- Pediatric Infectious Diseases
Clinical Associate Professor, Pediatrics - Infectious Diseases
Residency: Mattel Children's Hospital at UCLA (2005) CA
Board Certification: American Board of Pediatrics, Pediatric Infectious Diseases (2009)
Fellowship: UCLA Mattel Children's Hospital Pediatric Infectious Disease Prgm (2008) CA
Board Certification: American Board of Pediatrics, Pediatrics (2005)
Medical Education: Columbia University College of Physicians and Surgeons (2002) NY
Understanding Variation in Rotavirus Vaccine Effectiveness Estimates in the United States: The Role of Rotavirus Activity and Diagnostic Misclassification.
Epidemiology (Cambridge, Mass.)
BACKGROUND: Estimates of rotavirus vaccine effectiveness (VE) in the U.S. appear higher in years with more rotavirus activity. We hypothesized rotavirus VE is constant over time but appears to vary as a function of temporal variation in local rotavirus cases and/or misclassified diagnoses.METHODS: We analyzed 6 years of data from eight U.S. surveillance sites on 8-59-month olds with acute gastroenteritis symptoms. Children's stool samples were tested via enzyme immunoassay (EIA); rotavirus-positive results were confirmed with molecular testing at the US Centers for Disease Control and Prevention (CDC). We defined rotavirus gastroenteritis cases by either positive on-site EIA results alone or positive EIA with CDC confirmation. For each case definition, we estimated VE against any rotavirus gastroenteritis, moderate-to-severe disease, and hospitalization using two mixed-effect regression models: the first including year plus a year-vaccination interaction, and the second including annual percent of rotavirus positive tests plus a percent positive-vaccination interaction. We used multiple overimputation to bias-adjust for misclassification of cases defined by positive EIA alone.RESULTS: Estimates of annual rotavirus VE against all outcomes fluctuated temporally, particularly when we defined cases by on-site EIA alone and used a year-vaccination interaction. Use of confirmatory testing to define cases reduced, but did not eliminate, fluctuations. Temporal fluctuations in VE estimates further attenuated when we used a percent positive-vaccination interaction. Fluctuations persisted until bias-adjustment for diagnostic misclassification.CONCLUSIONS: Both controlling for time-varying rotavirus activity and bias-adjusting for diagnostic misclassification are critical for estimating the most valid annual rotavirus VE.
View details for DOI 10.1097/EDE.0000000000001501
View details for PubMedID 35583516
Infectious Causes of Acute Gastroenteritis in US Children Undergoing Allogeneic Hematopoietic Cell Transplant: A Longitudinal, Multicenter Study.
Journal of the Pediatric Infectious Diseases Society
2020; 9 (4): 421-427
Acute gastroenteritis (AGE) in hematopoietic cell transplant (HCT) patients causes significant morbidity and mortality. Data regarding the longitudinal assessment of infectious pathogens during symptomatic AGE and asymptomatic periods, particularly in children, are limited. We investigated the prevalence of AGE-associated infectious pathogens in children undergoing allogeneic HCT.From March 2015 through May 2016, 31 pediatric patients at 4 US children's hospitals were enrolled and had stool collected weekly from pre-HCT through 100 days post-HCT for infectious AGE pathogens by molecular testing. Demographics, clinical symptoms, antimicrobials, vaccination history, and outcomes were manually abstracted from the medical record into a standardized case report form.We identified a pathogen in 18% (38/206) of samples, with many detections occurring during asymptomatic periods. Clostridioides difficile was the most commonly detected pathogen in 39% (15/38) of positive specimens, although only 20% (3/15) of C. difficile-positive specimens were obtained from children with diarrhea. Detection of sapovirus, in 21% (8/38) of pathogen-positive specimens, was commonly associated with AGE, with 87.5% of specimens obtained during symptomatic periods. Norovirus was not detected, and rotavirus was detected infrequently. Prolonged shedding of infectious pathogens was rare.This multicenter, prospective, longitudinal study suggests that the epidemiology of AGE pathogens identified from allogeneic HCT patients may be changing. Previously reported viruses, such as rotavirus and norovirus, may be less common due to widespread vaccination and institution of infection control precautions, and emerging viruses such as sapoviruses may be increasingly recognized due to the use of molecular diagnostics.
View details for DOI 10.1093/jpids/piz063
View details for PubMedID 31550350
Association of Rotavirus Vaccination With Inpatient and Emergency Department Visits Among Children Seeking Care for Acute Gastroenteritis, 2010-2016.
JAMA network open
2019; 2 (9): e1912242
Rotavirus vaccines have been recommended for universal US infant immunization for more than 10 years, and understanding their effectiveness is key to the continued success of the US rotavirus vaccine immunization program.To assess the association of RotaTeq (RV5) and Rotarix (RV1) with inpatient and emergency department (ED) visits for rotavirus infection.This case-control vaccine effectiveness study was performed at inpatient and ED clinical settings in 7 US pediatric medical institutions from November 1, 2009, through June 30, 2016. Children younger than 5 years seeking medical care for acute gastroenteritis were enrolled. Clinical and epidemiologic data, vaccination verification, and results of stool sample tests for laboratory-confirmed rotavirus were collected. Data were analyzed from November 1, 2009, through June 30, 2016.Rotavirus vaccine effectiveness for preventing rotavirus-associated inpatient and ED visits over time for each licensed vaccine, stratified by clinical severity and age.Among the 10 813 children included (5927 boys [54.8%] and 4886 girls [45.2%]; median [range] age, 21 [8-59] months), RV5 and RV1 analyses found that compared with controls, rotavirus-positive cases were more often white (RV5, 535 [62.2%] vs 3310 [57.7%]; RV1, 163 [43.1%] vs 864 [35.1%]), privately insured (RV5, 620 [72.1%] vs 4388 [76.5%]; RV1, 305 [80.7%] vs 2140 [87.0%]), and older (median [range] age for RV5, 26 [8-59] months vs 21 [8-59] months; median [range] age for RV1, 22 [8-59] months vs 19 [8-59] months) but did not differ by sex. Among 1193 rotavirus-positive cases and 9620 rotavirus-negative controls, at least 1 dose of any rotavirus vaccine was 82% (95% CI, 77%-86%) protective against rotavirus-associated inpatient visits and 75% (95% CI, 71%-79%) protective against rotavirus-associated ED visits. No statistically significant difference during this 7-year period was observed for either rotavirus vaccine. Vaccine effectiveness against inpatient and ED visits was 81% (95% CI, 78%-84%) for RV5 (3 doses) and 78% (95% CI, 72%-82%) for RV1 (2 doses) among the study population. A mixed course of both vaccines provided 86% (95% CI, 74%-93%) protection. Rotavirus patients who were not vaccinated had severe infections 4 times more often than those who were vaccinated (74 of 426 [17.4%] vs 28 of 605 [4.6%]; P < .001), and any dose of rotavirus vaccine was 65% (95% CI, 56%-73%) effective against mild infections, 81% (95% CI, 76%-84%) against moderate infections, and 91% (95% CI, 85%-95%) against severe infections.Evidence from this large postlicensure study of rotavirus vaccine performance in the United States from 2010 to 2016 suggests that RV5 and RV1 rotavirus vaccines continue to perform well, particularly in preventing inpatient visits and severe infections and among younger children.
View details for DOI 10.1001/jamanetworkopen.2019.12242
View details for PubMedID 31560386
View details for PubMedCentralID PMC6777243
An Observational Study of Severe Pertussis in 100 Infants 120 Days of Age
PEDIATRIC INFECTIOUS DISEASE JOURNAL
2018; 37 (3): 202–5
Pertussis in young infants is a unique, severe, afebrile, cough illness that is frequently fatal.All pertussis cases ≤120 days of age admitted to a pediatric intensive care unit in California between October 1, 2013, and April 25, 2015, were evaluated.Of 100 pertussis patients ≤120 days of age admitted to pediatric intensive care unit, there were 5 deaths. The white blood cell counts in the fatal cases were significantly higher than in the nonfatal cases. Thirty-four percent of patients were intubated, 18% received inotropic and/or vasoactive support, 22% received steroid, 4% received extracorporal membrane oxygenation, and 3% underwent exchange blood transfusion. The median age at the time of illness onset in the patients who died was 23 days.These data, as well as data from previous California studies, suggest updated strategies for the management of severe pertussis. These include perform serial white blood cell counts, treat all presumptive cases with azithromycin, evaluate for pulmonary hypertension, intubate and administer oxygen for apneic episodes and administer inotropic/vasoactive agents for cardiogenic shock. Do not administer steroids or nitric oxide. Criteria for exchange blood transfusion therapy for leukocytosis with lymphocytosis are suggested.
View details for DOI 10.1097/INF.0000000000001710
View details for Web of Science ID 000426088200010
View details for PubMedID 28737623
Creating the Subspecialty Pediatrics Investigator Network
JOURNAL OF PEDIATRICS
2018; 192: 3-+
View details for DOI 10.1016/j.jpeds.2017.09.079
View details for Web of Science ID 000423353900001
View details for PubMedID 29246355
Rotavirus Strain Trends During the Postlicensure Vaccine Era: United States, 2008-2013.
The Journal of infectious diseases
2016; 214 (5): 732-8
Group A rotaviruses (RVA) are a significant cause of pediatric gastroenteritis worldwide. The New Vaccine Surveillance Network (NVSN) has conducted active surveillance for RVA at pediatric hospitals and emergency departments at 3-7 geographically diverse sites in the United States since 2006.Over 6 consecutive years, from 2008 to 2013, 1523 samples from NVSN sites that were tested positive by a Rotaclone enzyme immunoassay were submitted to the Centers for Disease Control and Prevention for genotyping.In the 2009, 2010, and 2011 seasons, genotype G3P was the predominant genotype throughout the network, with a 46%-84% prevalence. In the 2012 season, G12P replaced G3P as the most common genotype, with a 70% prevalence, and this trend persisted in 2013 (68.0% prevalence). Vaccine (RotaTeq; Rotarix) strains were detected in 0.6%-3.4% of genotyped samples each season. Uncommon and unusual strains (eg, G8P, G3P, G2P, G3P, G3P, G24P, G4P, and G9P) were detected sporadically over the study period. Year, study site, and race were found to be significant predictors of genotype.Continued active surveillance is needed to monitor RVA genotypes in the United States and to detect potential changes since vaccine licensure.
View details for DOI 10.1093/infdis/jiw233
View details for PubMedID 27302190
View details for PubMedCentralID PMC5075963
Long-term Consistency in Rotavirus Vaccine Protection: RV5 and RV1 Vaccine Effectiveness in US Children, 2012-2013.
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
2015; 61 (12): 1792-9
Using a multicenter, active surveillance network from 2 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 vaccine effectiveness (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 2961 subjects, 402 rotavirus cases (14%) and 2559 rotavirus-negative AGE controls. RV1-specific VE analyses included 904 subjects, 100 rotavirus cases (11%), and 804 rotavirus-negative AGE controls. Over the 2 rotavirus seasons, the VE for a complete 3-dose vaccination with RV5 was 80% (confidence interval [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.
View details for DOI 10.1093/cid/civ872
View details for PubMedID 26449565
Rickettsia spp. 364D causing a cluster of eschar-associated illness, California.
The Pediatric infectious disease journal
2013; 32 (9): 1036-9
We describe the clinical course of the first 3 pediatric cases infected with Rickettsia spp. 364D. Although the pathogen was identified in California ticks decades ago, only recently have human cases been documented. Clinical features are generally mild, characterized by eschar, fever, headache, malaise and lymphadenopathy. Antigenic similarity among rickettsiae leads to cross-reactive antibody responses; definitive diagnosis requires molecular methods.
View details for DOI 10.1097/INF.0b013e318296b24b
View details for PubMedID 23594588
Effectiveness of pentavalent and monovalent rotavirus vaccines in concurrent use among US children <5 years of age, 2009-2011.
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
2013; 57 (1): 13-20
We assessed vaccine effectiveness (VE) for RotaTeq (RV5; 3 doses) and Rotarix (RV1; 2 doses) at reducing rotavirus acute gastroenteritis (AGE) inpatient and emergency department (ED) visits in US children.We enrolled children <5 years of age hospitalized or visiting the ED with AGE symptoms from November 2009-June 2010 and from November 2010-June 2011 at 7 medical institutions. Fecal specimens were tested for rotavirus by enzyme immunoassay and genotyped. Vaccination among laboratory-confirmed rotavirus cases was compared with rotavirus-negative AGE controls. Regression models calculated VE estimates for each vaccine, age, ethnicity, genotype, and clinical setting.RV5-specific analyses included 359 rotavirus cases and 1811 rotavirus-negative AGE controls. RV1-specific analyses included 60 rotavirus cases and 155 rotavirus-negative AGE controls. RV5 and RV1 were 84% (95% confidence interval [CI], 78%-88%) and 70% (95% CI, 39%-86%) effective, respectively, against rotavirus-associated ED visits and hospitalizations combined. By clinical setting, RV5 VE against ED and inpatient rotavirus-associated visits was 81% (95% CI, 70%-84%) and 86% (95% CI, 74%-91%), respectively. RV1 was 78% (95% CI, 46%-91%) effective against ED rotavirus disease; study power was insufficient to evaluate inpatient RV1 VE. No waning of immunity was evident during the first 4 years of life for RV5, nor during the first 2 years of life for RV1. RV5 provided genotype-specific protection against each of the predominant strains (G1P, G2P, G3P, G12P), while RV1 VE was statistically significant for the most common genotype, G3P.Both RV5 and RV1 significantly protected against medically attended rotavirus gastroenteritis in this real-world assessment.
View details for DOI 10.1093/cid/cit164
View details for PubMedID 23487388
View details for PubMedCentralID PMC4618548
Elite suppressor-derived HIV-1 envelope glycoproteins exhibit reduced entry efficiency and kinetics.
2009; 5 (4): e1000377
Elite suppressors (ES) are a rare subset of HIV-1-infected individuals who are able to maintain HIV-1 viral loads below the limit of detection by ultra-sensitive clinical assays in the absence of antiretroviral therapy. Mechanism(s) responsible for this elite control are poorly understood but likely involve both host and viral factors. This study assesses ES plasma-derived envelope glycoprotein (env) fitness as a function of entry efficiency as a possible contributor to viral suppression. Fitness of virus entry was first evaluated using a novel inducible cell line with controlled surface expression levels of CD4 (receptor) and CCR5 (co-receptor). In the context of physiologic CCR5 and CD4 surface densities, ES envs exhibited significantly decreased entry efficiency relative to chronically infected viremic progressors. ES envs also demonstrated slow entry kinetics indicating the presence of virus with reduced entry fitness. Overall, ES env clones were less efficient at mediating entry than chronic progressor envs. Interestingly, acute infection envs exhibited an intermediate phenotypic pattern not distinctly different from ES or chronic progressor envs. These results imply that lower env fitness may be established early and may directly contribute to viral suppression in ES individuals.
View details for DOI 10.1371/journal.ppat.1000377
View details for PubMedID 19360131
View details for PubMedCentralID PMC2661022
A quantitative affinity-profiling system that reveals distinct CD4/CCR5 usage patterns among human immunodeficiency virus type 1 and simian immunodeficiency virus strains.
Journal of virology
2009; 83 (21): 11016–26
The affinity of human immunodeficiency virus (HIV) envelope for CD4 and CCR5 appears to be associated with aspects of R5 virus (virus using the CCR5 coreceptor) pathogenicity. However, entry efficiency results from complex interactions between the viral envelope glycoprotein and both CD4 and CCR5, which limits attempts to correlate viral pathogenicity with surrogate measures of envelope CD4 and CCR5 affinities. Here, we present a system that provides a quantitative and comprehensive characterization of viral entry efficiency as a direct interdependent function of both CD4 and CCR5 levels. This receptor affinity profiling system also revealed heretofore unappreciated complexities underlying CD4/CCR5 usage. We first developed a dually inducible cell line in which CD4 and CCR5 could be simultaneously and independently regulated within a physiologic range of surface expression. Infection by multiple HIV type 1 (HIV-1) and simian immunodeficiency virus isolates could be examined simultaneously for up to 48 different combinations of CD4/CCR5 expression levels, resulting in a distinct usage pattern for each virus. Thus, each virus generated a unique three-dimensional surface plot in which viral infectivity varied as a function of both CD4 and CCR5 expression. From this functional form, we obtained a sensitivity vector along with corresponding metrics that quantified an isolate's overall efficiency of CD4/CCR5 usage. When applied to viral isolates with well-characterized sensitivities to entry/fusion inhibitors, the vector metrics were able to encapsulate their known biological phenotypes. The application of the vector metrics also indicated that envelopes derived from elite suppressors had overall-reduced entry efficiencies compared to those of envelopes derived from chronically infected viremic progressors. Our affinity-profiling system may help to refine studies of R5 virus tropism and pathogenesis.
View details for DOI 10.1128/JVI.01242-09
View details for PubMedID 19692480
View details for PubMedCentralID PMC2772777
Congenital brain tumors - Case series and review of the literature
JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY
2008; 30 (4): 326–31
Congenital brain tumors are rare and make up only 2% of all pediatric central nervous system tumors. We present 12 cases of congenital brain tumors of various histopathologies. Most of these tumors were of astrocytic lineage. One patient was diagnosed before birth with prenatal ultrasound, but the rest were diagnosed after birth owing to increased head circumference. Four patients received adjuvant chemotherapy after surgery. None received radiation therapy. Seven out of 12 (58%) are long-term survivors. Four of these survivors (57%) have significant neurocognitive or psychomotor impairment. Although rare, congenital brain tumors are one of the more common tumors presenting in the perinatal period and generally carry a poor prognosis. Novel therapies are needed to improve efficacy and decrease the devastating side effects of treatment in this age group.
View details for DOI 10.1097/MPH.0b013e3181647bf0
View details for Web of Science ID 000254880800014
View details for PubMedID 18391706