Gregory A Storch

Washington University in St. Louis, San Luis, Missouri, United States

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Publications (197)1108.76 Total impact

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    ABSTRACT: The potential to rapidly capture the entire microbial community structure or/and gene content makes metagenomic sequencing an attractive tool for pathogen identification and detection of resistance/virulence genes in clinical settings. Here, we assessed the consistency between PCR from a diagnostic laboratory, qPCR from a research laboratory, 16S rRNA gene sequencing and metagenomic shotgun sequencing (MSS) in Clostridium difficile identification in diarrhea stool samples. Twenty-two C. difficile positive diarrhea samples identified by PCR and qPCR and five C. difficile negative diarrhea controls were studied. C. difficile was detected in 90.9% of C. difficile positive samples using 16S rRNA gene sequencing, and 86.3% using MSS. Colony forming units (CFUs) inferred from qPCR analysis were positively correlated with the relative abundance of C. difficile from 16S rRNA gene sequencing (r2=-0.60) and MSS (r2=-0.55). C. difficile was co-detected with Clostridium perfringens, norovirus, sapovirus, parechovirus and anellovirus in 3.7%-27.3% of the samples. A high load of Candida spp was found in a symptomatic control sample in which no causative agents for diarrhea were identified in routine clinical testing. Beta-lactamase and tetracycline resistance genes were the most prevalent (25.9%) antibiotic resistance genes in these samples. In summary, the proof-of-concept study demonstrated that next generation sequencing (NGS) in pathogen detection is moderately correlated with laboratory testing and is advantageous in detecting pathogens without a priori knowledge.
    No preview · Article · Dec 2015 · Journal of Clinical Microbiology
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    ABSTRACT: Introduction: Respiratory viruses are increasingly recognized as significant etiologies of pneumonia among hospitalized patients. Advanced technologies using multiplex molecular assays and polymerase-chain reaction increase the ability to identify viral pathogens and may ultimately impact antibacterial use. Method: This was a single-center retrospective cohort study to evaluate the impact of antibacterials in viral pneumonia on clinical outcomes and subsequent multidrug-resistant organism (MDRO) infections/colonization. Patients admitted from March 2013 to November 2014 with positive respiratory viral panels (RVP) and radiographic findings of pneumonia were included. Patients transferred from an outside hospital or not still hospitalized 72 hours after the RVP report date were excluded. Patients were categorized based on exposure to systemic antibacterials: less than 3 days representing short-course therapy and 3 to 10 days being long-course therapy. Results: A total of 174 patients (long-course, n = 67; short-course, n = 28; mixed bacterial-viral infection, n = 79) were included with most being immunocompromised (56.3 %) with active malignancy the primary etiology (69.4 %). Rhinovirus/Enterovirus (23 %), Influenza (19 %), and Parainfluenza (15.5 %) were the viruses most commonly identified. A total of 13 different systemic antibacterials were used as empiric therapy in the 95 patients with pure viral infection for a total of 466 days-of-therapy. Vancomycin (50.7 %), cefepime (40.3 %), azithromycin (40.3 %), meropenem (23.9 %), and linezolid (20.9 %) were most frequently used. In-hospital mortality did not differ between patients with viral pneumonia in the short-course and long-course groups. Subsequent infection/colonization with a MDRO was more frequent in the long-course group compared to the short-course group (53.2 vs 21.1 %; P = 0.027). Conclusion: This study found that long-course antibacterial use in the setting of viral pneumonia had no impact on clinical outcomes but increased the incidence of subsequent MDRO infection/colonization.
    Preview · Article · Dec 2015 · Critical Care
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    Kristine M Wylie · George M Weinstock · Gregory A Storch
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    ABSTRACT: Background: We observed an increase in the number of rotavirus cases in the St. Louis area during the 2012-2013 rotavirus season compared with recent seasons. We aimed to determine whether the rotavirus cases during the 2012-2013 rotavirus season were of types not included in licensed vaccines. Methods: Microbiology laboratories of 3 children's hospitals in St. Louis provided samples that were positive using rapid antigen tests from 2010 to 2013. The majority of samples were from St. Louis Children's Hospital. We determined rotavirus genotypes by polymerase chain reaction tests and further characterized a subset of viruses by genome sequencing and comparative sequence analysis. Results: Eighty-six percent (24 of 28) of typed viruses analyzed from the 2012-2013 rotavirus season were G12. We performed whole genome sequencing on 8 G12 viruses, all of which were VP4 type P[8]. The sequenced viruses showed differences from vaccine strains in major antigenic epitopes on the VP7 protein, but most epitopes on VP4 were conserved. Rotavirus vaccine histories were available for 11 G12 cases, of whom 10 had not been vaccinated. Conclusions: G12 was a dominant community-wide genotype in 2013. Most of the G12 cases for whom vaccine histories were available had not received rotavirus vaccine. The experience demonstrates the potential for rapid shifts in rotavirus genotype distribution and underscores the need for vigilant surveillance to detect unusual genotypes that might escape from vaccine protection.
    Full-text · Article · Oct 2015
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    ABSTRACT: Specific viruses are associated with pediatric myocarditis, but the prevalence of viral DNAemia detected by blood polymerase chain reaction (PCR) is unknown. We evaluated the prevalence of known cardiotropic viruses (enterovirus, adenovirus, human herpesvirus 6, and parvovirus B19) in children with clinical myocarditis (n = 21). Results were compared to pediatric controls with similar viral PCR testing. The majority of positive PCR (89 %) was noted in children ≤12 months of age at diagnosis compared to older children. Infant myocarditis patients (8/10) had increased the prevalence of PCR positivity compared to infant pediatric controls (4/114) (p < 0.0001). Other than age, patient characteristics at diagnosis were similar between PCR-positive and PCR-negative patients. Both PCR-negative myocarditis infants had clinical recovery at follow-up. Of the PCR-positive myocarditis infants, 4 had clinical recovery, 2 developed chronic cardiomyopathy, 1 underwent heart transplant, and 1 died. Infants with clinical myocarditis have a high rate of blood viral positivity, which is higher compared to older children with myocarditis and healthy infant controls. Age-related differences in PCR positivity may be due to differences in host and/or virus characteristics. Our findings suggest that viral blood PCR may be a useful diagnostic tool and identify patients who would potentially benefit from virus-specific therapy.
    No preview · Article · Oct 2015 · Pediatric Cardiology
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    Todd N Wylie · Kristine M Wylie · Brandi N Herter · Gregory A Storch
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    ABSTRACT: Metagenomic shotgun sequencing (MSS) is an important tool for characterizing viral populations. It is culture-independent, requires no a priori knowledge of the viruses in the sample, and may provide useful genomic information. However, MSS can lack sensitivity and may yield insufficient data for detailed analysis. We have created a targeted sequence capture panel, ViroCap, designed to enrich nucleic acid from DNA and RNA viruses from 34 families that infect vertebrate hosts. A computational approach condensed nearly 1 billion base pair (bp) of viral reference sequence into less than 200 million bp of unique, representative sequence suitable for targeted sequence capture. We compared the effectiveness of detecting viruses in standard MSS versus MSS following targeted sequence capture. First, we analyzed two sets of samples, one derived from samples submitted to a diagnostic virology laboratory and one derived from samples collected in a study of fever in children. We detected 14 and 18 viruses in the two sets, comprising 19 genera from 10 families, with dramatic enhancement of genome representation following capture enrichment. The median fold-increases in percent viral reads post-capture were 674 and 296. Median breadth of coverage increased from 2.1% to 83.2% post-capture in the first set and from 2.0% to 75.6% in the second set. Next, we analyzed samples containing a set of diverse anellovirus sequences and demonstrated that ViroCap could be used to detect viral sequences with up to 58% variation from the references used to select capture probes. ViroCap substantially enhances MSS for a comprehensive set of viruses and has utility for research and clinical applications.
    Full-text · Article · Sep 2015 · Genome Research
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    Gregory A Storch

    Preview · Article · Aug 2015 · Clinical Infectious Diseases

  • No preview · Article · Jul 2015 · The Journal of allergy and clinical immunology
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    ABSTRACT: We have developed and evaluated a real-time reverse transcription PCR (RT-PCR) assay for detection of human enterovirus D68 (EV-D68) in clinical specimens. This assay was developed in response to the unprecedented 2014 nationwide EV-D68 outbreak associated with severe respiratory illness in the United States. As part of our evaluation of the outbreak, we sequenced and published the genome sequence of the EV-D68 virus circulating in St. Louis, Missouri. This sequence, along with other GenBank® sequences from past EV-D68 occurrences, was used to computationally select a region of EV-D68 appropriate for targeting in a strain-specific RT-PCR assay. The RT-PCR assay amplifies a segment of the VP-1 gene with an analytic limit of detection of 4 copies per reaction, and was more sensitive than commercially available assays that detect enteroviruses and rhinoviruses without distinguishing between the two, including three multiplex respiratory panels approved for clinical use by the FDA. The assay did not detect any other enteroviruses or rhinoviruses tested, and did detect divergent strains of EV-D68, including the first EV-D68 strain (Fermon) identified in California in 1962. This assay should be useful for identifying and studying current and future outbreaks of EV-D68 viruses. Copyright © 2015, American Society for Microbiology. All Rights Reserved.
    Full-text · Article · Jun 2015 · Journal of clinical microbiology

  • No preview · Article · Jun 2015 · Journal of Cystic Fibrosis
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    Full-text · Article · May 2015 · Emerging infectious diseases
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    Full-text · Article · Jan 2015 · Emerging infectious diseases

  • No preview · Article · Dec 2014 · Progress in Pediatric Cardiology
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    ABSTRACT: Background Infections with cytomegalovirus (CMV) and Epstein-Barr virus (EBV) remain important in solid organ transplantation. Quantitative viral nucleic acid testing is a major advance to patient management. These assays are limited by a lack of standardization, resulting in viral load measurements that differ among clinical laboratories. The variability in viral load measurements makes interpretation of multicenter clinical trials data difficult. This study compares the current practices in CMV and EBV viral load testing at four large transplant centers participating in multicenter Clinical Trials in Organ Transplantation and the Clinical Trials in Organ Transplantation in Children (CTOT and CTOTC).Methods Viral load testing was performed on well-defined viral preparations according to standard operating procedures at each site.ResultsAmong centers, CMV viral load testing was accurate compared to WHO International Standards and within acceptable variation for this testing method. Epstein-Barr virus viral load data were more variable and less accurate despite the use of international standards.Conclusions These data suggest that comparison of CMV, but not EBV, viral load measurements at these sites is possible using current assays and control standards. Standardization of these assays is facilitated using the WHO International Standards and will allow comparison of viral load results among transplant centers. Assay standardization must be performed prior to initiation of multicenter trials.
    Full-text · Article · Oct 2014 · Clinical Transplantation
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    ABSTRACT: Background The Human Microbiome Project (HMP) was undertaken with the goal of defining microbial communities in and on the bodies of healthy individuals using high-throughput, metagenomic sequencing analysis. The viruses present in these microbial communities, the `human virome¿, are an important aspect of the human microbiome that is particularly understudied in the absence of overt disease. We analyzed eukaryotic double-stranded DNA (dsDNA) viruses, together with dsDNA replicative intermediates of single-stranded DNA viruses, in metagenomic sequence data generated by the HMP. 706 samples from 102 subjects were studied, with each subject sampled at up to five major body habitats: nose, skin, mouth, vagina, and stool. Fifty-one individuals had samples taken at two or three time points 30 to 359 days apart from at least one of the body habitats.ResultsWe detected an average of 5.5 viral genera in each individual. At least 1 virus was detected in 92% of the individuals sampled. These viruses included herpesviruses, papillomaviruses, polyomaviruses, adenoviruses, anelloviruses, parvoviruses, and circoviruses. Each individual had a distinct viral profile, demonstrating the high interpersonal diversity of the virome. Some components of the virome were stable over time.Conclusions This study is the first to use high-throughput DNA sequencing to describe the diversity of eukaryotic dsDNA viruses in a large cohort of normal individuals who were sampled at multiple body sites. Our results show that the human virome is a complex component of the microbial flora. Some viruses establish long-term infections that may be associated with increased risk or possibly with protection from disease. A better understanding of the composition and dynamics of the virome may hold important keys to human health.
    Full-text · Article · Sep 2014 · BMC Biology
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    ABSTRACT: Background Human Herpes Virus type-6 (HHV-6) is a significant cause of the febrile illness roseola infantum in young children. Infection with HHV-6 typically causes a self-limited febrile illness, but occasionally is associated with central nervous system manifestations, including febrile seizures and encephalitis. Host factors associated with severe manifestations of HHV-6-associated neurologic disease remain poorly characterized. Case Reports We report two cases of previously healthy young boys with HHV-6-associated encephalitis who developed a progressive, and ultimately fatal, encephalopathy with refractory movement disorder concurrent with acquisition of acute HHV-6 infection. Both children were treated with the antiviral ganciclovir without improvement in their neurologic symptoms, although quantitative HHV-6 PCR of CSF and/or blood confirmed a decline in viral load with treatment. The clinical course in both cases was most consistent with Alpers-Huttenlocher syndrome, given the intractable seizures, developmental regression and, ultimately, death due to liver and renal failure. In support of this, post-mortem analysis identified both children to be compound heterozygotes for mutations in the mitochondrial polymerase γ gene, POLG. Conclusions POLG mutations are associated with Alpers-Huttenlocher syndrome, however no prior studies have examined the role of acute HHV-6 infection in these patients presenting with severe neurologic disease. It is possible the POLG mutation phenotype was unmasked and/or exacerbated by HHV-6 infection in these two patients, potentially contributing to a more rapid clinical deterioration. This report provides new insight into a previously unrecognized association between POLG mutations and poor neurologic outcome following HHV-6 infection.
    No preview · Article · Sep 2014 · Pediatric Neurology
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    ABSTRACT: The aim of this study was to identify the best practices for the detection of Shiga toxin-producing Escherichia coli (STEC) in children with diarrheal illness treated at a tertiary care center, i.e., sorbitol-MacConkey (SMAC) agar culture, enzyme immunoassay (EIA) for Shiga toxin, or the simultaneous use of both methods. STEC was detected in 100 of 14,997 stool specimens submitted for enteric culture (0.7%), with 65 cases of E. coli O157. Among E. coli O157 isolates, 57 (88%) were identified by both SMAC agar culture and EIA, 6 (9%) by SMAC agar culture alone, and 2 (3%) by EIA alone. Of the 62 individuals with diarrheal hemolytic uremic syndrome (HUS) seen at our institution during the study period, 16 (26%) had STEC isolated from cultures at our institution and 15 (24%) had STEC isolated at other institutions. No STEC was recovered in 31 cases (50%). Of the HUS cases in which STEC was isolated, 28 (90%) were attributable to E. coli O157 and 3 (10%) were attributable to non-O157 STEC. Consistent with previous studies, we have determined that a subset of E. coli O157 infections will not be detected if an agar-based method is excluded from the enteric culture workup; this has both clinical and public health implications. The best practice would be concomitant use of an agar-based method and a Shiga toxin EIA, but a Shiga toxin EIA should not be considered to be an adequate stand-alone test for detection of E. coli O157 in clinical samples.
    Preview · Article · Jul 2014 · Journal of Clinical Microbiology
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    ABSTRACT: A current controversy is whether patients with sepsis progress to an immunosuppressed state. We hypothesized that reactivation of latent viruses occurred with prolonged sepsis thereby providing evidence of clinically-relevant immunosuppression and potentially providing a means to serially-monitor patients' immune status. Secondly, if viral loads are markedly elevated, they may contribute to morbidity and mortality. This study determined if reactivation of herpesviruses, polyomaviruses, and the anellovirus TTV occurred in sepsis and correlated with severity. Serial whole blood and plasma samples from 560 critically-ill septic, 161 critically-ill non-septic, and 164 healthy age-matched patients were analyzed by quantitative-polymerase-chain-reaction for cytomegalovirus (CMV), Epstein-Barr (EBV), herpes-simplex (HSV), human herpes virus-6 (HHV-6), and TTV. Polyomaviruses BK and JC were quantitated in urine. Detectable virus was analyzed with respect to secondary fungal and opportunistic bacterial infections, ICU duration, severity of illness, and survival. Patients with protracted sepsis had markedly increased frequency of detectable virus. Cumulative viral DNA detection rates in blood were: CMV (24.2%), EBV (53.2%), HSV (14.1%), HHV-6 (10.4%), and TTV (77.5%). 42.7% of septic patients had presence of two or more viruses. The 50% detection rate for herpesviruses was 5-8 days after sepsis onset. A small subgroup of septic patients had markedly elevated viral loads (>104-106 DNA copies/ml blood) for CMV, EBV, and HSV. Excluding TTV, DNAemia was uncommon in critically-ill non-septic patients and in age-matched healthy controls. Compared to septic patients without DNAemia, septic patients with viremia had increased fungal and opportunistic bacterial infections. Patients with detectable CMV in plasma had higher 90-day mortality compared to CMV-negative patients; p<0.05. Reactivation of latent viruses is common with prolonged sepsis, with frequencies similar to those occurring in transplant patients on immunosuppressive therapy and consistent with development of an immunosuppressive state. Whether reactivated latent viruses contribute to morbidity and mortality in sepsis remains unknown.
    Full-text · Article · Jun 2014 · PLoS ONE
  • Jina Lee · Gregory A Storch
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    ABSTRACT: Multiplex molecular assays now make it possible for clinical laboratories to detect human coronaviruses (HCoV). We investigated the clinical characteristics of HCoV-OC43 and HCoV-NL63 in patients <5 years of age during a recent coronavirus season. Respiratory viruses were detected using a multiplex molecular assay at St. Louis Children`s Hospital starting in November 2012. We analyzed demographic and clinical data from all patients <5 years old with solo detection of HCoV-OC43 (n=52) and HCoV-NL63 (n=44) and for comparison, samples of children with respiratory syncytial virus (RSV), parainfluenza virus (PIV), and picornaviruses. During the study period, HCoV-OC43 (4%) was the 5 and HCoV-NL63 the 8 (2%) most common respiratory virus. Coinfections were detected in 35% and 38% of children with HCoV-OC43 and HCoV-NL63, respectively. Croup was more common with HCoV-NL63 (30%) than with HCoV-OC43 (2%). Lower respiratory tract infection occurred in 33% of children with HCoV-OC43 and 25% of children with HCoV-NL63. Severe illness was less common in HCoV-NL63, HCoV-OC43, and PIV (14%, each) compared with RSV (30%) and picornaviruses (26%) (p=0.055 for HCoVs combined compared with the other respiratory viruses), and occurred mainly in those with underlying medical conditions. Infections caused by HCoV-OC43 and HCoV-NL63 are common and include some with lower respiratory tract involvement and severe disease, especially in children with underlying medical conditions. Overall, a substantial burden of disease associated with both HCoV-OC43 and HCoV-NL63 was observed for hospitalized children younger than 5 years old.
    No preview · Article · Feb 2014 · The Pediatric Infectious Disease Journal
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    ABSTRACT: The prevalence and seasonal distribution of norovirus infection in children is not well defined. In this study, stool specimens from children suspected of having gastroenteritis were evaluated for the presence of norovirus. When tested retrospectively, 17.4% of samples were positive, primarily with Genogroup GII, peaking in fall and winter.
    No preview · Article · Jan 2014
  • Vikas R Dharnidharka · Gregory A Storch · Daniel C Brennan

    No preview · Article · Nov 2013 · New England Journal of Medicine

Publication Stats

7k Citations
1,108.76 Total Impact Points

Institutions

  • 1987-2015
    • Washington University in St. Louis
      • • Department of Pediatrics
      • • Department of Medicine
      San Luis, Missouri, United States
  • 2011
    • Washington & Lee University
      Лексингтон, Virginia, United States
  • 1999-2010
    • St. Luke's Hospital (MO, USA)
      Сент-Луис, Michigan, United States
    • The Ohio State University
      • Department of Veterinary Biosciences
      Columbus, Ohio, United States
  • 2008
    • Johns Hopkins University
      • Department of Pediatrics
      Baltimore, Maryland, United States
  • 2007
    • Mercy Hospital St. Louis
      San Luis, Missouri, United States
  • 2005
    • University of Missouri - Kansas City
      • Division of Pharmacy Practice
      Kansas City, MO, United States
  • 2000
    • University of Missouri
      • Veterinary Medical Diagnostic Laboratory
      Columbia, Missouri, United States
  • 1995
    • Barnes Jewish Hospital
      San Luis, Missouri, United States
  • 1994
    • Valley Children's Hospital
      Мадера, California, United States