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Joshua M Colvin,
Jared T Muenzer,
David M Jaffe,
Avraham Smason,
Elena Deych,
William D Shannon,
Max Q Arens,
Richard S Buller,
Wai-Ming Lee,
Erica J Sodergren Weinstock,
George M Weinstock, Gregory A Storch
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Joshua M Colvin,
Jared T Muenzer,
David M Jaffe,
Avraham Smason,
Elena Deych,
William D Shannon,
Max Q Arens,
Richard S Buller,
Wai-Ming Lee,
Erica J Sodergren Weinstock,
George M Weinstock, Gregory A Storch
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ABSTRACT: OBJECTIVE:Fever without an apparent source is common in young children. Currently in the United States, serious bacterial infection is unusual. Our objective was to determine specific viruses that might be responsible.METHODS:We enrolled children aged 2 to 36 months with temperature of 38°C or greater without an apparent source or with definite or probable bacterial infection being evaluated in the St Louis Children's Hospital Emergency Department and afebrile children having ambulatory surgery. Blood and nasopharyngeal swab samples were tested with an extensive battery of virus-specific polymerase chain reaction assays.RESULTS:One or more viruses were detected in 76% of 75 children with fever without an apparent source, 40% of 15 children with fever and a definite or probable bacterial infection, and 35% of 116 afebrile children (P < .001). Four viruses (adenovirus, human herpesvirus 6, enterovirus, and parechovirus) were predominant, being detected in 57% of children with fever without a source, 13% of children with fever and definite or probable bacterial infection, and 7% of afebrile children (P < .001). Thirty-four percent of 146 viral infections were detected only by polymerase chain reaction performed on blood. Fifty-one percent of children with viral infections and no evidence of bacterial infection were treated with antibiotics.CONCLUSIONS:Viral infections are frequent in children with fever without an apparent source. Testing of blood in addition to nasopharyngeal secretions expanded the range of viruses detected. Future studies should explore the utility of testing for the implicated viruses. Better recognition of viruses that cause undifferentiated fever in young children may help limit unnecessary antibiotic use.
PEDIATRICS 11/2012; · 4.47 Impact Factor
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ABSTRACT: The human virome is the collection of all viruses that are found in or on humans, including both eukaryotic and prokaryotic viruses. Eukaryotic viruses clearly have important effects on human health, ranging from mild, self-limited acute or chronic infections to those with serious or fatal consequences. Prokaryotic viruses can also influence human health by affecting bacterial community structure and function. Therefore, definition of the virome is an important step toward understanding how microbes affect human health and disease. We review progress in virome analysis, which has been driven by advances in high-throughput, deep sequencing technology. Highlights from these studies include the association of viruses with clinical phenotypes and description of novel viruses that may be important pathogens. Together these studies indicate that analysis of the human virome is critical as we aim to understand how microbial communities influence human health and disease. Descriptions of the human virome will stimulate future work to understand how the virome affects long-term human health, immunity, and response to coinfections. Analysis of the virome ultimately may affect the treatment of patients with a variety of clinical syndromes.
Translational research : the journal of laboratory and clinical medicine. 04/2012; 160(4):283-90.
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ABSTRACT: Unexplained fever (UF) is a common problem in children under 3 years old. Although virus infection is suspected to be the cause of most of these fevers, a comprehensive analysis of viruses in samples from children with fever and healthy controls is important for establishing a relationship between viruses and UF. We used unbiased, deep sequencing to analyze 176 nasopharyngeal swabs (NP) and plasma samples from children with UF and afebrile controls, generating an average of 4.6 million sequences per sample. An analysis pipeline was developed to detect viral sequences, which resulted in the identification of sequences from 25 viral genera. These genera included expected pathogens, such as adenoviruses, enteroviruses, and roseoloviruses, plus viruses with unknown pathogenicity. Viruses that were unexpected in NP and plasma samples, such as the astrovirus MLB-2, were also detected. Sequencing allowed identification of virus subtype for some viruses, including roseoloviruses. Highly sensitive PCR assays detected low levels of viruses that were not detected in approximately 5 million sequences, but greater sequencing depth improved sensitivity. On average NP and plasma samples from febrile children contained 1.5- to 5-fold more viral sequences, respectively, than samples from afebrile children. Samples from febrile children contained a broader range of viral genera and contained multiple viral genera more frequently than samples from children without fever. Differences between febrile and afebrile groups were most striking in the plasma samples, where detection of viral sequence may be associated with a disseminated infection. These data indicate that virus infection is associated with UF. Further studies are important in order to establish the range of viral pathogens associated with fever and to understand of the role of viral infection in fever. Ultimately these studies may improve the medical treatment of children with UF by helping avoid antibiotic therapy for children with viral infections.
PLoS ONE 01/2012; 7(6):e27735. · 4.09 Impact Factor
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ABSTRACT: Changes in the BK virus archetypal noncoding control region (NCCR) have been associated with BK-virus-associated nephropathy (BKVAN). Whether sustained viremia, a surrogate for BKVAN, is associated with significant changes in the BK-NCCR is unknown. We performed PCR amplification and sequencing of (1) stored urine and (2) plasma samples from the time of peak viremia from 11 patients with sustained viremia who participated in a 200-patient clinical trial. The antimetabolite was withdrawn for BK viremia and reduction of the calcineurin inhibitor for sustained BK viremia. DNA sequencing from the 11 patients with sustained viremia revealed 8 insertions, 16 transversions, 3 deletions, and 17 transitions. None were deemed significant. No patient developed clinically evident BKVAN. Our data support, at a genomic level, the effectiveness of reduction of immunosuppression for prevention of progression from viremia to BKVAN.
Journal of Transplantation 01/2012; 2012:761283.
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ABSTRACT: The Anelloviridae family consists of non-enveloped, circular, single-stranded DNA viruses. Three genera of anellovirus are known to infect humans, named TTV, TTMDV, and TTMV. Although anelloviruses were initially thought to cause non-A-G viral hepatitis, continued research has shown no definitive associations between anellovirus and human disease to date. Using high-throughput sequencing, we investigated the association between anelloviruses and fever in pediatric patients 2-36 months of age. We determined that although anelloviruses were present in a large number of specimens from both febrile and afebrile patients, they were more prevalent in the plasma and nasopharyngeal (NP) specimens of febrile patients compared to afebrile controls. Using PCR to detect each of the three species of anellovirus that infect humans, we found that anellovirus species TTV and TTMDV were more prevalent in the plasma and NP specimens of febrile patients compared to afebrile controls. This was not the case for species TTMV which was found in similar percentages of febrile and afebrile patient specimens. Analysis of patient age showed that the percentage of plasma and NP specimens containing anellovirus increased with age until patients were 19-24 months of age, after which the percentage of anellovirus positive patient specimens dropped. This trend was striking for TTV and TTMDV and very modest for TTMV in both plasma and NP specimens. Finally, as the temperature of febrile patients increased, so too did the frequency of TTV and TTMDV detection. Again, TTMV was equally present in both febrile and afebrile patient specimens. Taken together these data indicate that the human anellovirus species TTV and TTMDV are associated with fever in children, while the highly related human anellovirus TTMV has no association with fever.
PLoS ONE 01/2012; 7(11):e50937. · 4.09 Impact Factor
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ABSTRACT: Macrolide-resistant Mycoplasma pneumoniae is widespread in Asia, and severe cases of pneumonia have been described in children. Little information is available about the resistance pattern in the United States. We collected respiratory samples from 49 patients with Mycoplasma infection in the central United States between 2007 and 2010. We found a macrolide resistance rate of 8.2%. Resistance should be considered when patients with M. pneumoniae infection do not have a satisfactory response to macrolides. Alternative antibiotics include tetracyclines or fluoroquinolones.
The Pediatric Infectious Disease Journal 12/2011; 31(4):409-0. · 3.58 Impact Factor
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ABSTRACT: Astroviruses cause diarrhea, but it is not known whether they circulate in human plasma. Astrovirus MLB2 was recently discovered in diarrhea samples from children. We detected MLB2 in the plasma of a febrile child, which suggests that MLB2 has broader tropism than expected and disease potential beyond the gastrointestinal tract.
Emerging Infectious Diseases 11/2011; 17(11):2050-2. · 6.79 Impact Factor
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ABSTRACT: The widespread use of the Haemophilus influenzae serotype b conjugate vaccine in developed countries has led to a dramatic reduction in invasive disease because of that serotype. The H. influenzae serotype b vaccine provides no significant protection against nontypeable or non-b encapsulated strains. Invasive disease due to H. influenzae serotype f (Hif) remains uncommon in children, although a higher incidence is reported in those with chronic disease and/or immunodeficiency. We report the case of a 5-year-old female patient with human immunodeficiency virus infection who developed a large thigh abscess and cellulitis because of Hif. The case illustrates an unusual presentation of invasive Hif infection and reiterates the need to consider uncommon pathogens as etiological agents in disease presenting in immunocompromised hosts.
Infectious Disease in Clinical Practice 10/2011; 19(6):e21-e23.
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ABSTRACT: Despite a paucity of evidence, decolonization measures are prescribed for outpatients with recurrent Staphylococcus aureus skin and soft-tissue infection (SSTI).
Compare the effectiveness of 4 regimens for eradicating S. aureus carriage.
Open-label, randomized controlled trial. Colonization status and recurrent SSTI were ascertained at 1 and 4 months.
Barnes-Jewish and St. Louis Children's Hospitals, St. Louis, Missouri, 2007-2009.
Three hundred patients with community-onset SSTI and S. aureus colonization in the nares, axilla, or inguinal folds.
Participants were randomized to receive no therapeutic intervention (control subjects) or one of three 5-day regimens: 2% mupirocin ointment applied to the nares twice daily, intranasal mupirocin plus daily 4% chlorhexidine body washes, or intranasal mupirocin plus daily dilute bleach water baths.
Among 244 participants with 1-month colonization data, modified intention-to-treat analysis revealed S. aureus eradication in 38% of participants in the education only (control) group, 56% of those in the mupirocin group (P = .03 vs controls), 55% of those in the mupirocin and chlorhexidine group (P = .05), and 63% off those in the mupirocin and bleach group (P = .006). Of 229 participants with 4-month colonization data, eradication rates were 48% in the control group, 56% in the mupirocin only group (P = .40 vs controls), 54% in the mupirocin and chlorhexidine group (P = .51), and 71% in the mupirocin and bleach group (P = .02). At 1 and 4 months, recurrent SSTIs were reported by 20% and 36% of participants, respectively.
An inexpensive regimen of dilute bleach baths, intranasal mupirocin, and hygiene education effectively eradicated S. aureus over a 4-month period. High rates of recurrent SSTI suggest that factors other than endogenous colonization are important determinants of infection. Trial registration. ClinicalTrials.gov identifier: NCT00513799.
Infection Control and Hospital Epidemiology 09/2011; 32(9):872-80. · 3.67 Impact Factor
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Journal of clinical microbiology 07/2011; 49(7):2784. · 4.16 Impact Factor
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Journal of clinical microbiology 07/2011; 49(7):2389, 2784. · 4.16 Impact Factor
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ABSTRACT: BK and JC polyomaviruses can reactivate after transplantation, causing renal dysfunction and graft loss. The incidence of JC reactivation after renal transplant is not well understood. Here, we characterized JC reactivation using samples collected during the first year after transplantation from 200 kidney recipients. We detected BK and JC viruses in the urine of 35 and 16% of transplant recipients, respectively. The median viral load in the urine was 400 times higher for BK virus than JC virus. The presence of BK viruria made concurrent JC viruria less likely: JC viruria was detected in 22% of non-BK viruric recipients compared with 4% of BK viruric recipients (P=0.001). The co-detection rate was 1.5%, which is less than the expected 5.6% if reactivation of each virus was independent (P=0.001). We did not observe JC viremia, JC nephropathy, or progressive multifocal leukoencephalopathy. The onset of JC viruria was associated with donor, but not recipient, JC-specific antibody in a titer-dependent fashion and inversely associated with donor and recipient BK-specific antibody. Donor and recipient JC seropositivity did not predict BK viruria or viremia. In conclusion, among renal transplant recipients, infection with one polyomavirus inversely associates with infection with the other.
Journal of the American Society of Nephrology 05/2011; 22(5):825-31. · 9.66 Impact Factor
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ABSTRACT: The natural history of contemporary Staphylococcus aureus nasal colonization was evaluated in community children during a 1-year period. Methicillin-susceptible S. aureus nasal carriage was more persistent than methicillin-resistant S. aureus nasal carriage, which was usually self-limited. Children with persistent staphylococcal colonization often carried identical strains. Identification of persistent methicillin-resistant S. aureus carriers might inform strategies for decolonization and reduction of staphylococcal transmission.
The Pediatric Infectious Disease Journal 04/2011; 30(4):349-51. · 3.58 Impact Factor
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ABSTRACT: Despite the ubiquity of invasive organisms and their often deleterious effects on native flora and fauna, the consequences of biological invasions for human health and the ecological mechanisms through which they occur are rarely considered. Here we demonstrate that a widespread invasive shrub in North America, Amur honeysuckle (Lonicera maackii), increases human risk of exposure to ehrlichiosis, an emerging infectious disease caused by bacterial pathogens transmitted by the lone star tick (Amblyomma americanum). Using large-scale observational surveys in natural areas across the St. Louis, Missouri region, we found that white-tailed deer (Odocoileus virginianus), a preeminent tick host and pathogen reservoir, more frequently used areas invaded by honeysuckle. This habitat preference translated into considerably greater numbers of ticks infected with pathogens in honeysuckle-invaded areas relative to adjacent honeysuckle-uninvaded areas. We confirmed this biotic mechanism using an experimental removal of honeysuckle, which caused a decrease in deer activity and infected tick numbers, as well as a proportional shift in the blood meals of ticks away from deer. We conclude that disease risk is likely to be reduced when honeysuckle is eradicated, and suggest that management of biological invasions may help ameliorate the burden of vector-borne diseases on human health.
Proceedings of the National Academy of Sciences 10/2010; 107(43):18523-7. · 9.68 Impact Factor
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ABSTRACT: Both prophylactic and preemptive oral valganciclovir therapy are effective for the management of cytomegalovirus (CMV) postrenal transplantation in the short term. The long-term effect of either strategy is less well defined.
We analyzed the data on 115 adult recipients previously enrolled in a prospective randomized controlled trial of prophylaxis versus preemptive therapy for CMV. The primary outcome was a composite of freedom from acute rejection, graft loss, or death. Secondary outcomes included individual primary outcomes, posttransplant cardiovascular events, new-onset diabetes mellitus after transplantation, achievement of goal blood pressure, change in body mass index, interstitial fibrosis/tubular atrophy, and change in renal function. The analysis period was a minimum of 48-month posttransplant or a date of death or graft loss, whichever was earlier.
The primary outcome was similar between groups (83% prophylactic vs. 81% preemptive, P=0.754). The secondary outcomes showed similarities between the prophylactic and preemptive groups. Four patients in the prophylactic group (8%) compared with none in the preemptive group (0%) died with a functioning graft, P=0.043.
Within the limitations of sample size, our data suggest that either strategy for the management of CMV immediately after transplantation seems effective for patient and graft survival in the long term. CMV management is one of the many therapeutic strategies incorporated into a renal transplantation protocol, which often differs among institutions, and the decision as to which approach to use remains center- and resource-specific. The increased incidence of death in the prophylactic group requires further investigation.
Transplantation 08/2010; 90(4):412-8. · 4.00 Impact Factor
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Kaharu C Sumino,
Michael J Walter,
Cassandra L Mikols,
Samantha A Thompson,
Monique Gaudreault-Keener,
Max Q Arens,
Eugene Agapov,
David Hormozdi,
Anne M Gaynor,
Michael J Holtzman, Gregory A Storch
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ABSTRACT: A specific diagnosis of a lower respiratory viral infection is often difficult despite frequent clinical suspicion. This low diagnostic yield may be improved by use of sensitive detection methods and biomarkers.
The prevalence, clinical predictors and inflammatory mediator profile of respiratory viral infection in serious acute respiratory illness were investigated. Sequential bronchoalveolar lavage (BAL) fluids from all patients hospitalised with acute respiratory illness over 12 months (n=283) were tested for the presence of 17 respiratory viruses by multiplex PCR assay and for newly discovered respiratory viruses (bocavirus, WU and KI polyomaviruses) by single-target PCR. BAL samples also underwent conventional testing (direct immunoflorescence and viral culture) for respiratory virus at the clinician's discretion. 27 inflammatory mediators were measured in a subset of the patients (n=64) using a multiplex immunoassay.
39 respiratory viruses were detected in 37 (13.1% of total) patients by molecular testing, including rhinovirus (n=13), influenza virus (n=8), respiratory syncytial virus (n=6), human metapneumovirus (n=3), coronavirus NL63 (n=2), parainfluenza virus (n=2), adenovirus (n=1) and newly discovered viruses (n=4). Molecular methods were 3.8-fold more sensitive than conventional methods. Clinical characteristics alone were insufficient to separate patients with and without respiratory virus. The presence of respiratory virus was associated with increased levels of interferon gamma-inducible protein 10 (IP-10) (p<0.001) and eotaxin-1 (p=0.017) in BAL.
Respiratory viruses can be found in patients with serious acute respiratory illness by use of PCR assays more frequently than previously appreciated. IP-10 may be a useful biomarker for respiratory viral infection.
Thorax 07/2010; 65(7):639-44. · 6.84 Impact Factor
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ABSTRACT: High-throughput multiplex assays for respiratory viruses are an important step forward in diagnostic virology. We compared one such assay, the PLx Multi-Code Respiratory Virus Panel (PLx-RVP), manufactured by Eragen Biosciences, Inc. (Madison, WI), with conventional virologic testing, consisting of fluorescent-antibody staining plus testing with the R-mix system and fibroblast tube cultures. The test set consisted of 410 archived respiratory specimens, mostly nasopharyngeal swabs, including 210 that had been positive by conventional testing for a balanced selection of common respiratory viruses. Specimens yielding discrepant results were evaluated using a panel of respiratory virus PCR assays developed, characterized, and validated with clinical specimens. PLx-RVP increased the total rate of detection of viruses by 35.8%, and there was a 25.7% increase in the rate of detection of positive specimens. Reference PCR assay results corroborated the PLx-RVP result for 54 (82%) of 66 discrepancies with conventional testing. Of the 12 specimens with discrepancies between PLx-RVp and the reference PCRs, 6 were positive for rhinovirus by PLx-RVP and the presence of rhinovirus was confirmed by nucleotide sequencing. The remaining six specimens included five in which the PLx-RVP failed to detect parainfluenza virus and one in which the detection of influenza A virus by PLx-RVP could not be confirmed by the reference PCR. Taking the results of the reference PCR assay results into account, the sensitivities of the PLx-RVP for individual viruses ranged from 94 to 100% and the specificities ranged from 99 to 100%. We conclude that PLx-RVP is a highly accurate system for the detection of respiratory viruses and significantly improves the rate of detection of these viruses compared to that by conventional virologic testing.
Journal of clinical microbiology 07/2010; 48(7):2387-95. · 4.16 Impact Factor
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ABSTRACT: Efforts to identify wildlife reservoirs for tick-borne pathogens are frequently limited by poor understanding of tick-host interactions and potentially transient infectivity of hosts under natural conditions. To identify reservoir hosts for lone star tick (Amblyomma americanum)-associated pathogens, we used a novel technology. In field-collected ticks, we used PCR to amplify a portion of the 18S rRNA gene in remnant blood meal DNA. Reverse line blot hybridization with host-specific probes was then used to subsequently detect and identify amplified DNA. Although several other taxa of wildlife hosts contribute to tick infection rates, our results confirm that the white-tailed deer (Odocoileus virginianus) is a reservoir host for several A. americanum-associated pathogens. Identification of host blood meal frequency and reservoir competence can help in determining human infection rates caused by these pathogens.
Emerging Infectious Diseases 03/2010; 16(3):433-40. · 6.79 Impact Factor
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Rachel C Orscheln,
David A Hunstad,
Stephanie A Fritz,
Jennifer A Loughman,
Kimberly Mitchell,
Emily K Storch,
Monique Gaudreault,
Patricia L Sellenriek,
Jon R Armstrong,
Elaine R Mardis, Gregory A Storch
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ABSTRACT: Within the current worldwide epidemic of community-acquired Staphylococcus aureus infections, attention has focused on the role of methicillin-resistant strains. We characterize methicillin-susceptible strains that also contribute to this epidemic.
We tracked cultures from abscess specimens submitted to the microbiology laboratory at St. Louis Children's Hospital and examined Panton-Valentine leukocidin (PVL) genes in methicillin-susceptible S. aureus (MSSA) isolates. We further characterized some isolates by multilocus sequence typing, pulsed-field gel electrophoresis, antibiotic susceptibility, accessory gene regulator (agr) allele, and presence of the arcA gene of the arginine catabolic mobile element.
From 1999 to 2007, we detected a 250-fold increase in cultures of abscesses yielding methicillin-resistant S. aureus (MRSA) and a 5-fold increase in abscess cultures yielding MSSA. MSSA isolates from abscesses and wounds were more likely to encode PVL than isolates from other sources. In contrast to PVL-negative isolates of MSSA, which were genetically diverse, PVL-positive isolates were predominantly multilocus sequence typing type 8 and agr type 1. More than half of PVL-positive MSSA isolates were resistant to erythromycin and susceptible to clindamycin with the absence of inducible resistance, a pattern uncommon in PVL-negative MSSA but frequent in the USA300 clone of MRSA. In addition, pulsed-field gel electrophoresis of PVL-positive MSSA strains revealed the USA300 pattern.
In addition to methicillin-resistant strains, the current epidemic of S. aureus infections includes infections caused by methicillin-susceptible strains that are closely related genetically and share phenotypic characteristics other than susceptibility to methicillin. These findings suggest that factors other than methicillin resistance are driving the epidemic.
Clinical Infectious Diseases 09/2009; 49(4):536-42. · 9.15 Impact Factor
