Natasha B Halasa

Vanderbilt University, Nashville, Michigan, United States

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Publications (52)214.62 Total impact

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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: Background: Although pediatric IPD rates for TN have been reported, regional differences within TN have not been examined. We aimed to determine pediatric IPD rates in TN regions before and after PCV13 introduction (2010). Methods: Active population and laboratory-based surveillance identified IPD cases from 11 TN counties from 2001-2012. Counties were separated into East (2) and West (9). For each case, trained nurses collected clinical data, and the isolates were sent to CDC for serotyping. IPD incidence was calculated using U.S. census data and was expressed per 100,000 person-years. Groups were stratified by age: <2 and 2-18 years (yrs). Incidence rates were calculated for 3 time periods: Early-PCV7 (2001-2004), Late-PCV7 (2005-2009), and Post-PCV13 (2011-2012). The transition year 2010 was excluded and incidence rate ratios (IRR) were calculated to compare East and West TN IPD rates. Results: Table 1 shows IPD rates by serotype, region, age group, and time period. Figures 1 and 2 illustrate the decline in IPD rates by time period and region. Table 1. Annual IPD RATE per 100,000 EARLY-PCV7 ERA East <2 yrs West <2 yrs IRR (95% CI) East 2-18 yrs West 2-18 yrs IRR (95% CI) EARLY-PCV7 ERA PCV7 33.8 18.9 1.8 (1.0-2.3)* 2.6 3.7 1.4 (0.8-2.4) PCV13 23.5 11.4 2.1 (1.0-3.9)* 1.3 1.4 1.1 (0.4-2.5) Non-PCV 29.4 19.7 1.5 (0.8-2.5) 1.7 1.7 1.0 (0.5-2.1) Not-typed 19.1 7.5 2.6 (1.2-5.4)* 1.9 0.5 3.5 (1.4-9.0)* Total 106 57.5 1.8 (1.4-2.5)* 6.1 8.7 1.4 (1.0-2.0)* LATE-PCV7 ERA PCV7 1.1 1.2 0.9 (0.02-9.4) 0.9 0.3 3.6 (1.1-12)* PCV13 33.3 19.1 2.3 (1.5-3.5)* 2.3 2.7 0.9 (0.5-1.5) Not-typed 17.8 8.1 2.2 (1.1-4.2)* 1.8 0.8 2.2 (1.0-4.7)* Non-PCV 27.7 16.4 1.7 (1.0-2.8)* 2.3 1.9 1.2 (0.6-2.1) Total 91.0 44.8 2.0 (1.5-2.7)* 7.4 5.7 1.3 (0.9-1.8) POST-PCV13 ERA PCV7 0 0 NA 0.3 0 NA PCV13 5.3 3.6 1.5 (0.1-9.0) 1.3 0.9 1.4 (0.3-5.0) Not-typed 5.3 0.7 7.4 (0.4-434) 0.7 0.4 1.8 (0.2-1.0) Non-PCV 18.7 13.1 1.4 (0.5-3.6) 1.3 2.1 0.6 (0.2-1.8) Total 29.4 17.4 1.7 (0.8-3.6) 3.6 3.4 1.1 (0.5-2.1) *CI excludes 1 indicating significant differences Conclusion: Overall IPD rates Post-PCV13 decreased in all regions and age groups. IPD rates among children were significantly higher in East TN during the Early-PCV7 and Late-PCV7 period; however, those regional disparities were eliminated in the Post-PCV13 era.
    IDWeek 2014 Meeting of the Infectious Diseases Society of America; 10/2014
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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: 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; · 2.60 Impact Factor
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    ABSTRACT: 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.
    The Pediatric Infectious Disease Journal 08/2014; 33(8):865-871. · 3.57 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; · 3.57 Impact Factor
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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.
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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 11/2013; · 2.35 Impact Factor
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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; · 4.58 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; · 3.57 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; · 3.57 Impact Factor
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    ABSTRACT: Background: Although children who have undergone SOT 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 and immunogenicity trial comparing HD to SD TIV in pediatric SOT patients aged 3-17 years and at least six months after transplant. Subjects were randomized 2:1 to receive either 0.5mL of HD (60ug per antigen) or SD (15ug per antigen) 2011-2012 TIV. Local and systemic reactions were collected for seven days after each vaccination. HAI titers to influenza virus antigens were measured before and 28-42 days after vaccination. Complete blood count; quantitative CD4, CD8, and CD19; and serum IgG were also collected. Results: Thirty-eight subjects were enrolled. Mean age was 11.25 years; 68% male; 45% renal, 26% heart, 21% liver, 5% lung, and 5% intestinal. Twenty-three were given HD and 15 SD TIV. Average time since transplant was 7.4 years. No individuals had rejection associated with vaccination. Thirty-seven subjects were given one dose of vaccine. Table 1. Safety Parameters. Safety HD SD P value Any local 83% (19/23) 50% (7/14) 0.035 Any systemic 43% (10/23) 21% (3/14) 0.17 Temp >100.5 17% (4/23) 7% (1/14) 0.38 Table 2. Immunogenicity Results H1N1 A/California/7/09 H3N2 A/Perth/16/2009 H1N1 B/Brisbane/60/2008 HD SD P value HD SD P value HD SD P value >1:40 100% (23/23) 100% (15/15) 1 96% (22/23) 100% (15/15) 0.41 91% (21/23) 93% (14/15) 0.82 >4-fold rise 61% (14/23) 40% (6/15) 0.21 61% (14/23) 20% (3/15) 0.013 57% (13/23) 40% (6/15) 0.32 GMT Visit 1 52.5 [38.8, 71.0] 66.5 [45.7, 96.7] 54.1 [34.1, 85.7] 127.0 [71.8, 224.7] 59.2 [31.0, 113] 133.0 [59.8, 296] GMT Visit 2 184 [87.1, 388] 372 [203.6, 680] 230 [117, 452] 232 [100, 535] 230 [121, 435] 306 [139, 673] Conclusion: No differences were noted between the HD and SD groups for solicited systemic reactions. Local reactions were reported more in the HD group compared to the SD. Subjects in the HD group had a higher percentage of 4-fold rise to H3N2 compared to the SD group. These data support the need for a phase II trial.
    IDWeek 2012 Meeting of the Infectious Diseases Society of America; 10/2012
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    ABSTRACT: Background: The burden of disease attributable to parainfluenza viruses in hospitalized children in Amman, Jordan is unknown. Methods: We conducted a prospective year-round viral surveillance study in children <2 years of age admitted with respiratory symptoms and/or fever at the government-run hospital, Al-Basheer. Surveillance was conducted Sunday-Thursday from 3/16/2010-1/15/12. Clinical and demographic data including antibiotic use were collected. Nasal/throat swabs were collected, placed into lysis buffer, aliquoted, and frozen at -80°C. Specimen aliquots were shipped to Vanderbilt and tested by real-time RT-PCR for respiratory syncytial virus (RSV), metapneumovirus (HMPV), rhinovirus (HRV), influenza A and B, and parainfluenza viruses 1, 2, and 3 (PIV1-3). Results: A total of 1469 subjects were enrolled. The median age was 3.5 months, with 59% male, 10% had an underlying medical condition, 1% attended day care, 76% were exposed to smokers, 8% were admitted to the ICU, and 86% had a positive PCR for a virus. Ninety-seven (6%) tested positive for parainfluenza (30-PIV1, 9-PIV2, 58-PIV3) and 48% of these had co-detection with the following viruses: 33 HRV, 11 RSV, and 3 HMPV. The most common admission diagnoses were bronchopneumonia (39%), febrile neonate (23%), bronchiolitis (19%), and pneumonia (12%). Table 1 compares PIV1-3 positive to PIV1-3 negative subjects. A total of 29 (30%) required oxygen, nine were in the ICU, and seven required mechanical ventilation. Thirty-one (32%) were administered antibiotics prior to hospitalization and 86% during hospitalization. Table 1. PIV1-3 positive PIV1-3 negative p-value Age 4.8 months 3.4 months 0.01 Gender = Male 60%(58/97) 59%(815/1372) 0.81 Underlying medical condition 10%(10/97) 10%(131/1372) <0.001 Cough 78%(76/97) 70%(966/1372) 0.55 Fever 64%(62/97) 58%(802/1372) 0.95 Poor appetite 15%(15/97) 23%(319/1372) 0.14 Shortness of Breath 58%(56/97) 58%(790/1372) 0.2 Seizure 2%(2/97) 1%(11/1372) 0.65 Vomiting 14%(14/97) 18%(246/1372) 0.75 Diarrhea 12%(12/97) 11%(155/1372) 0.98 Conclusion: There was a significant burden of parainfluenza virus-associated hospitalizations in young children in Amman, Jordan. Compared to PIV1-3 negative subjects, PIV1-3 positive children were older and more likely to have an underlying medical condition.
    IDWeek 2012 Meeting of the Infectious Diseases Society of America; 10/2012
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    ABSTRACT: "Purpose " Reasons that newborns are admitted to the NICU in Amman, Jordan are not well-described in current literature. The purpose of this study was to describe a population of newborns admitted to the NICU and compare them to those newborns discharged to home. "Methods " Newborns born within 96 hours at Al-Bashir Hospital in Amman, Jordan were prospectively enrolled from February 2010 to July 2011. Demographic and clinical information were routinely collected for newborns and their mothers. Blood samples were obtained from infants by heel stick, placed on filter paper, and then sent to ZRT Laboratory for vitamin D [25(OH)D] measurement. We modeled the probability of NICU admission among newborns using logistic regression with splines. "Results " Among 5,404 newborns enrolled during this time period, 377 (7%) newborns were admitted to the NICU. The median gestational age of NICU infants was 37 weeks, median birth weight was 2.2 kg, 56.7% were male, 49.5% delivered by C-section (all non-elective), 71.1% were exposed to smoking (7.4% primary exposure), and 19.1% reported vitamin D supplementation. Median (IQR) vitamin D was 3.5 ng/ml (2.4-5.0). The most common reasons for admission include RDS (67%), prematurity (53%), low birth weight (11%), and sepsis (10%). Twenty-four babies (8.3%) died in the NICU. When comparing newborns discharged to home versus those admitted to the NICU, the following were strong predictors of NICU admission: gestational age of 36 weeks vs. 40 weeks, male sex, birth weight of 2.5 kg, delivery by C-section, vitamin D supplementation, and birth in the month of May (Table 1.). We failed to detect an association between other adjustment variables and NICU admission, including: maternal age, education, prenatal care, clothing practice, time spent outdoors, and secondary smoke exposure. Table 1. Predictors of NICU Admission Odds Ratio (95% CI) P-value Male 1.38 (1.03,1.83) 0.029 Gestational Age (weeks) 36 vs. 40 5.79 (4.20, 8.00) < 0.001 Birth Weight (kg) 2.5 kg vs. 3 kg 5.44 (4.45, 6.63) < 0.001 Cesarean Delivery vs. NSVD 2.39 (1.73, 3.29) < 0.001 Primary smoking exposure 0.57 (0.32, 1.00) 0.050 Any Vitamin D supplementation 1.82 (1.27, 2.61) 0.001 Birth in May vs. August 2010 2.27 (1.38, 3.73) <0.001 "Conclusions " Gestational age, birth weight, type of delivery, and month of birth were the strongest predictors of NICU admission at Al-Bashir hospital, which is consistent with other populations around the world; however, the median gestational age and birth weight are higher than developed countries.
    2012 American Academy of Pediatrics National Conference and Exhibition; 10/2012
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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
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    ABSTRACT: BACKGROUND:: Candida species are the third most common cause of pediatric healthcareassociated bloodstream infection in the United States and Europe. To our knowledge, this report from the International Pediatric Fungal Network is the largest prospective, multi-center observational study dedicated to pediatric and neonatal invasive candidiasis. METHODS:: From 2007-2011, we enrolled 196 pediatric and 25 neonatal patients with invasive candidiasis. RESULTS:: Non-albicans Candida species predominated in pediatric (56%) and neonatal (52%) age groups, yet C. albicans was the most common in both groups. Successful treatment responses were observed in pediatric (76%) and neonatal patients (92%). Infection with C. parapsilosis led to successful responses in pediatric (92%) and neonatal (100%) patients, while infection with C. glabrata was associated a lower successful outcome in pediatric patients (55%). The most commonly used primary antifungal therapies for pediatric invasive candidiasis were fluconazole (21%), liposomal amphotericin B (20%), and micafungin (18%). Outcome of pediatric invasive candidiasis was similar in response to polyenes (73%), triazoles (67%) and echinocandins (73%). The most commonly used primary antifungal therapies for neonatal invasive candidiasis were fluconazole (32%), caspofungin (24%), and liposomal amphotericin B (16%) and micafungin (8%). Outcomes of neonatal candidiasis by antifungal class again revealed similar response rates amongst the classes. CONCLUSIONS:: We found a predominance of non-albicans Candida infection in children and similar outcomes based on antifungal class used. This international collaborative study sets the foundation for large epidemiologic studies focusing on the unique features of neonatal and pediatric candidiasis and comparative studies of therapeutic interventions in these populations.
    The Pediatric Infectious Disease Journal 09/2012; · 3.57 Impact Factor
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    ABSTRACT: : To evaluate the prevalence of fungal infections (both pre-cannulation and post-cannulation) while on extracorporeal membrane oxygenation support and the associated morbidity and mortality. : Retrospective cohort study. : The Extracorporeal Life Support Organization database is an international voluntary registry of clinical data for patients placed on extracorporeal membrane oxygenation. The database was queried for all patients on extracorporeal membrane oxygenation from 1997 to 2009. Patient and extracorporeal membrane oxygenation data collected included age, support type, length of support, infection status and organism code, discharge status, complications, and component failures. Outcomes of interest were mortality, extracorporeal membrane oxygenation-related patient complications, and mechanical component failures. : From 1997 to 2009, there were 21,073 patients' extracorporeal membrane oxygenation runs analyzed of which 12,933 were in the neonatal group (0-30 days), 6,073 were in the pediatric group (31 days to <18 yrs old), and 2,067 were in the adult group (≥18 yrs). The prevalence of fungal infection during extracorporeal membrane oxygenation varied by age group and timing of infection and ranged from 0.04% to 5%. Fungal infections pre-extracorporeal membrane oxygenation and on-extracorporeal membrane oxygenation conferred a statistically significant higher relative risk of mortality for all age groups and varied by support type and timing of infection. Extracorporeal membrane oxygenation-related complications and component failures were not statistically significantly affected by infection status. : Fungal infection before or during extracorporeal membrane oxygenation increases the odds of mortality and the magnitude of this effect is dependent upon age-group and timing of infection. This increased mortality was not the result of increased patient or mechanical complications during extracorporeal membrane oxygenation. For patients with fungal infections pre-extracorporeal membrane oxygenation, 82%-89% demonstrated presumed clearance during extracorporeal membrane oxygenation. Although the risk of mortality increased with fungal infections, it does not appear that fungal infection before or during extracorporeal membrane oxygenation is a contraindication to initiation or continuation of support.
    Pediatric Critical Care Medicine 07/2012; 13(5):e288-93. · 2.35 Impact Factor
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    ABSTRACT: Background: Rule out sepsis (ROS) is a common reason for hospitalization of children worldwide. Methods: To determine characteristics of children diagnosed with ROS in Amman, Jordan, we conducted a 1 year prospective viral surveillance study in children <2 years of age admitted with respiratory symptoms and/or fever at the government-run hospital, Al-Basheer. Clinical and demographic data were collected. Nasal/throat swabs were collected, placed into lysis buffer, aliquoted, and frozen at -80°C. Specimen aliquots were shipped to Vanderbilt and tested by real-time RT-PCR for respiratory syncytial virus (RSV), metapneumovirus (HMPV), rhinovirus (HRV), influenza A and B, and parainfluenza virus 3 (PIV3). Results: A total of 732 subjects were enrolled. The median ages were 3.5 months, with 59% males. 63 (9%) had an underlying medical condition, 8 (1%) attended day care, 524 (72%) subjects were exposed to smokers, and 54 (8%) were admitted to the ICU. 190/732 (25.9%) of the subjects were diagnosed with ROS and 539 (74%) tested positive for a virus. Subjects diagnosed with ROS were less likely to present with cough, congestion, shortness of breath, (p<0.001, p=0.048, p<0.001) and more likely to present with vomiting and diarrhea (p<0.001, p<0.001). Subjects diagnosed with ROS had a lower mean and median age (1.5 vs. 7.1 and 1.2 vs. 5.5 months, p<0.01 for both) compared to subjects with other diagnoses. Their median length of stay at the hospital was longer, (6 vs 2 days, p<0.001), were less likely to require oxygen (14% vs. 30%, p<0.01), less likely to test positive for RSV (Table 1) but more likely to die in the hospital (2% vs. 0%, p=0.022). Table 1. Virus ROS N=190 (%) All other diagnoses N=542 (%) p-value RSV 50 (26%) 330 (61%) <0.01 hMPV 5 (3%) 22 (4%) 0.37 Influenza A 2 (1%) 12 (1%) 0.32 Influenza B 2 (1%) 8 (1) 0.67 PIV3 4 (2%) 14 (3%) 0.71 Conclusion: Children diagnosed with ROS presented with more severe illness, as indicated by their average length of hospital stay and increased mortality compared to other diagnoses. In addition, they presented less often with RSV. .
    Infectious Diseases Society of America 2011 Annual Meeting; 10/2011
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    ABSTRACT: Purpose: To determine the prevalence of vitamin D deficiency in selected Jordanian full-term newborns and risk factors associated with low levels. Methods: Newborn infants were prospectively enrolled during spring and summer months during 2010. Newborns >37 weeks of age and those born within 96 hours at Al Bashir Hospital in Amman, Jordan were included. Demographic information for newborns and their mothers were collected including child’s birth date, child’s birth weight, average daily number of hours mother spends outdoors, mother’s clothing practice, and smoke exposure. Blood samples were obtained from infants by heel stick, placed on filter paper, and then sent to ZRT Laboratory for vitamin D [25(OH)D] measurement. Results: A total of 1,692 (825 males and 867 females) out of 2,009 newborns enrolled met inclusion criteria. The mean gestational age was 39.86 weeks, with a median birth weight of 3.2 kg. The mean age of the mothers was 27.41 years. The majority (87.6%) of mothers wore only a head scarf, 11.8% of mothers were fully covered, and 0.6% wore traditional European clothing. The median 25(OH)D level for the newborns was 3.0 ng/mL, and the mean 25(OH)D was 3.87 ng/mL. All but 3 newborns in this study were vitamin D deficient. Five percent of all mothers smoked cigarettes during pregnancy, 1% of mothers smoked nargila during pregnancy, and 73% of mothers reported smoke exposure in the household during pregnancy. Younger maternal age, greater number of reported months of vitamin D supplementation, and birth during summer months were associated with higher newborn vitamin D levels (p=0.02, p=0.023, and p=0.006, respectively). Conclusion: The prevalence of extremely low vitamin D levels in newborn infants in Amman, Jordan is substantial, despite these newborns being born during the spring and summer months. Vitamin D supplementation is needed in this population.
    2011 American Academy of Pediatrics National Conference and Exhibition; 10/2011

Publication Stats

911 Citations
214.62 Total Impact Points

Institutions

  • 2002–2014
    • Vanderbilt University
      • • Division of Infectious Diseases
      • • Department of Pediatrics
      • • Department of Medicine
      Nashville, Michigan, United States
  • 2013
    • University of Utah
      • Department of Pediatrics
      Salt Lake City, Utah, United States
  • 2010–2013
    • University of Jordan
      `Ammān, Amman, Jordan