during winter months were associated with lower infant vitamin D levels, while vitamin D supplementation and time spent outside during pregnancy were associated with higher vitamin D levels. The prevalence of severely low vitamin D levels in newborn infants in Amman, Jordan, is substantial, even in newborns born during the spring and summer months. Vitamin D supplementation is needed in this population.
    Global journal of health science 01/2014; 6(1):162-71. DOI:10.5539/gjhs.v6n1p162
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    ABSTRACT: Hospitalized children < 2 years of age in Amman, Jordan, admitted for fever and/or respiratory symptoms, were tested for Middle East respiratory syndrome coronavirus (MERS-CoV): MERS-CoV by real-time RT-PCR (rRT-PCR). This was a prospective year-round viral surveillance study in children <2 years of age admitted with acute respiratory symptoms and/or fever from March 2010 to September 2012 and enrolled from a government-run hospital, Al-Bashir in Amman, Jordan. Clinical and demographic data, including antibiotic use, were collected. Combined nasal/throat swabs were collected, aliquoted, and frozen at -80°C. Specimen aliquots were shipped to Vanderbilt University and the Centers for Disease Control and Prevention (CDC), and tested by rRT-PCR for MERS-CoV. Of the 2433 subjects enrolled from 16 March 2010 to 10 September 2012, 2427 subjects had viral testing and clinical data. Of 1898 specimens prospectively tested for other viruses between 16 March 2010 and 18 March 2012, 474 samples did not have other common respiratory viruses detected. These samples were tested at CDC for MERS-CoV and all were negative by rRT-PCR for MERS-CoV. Of the remaining 531 samples, collected from 19 March 2012 to 10 September 2012 and tested at Vanderbilt, none were positive for MERS-CoV. Our negative findings from a large sample of young Jordanian children hospitalized with fever and/or respiratory symptoms suggest that MERS-CoV was not widely circulating in Amman, Jordan, during the 30-month period of prospective, active surveillance occurring before and after the first documented MERS-CoV outbreak in the Middle East region.
    Clinical Microbiology and Infection 10/2013; 20(7). DOI:10.1111/1469-0691.12438 · 5.20 Impact Factor
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    ABSTRACT: Background: Norovirus, rotavirus, and other enteric viruses are leading causes of acute gastroenteritis (AGE). The frequency of these viruses detected in asymptomatic individuals is poorly characterized. Methods: AGE surveillance, recruitment, and enrollment among children >15 days and <18 years were performed at Vanderbilt Children’s Hospital outpatient clinics (OP) and emergency department (ED). Davidson County residents enrolled with AGE were matched for age, race, and ethnicity to children without AGE (2 cases:1 control). Specimens were collected, aliquoted, and submitted to the TN Department of Health, where nucleic acid amplification assays for norovirus genogroups 1 (GI) and 2 (GII), sapovirus, and astrovirus were performed. Genotypes and strain identities of norovirus-positive specimens were ascertained by nucleotide sequence analysis using previously described CDC CaliciNet protocols. ELISA for rotavirus VP6 antigen (PremierTM Rotaclone@) was performed at Vanderbilt. Results: From 12/1/12-3/26/13, 404 AGE cases (245 ED, 159 OP) and 196 controls were enrolled. 244 (60%) of AGE cases & 40 (20%) of controls had at least one of the viruses detected (153 ED, 91 OP). Among AGE cases, rotavirus (109) was was most common, then norovirus G1 or G2 (87), sapovirus (53), & astrovirus (43). Among controls, norovirus GI or GII (22), sapovirus (13), astrovirus (10) & rotavirus (4) were detected. Both norovirus GI &GII were identified in four AGE cases. Sequence analysis of norovirus-positive specimens revealed GII.4 Sydney as the most common strain. AGE cases (n=404) Controls (n=196) P-value Rotavirus 109 (27%) 4 (2%) <0.001 Norovirus GI/GII 87 (22%) 22 (11%) 0.002 Sapovirus 53 (13%) 13 (7%) 0.017 Astrovirus 43 (12%) 10 (5%) 0.025 Conclusion: Collectively, rotavirus, norovirus, sapovirus, & astrovirus were detected in 60% of AGE cases; rotavirus was most common. Each agent was also detected in lower proportions in healthy controls. Further studies are warranted to understand the roles of these viruses in pediatric AGE and asymptomatic viral shedding. Additionally, rotavirus vaccination histories of study subjects and serotype identification of rotavirus-positive specimens will provide valuable information about the effectiveness of current rotavirus vaccines and possibly impact requirements of future vaccines.
    IDWeek 2013 Meeting of the Infectious Diseases Society of America; 10/2013
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    ABSTRACT: BACKGROUND:: Invasive meningococcal infections can be devastating. Substantial endotoxemia releases mature and immature neutrophils. Endothelial margination of mature neutrophils may increase the immature to total neutrophil ratio. These changes have not been previously well-described in invasive meningococcal disease. METHODS:: Using 2001-2011 data from the US Multicenter Meningococcal Surveillance Study, the diagnostic sensitivity and clinical correlates of white blood cell count (WBC), absolute neutrophil count (ANC), immature neutrophil count (INC), and immature-to-total neutrophil ratio (ITR) were evaluated alone and in combination at the time of diagnosis of invasive meningococcal disease. RESULTS:: 216 patients were evaluated: meningococcemia (65), meningitis (145), and other foci (6). ANC ≤ 1000/mm or ≥ 10,000/mm was present in 137 (63%), INC ≥ 500/mm in 170 (79%), and ITR ≥0.20 in 139 (64%). One or more of these 3 criteria were met in 204/216 (94%). Results were similar for meningococcemia and meningitis subgroups. All 13 cases with mildest disease met one or more of the 3 criteria. Eight children presented with absolute neutrophil counts <1000/mm: three of them died and a fourth required partial amputation in all four limbs. CONCLUSIONS:: Invasive meningococcal disease is characterized by striking abnormalities in absolute neutrophil count, immature neutrophil count, and/or immature-to-total neutrophil ratio. Neutropenia was associated with a poor prognosis. Notably, without immature neutrophil counts, 37% of cases would have been missed. Automated methods not measuring immature WBCs should be avoided when assessing febrile children. Serious infection should be considered when counts meet any of the three criteria.
    The Pediatric Infectious Disease Journal 06/2013; 32(10). DOI:10.1097/INF.0b013e31829e31f1 · 3.14 Impact Factor
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    ABSTRACT: BACKGROUND:: Invasive pneumococcal disease (IPD) rates decreased after 7-valent pneumococcal conjugate vaccine (PCV7) introduction in 2000. We assessed whether previously described decreases were sustained. METHODS:: Active laboratory-based surveillance identified IPD cases in five Tennessee Counties. For each case, clinical data were collected, and antibiotic susceptibility testing and serotyping were performed. Penicillin-resistance was defined as intermediate-or high-level resistance to penicillin. Serotypes were classified as PCV7, PCV13 (six additional serotypes not in PCV7), pneumococcal polysaccharide vaccine (PPV23, 11 additional serotypes not in PCV13, and non-vaccine serotypes. Total and penicillin-resistant IPD rates were calculated for persons <2, 2-14, and >15 years of age before (1998-99) and after (2001-2008) PCV7 introduction. RESULTS:: Annual IPD rates in children <2 years of age declined by 75% after PCV7 introduction (p<0.001). Annual IPD rates in children 2-14 years of age declined by 51% after PCV7 introduction (p<0.001). IPD rates in persons ≥15 of age years initially decreased 40% from 22 to 13 per 100,000 person-years (from 1998 through 2004), and then increased to 18 per 100,000 person-years in 2008. Both IPD and penicillin-resistant IPD PCV7 serotypes were almost completely eliminated in all age groups by 2008. During 2005-2008, 52.5%, 58%, and 38% of IPD serotypes in children <2, 2-14, and >15 years of age, respectively were the additional 6 serotypes in PCV13. CONCLUSIONS:: Overall, 9 years following PCV7 introduction both penicillin-susceptible and resistant IPD rates PCV7 serotypes have been nearly eliminated in Tennessee in all age groups. Total IPD rates remain reduced in children <15 years of age; whereas total IPD rates in persons ≥15 years of age have approached pre-PCV7 rates due to modest increases in non-vaccine serotypes.
    The Pediatric Infectious Disease Journal 01/2013; 32(6). DOI:10.1097/INF.0b013e318287fe0d · 3.14 Impact Factor
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    ABSTRACT: Background: Although children with ALL mount an immune response after vaccination with TIV, these responses are lower compared to controls. Methods: This was a randomized, double-blind, phase I safety & immunogenicity trial comparing HD to SD TIV in children with ALL aged 3-17 years, at least one month into chemotherapy and in 1stcomplete remission. Subjects were randomized 2:1 to receive either 0.5mL of HD (60ug per antigen) or SD (15ug per antigen) 2010-11 or 2011-12 TIV. Local & systemic reactions were collected for 7 days after each vaccination. HAI titers to influenza virus antigens as well as complete blood count, quantitative CD4, CD8, & CD19, & serum IgG were measured before & 28-35 days after vaccination, except year 1 no blood was drawn before dose 2. Results: 50 subjects were enrolled (20 year 1). Mean age was 8.25 years; 62% male; & 78% in maintenance therapy. 34 subjects were given HD & 16 SD (mean age 6.4 vs. 9.6 years), with 11 subjects receiving 2 doses (9 in HD & 2 in SD). The only significant difference between the HD & SD group was mean total CD19 count (10 vs 32, p=0.027). No SAEs were attributed to vaccination. Table 1. Safety parameters HD N=43 SD N=18 P value Any local 56% (24/43) 67% (12/18) 0.43 Any systemic 40% (17/43) 61% (11/18) 0.12 Temp >100.5 16% (7/43) 17% (3/18) 0.97 Table 2. Immunogenicity results HD Vac #1 SD Vac #1 P value HD Vac #2 SD Vac #2 P value A/California/7/09 H1N1 >1:40 100% (28/28) 100% (15/15) 1 100% (9/9) 100% (2/2) 1 >4-fold rise 32% (9/28) 57% (8/14) 0.12 78% (7/9) 100% (2/2) 0.46 A/Perth/16/2009 H3N2 >1:40 96% (27/28) 87% (13/15) 0.23 100% (9/9) 50% (1/2) 0.026 >4-fold rise 11% (3/28) 21% (3/14) 0.35 33% (3/9) 0% (0/2) 0.34 B/Brisbane/60/2008 >1:40 100% (28/28) 100% (15/15) 1 100% (9/9) 100% (2/2) 1 >4-fold rise 25% (7/28) 14% (2/14) 0.42 56% (5/9) 50% (1/2) 0.89 Table 3. GMT VISIT 1 VISIT 2 VISIT 3 HD SD HD SD HD SD A/California/7/09 H1N1 533 [361, 785] 611 [341, 1096] 780 [568, 1072] 1940 [1256, 2997] 1613 [712, 3651] 5120 [905, 28981] A/Perth/16/2009 H3N2 192 [96.8, 383] 231 [146.3, 365] 149 [82.5, 267] 221 [99.0, 494] 56.6 [2.72, 1175] 691.2 [165.38, 2889] B/Brisbane/60/2008 168 [106, 265] 170 [126, 230] 244 [155, 383] 306 [165, 566] 508 [189.6, 1361] 640 [79.1, 5178] Conclusion: No differences were noted between the HD and SD groups for solicited systemic and local reactions. A phase two trial is needed to determine the immunogenicity of HD versus SD in the population.
    IDWeek 2012 Meeting of the Infectious Diseases Society of America; 10/2012