Richard L Hodinka

The Children's Hospital of Philadelphia, Filadelfia, Pennsylvania, United States

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Publications (94)375.88 Total impact

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    ABSTRACT: Two meetings, one sponsored by the Wellcome Trust in 2012 and the other by the Global Virology Foundation in 2013, assembled academic, public health and pharmaceutical industry experts to assess the challenges and opportunities for developing antivirals for the treatment of respiratory syncytial virus (RSV) infections. The practicalities of clinical trials and establishing reliable outcome measures in different target groups were discussed in the context of the regulatory pathways that could accelerate the translation of promising compounds into licensed agents. RSV drug development is hampered by the perceptions of a relatively small and fragmented market that may discourage major pharmaceutical company investment. Conversely, the public health need is far too large for RSV to be designated an orphan or neglected disease. Recent advances in understanding RSV epidemiology, improved point-of-care diagnostics, and identification of candidate antiviral drugs argue that the major obstacles to drug development can and will be overcome. Further progress will depend on studies of disease pathogenesis and knowledge provided from controlled clinical trials of these new therapeutic agents. The use of combinations of inhibitors that have different mechanisms of action may be necessary to increase antiviral potency and reduce the risk of resistance emergence. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.
    The Journal of Infectious Diseases 03/2015; 211 Suppl 1(Suppl 1):S1-S20. DOI:10.1093/infdis/jiu828 · 5.78 Impact Factor
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    ABSTRACT: Influenza viruses typically cause the most severe disease in children and elderly individuals. However, H1N1 viruses disproportionately affected middle-aged adults during the 2013-2014 influenza season. Although H1N1 viruses recently acquired several mutations in the hemagglutinin (HA) glycoprotein, classic serological tests used by surveillance laboratories indicate that these mutations do not change antigenic properties of the virus. Here, we show that one of these mutations is located in a region of HA targeted by antibodies elicited in many middle-aged adults. We find that over 42% of individuals born between 1965 and 1979 possess antibodies that recognize this region of HA. Our findings offer a possible antigenic explanation of why middle-aged adults were highly susceptible to H1N1 viruses during the 2013-2014 influenza season. Our data further suggest that a drifted H1N1 strain should be included in future influenza vaccines to potentially reduce morbidity and mortality in this age group.
    Proceedings of the National Academy of Sciences 10/2014; 111(44). DOI:10.1073/pnas.1409171111 · 9.81 Impact Factor
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    ABSTRACT: Background: Allogeneic hematopoietic stem cell transplantation (SCT) is often used as definitive therapy for hemophagocytic lymphohistiocytosis (HLH). Data on infectious complications in post-SCT HLH patients are limited, with no analyses comparing their infectious risk to other SCT recipients. This study compares post-SCT infection frequency and mortality rates between pediatric HLH and leukemia patients. Methods: All HLH SCT patients from 1997 to 2009 were identified from the bone marrow registry at The Children's Hospital of Philadelphia. HLH patients were matched one-to-one to leukemia SCT patients by age and transplant year. Data on demographics, donor source, conditioning regimens, microbiologically-proven infections, and vital status 6 months post-SCT were collected. Multivariate conditional Poisson and logistic/Cox regression models compared infection rate per follow-up days and mortality, respectively. Results: Eighteen HLH SCT patients (100%) had at least one infection, (median: 2; IQR: 1 to 4). Half of the leukemia SCT recipients had at least 1 infection (median: 1; IQR: 0 to 2). Compared to leukemia patients, HLH patients had a greater incidence of total infections (IRR: 2.47, 95% CI: 1.01 to 6.05; Table 1). After adjusting for sex, conditioning regimen, and antithymocyte or antilymphocyte globulin (ATG/ALG) use, this difference was no longer significant (IRR: 1.69, 95% CI: 0.72 to 3.95). Receipt of ATG/ALG was independently associated with a greater infection rate (IRR: 2.30, 95% CI: 1.10 to 4.81). Mortality rate (HLH 22%, leukemia 28%) and time to death post-SCT did not differ between groups. Conclusion: HLH SCT recipients have a higher infection rate in the 6 months post-HSCT compared to leukemia patients, a factor associated with pre-transplant ATG/ALG use. It is possible a difference in mortality and infection rates exists beyond the variation in ATG/ALG exposure. Further study of larger cohorts is needed. Table 1. Microbiologically Proven Infection HLH Leukemia n (%) Bacteremia Gram Positive 14 (42) 5 (35) Gram Negative 2 (6) 6 (42) Candidemia 2 (6) 0 Viral Respiratory 9 (27) 2 (14) Reactivation 6 (18) 1 (7)
    IDWeek 2014 Meeting of the Infectious Diseases Society of America; 10/2014
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    ABSTRACT: Human adenoviruses (HAdV) are known opportunistic pathogens in hematopoietic stem cell transplant (SCT) recipients. The detection of HAdV infection in children after SCT has been implicated as a determinant of poor outcome but specific associations between HAdV species or individual HAdV types and disease are poorly understood.Objectives Characterization of a HAdV-D strain isolated from multiple clinical specimens of an 11-year-old female recipient of a matched unrelated donor peripheral SCT for T-cell lymphoma and case report.Study designArchived HAdV PCR-positive plasma, urine, and stool specimens were processed for virus isolation and detailed molecular typing. Complete genomic sequencing was carried out on 2 isolates.ResultsThe patient tested positive for HAdV DNA by real-time PCR of a stool specimen at 44 days after initiation of a SCT conditioning regimen. In the subsequent 3 months, HAdV was detected in plasma, urine and stool specimens in association with symptoms of gastroenteritis and hemorrhagic cystitis. A novel HAdV-D with a HAdV20-like hexon gene was isolated from both urine and stool specimens. All isolates yielded identical restriction profiles with endonucleases BamHI, BglII, BstEII, HindIII, PstI and SmaI. Analysis of 2 complete genomic sequences further identified the virus as a novel intertypic recombinant HAdV-D (P20/H20/F42) closely related to HAdV42.Conclusions This case highlights the identification of a previously unknown HAdV-D from an immunocompromised host. In this patient, the course of adenovirus infection is compatible with reactivation of a latent virus or a primary opportunistic infection. Adenoviremia in this patient resolved without definitive adenovirus-directed antiviral therapy.
    Journal of Clinical Virology 09/2014; 61(4). DOI:10.1016/j.jcv.2014.09.009 · 3.47 Impact Factor
  • Benjamin S Chambers · Yang Li · Richard L Hodinka · Scott E Hensley
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    ABSTRACT: Prior to serological testing, influenza viruses are typically propagated in eggs or cell culture. Recent human H3N2 strains bind to cells with low avidity. Here, we isolated nine primary H3N2 viral isolates from respiratory secretions of children. Upon propagation in vitro, five of these isolates acquired hemagglutinin or neuraminidase mutations that increased virus binding to cell surfaces. These mutations can potentially confound serological assays commonly used to identify antigenically novel influenza viruses.
    Journal of Virology 07/2014; 88(18). DOI:10.1128/JVI.01077-14 · 4.65 Impact Factor
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    ABSTRACT: A 17-year-old female was admitted to our hospital with a 5-day history of fever (T max of 38.5 o C), asthenia, and nausea , accompanied by right upper quadrant abdominal pain, back pain, emesis, and jaundice during the previous 24 hours. On physical exam at the time of presentation, she was a tall and thin adolescent with a body mass index of 14.5. She was ill-appearing with scleral icterus, scant shotty cervical lymphadenopathy, and had an abdominal exam remarkable for right upper quadrant tenderness to palpa-tion. She had no appreciable hepatosplenomegaly. The rest of her physical exam was unremarkable. Results of the patient's laboratory evaluation revealed a white blood cell count (WBC) of 5100 WBC/mcL (neutro-phils 27%, bands 8%, lymphocytes 44%, monocytes 2%, eosinophils 1%, atypical lymphocytes 18%), hemoglobin of 9.9 g/dL, and platelets of 106 000/mL, normal electro-lytes, aspartate aminotransferase (AST) level of 222 U/L, alanine aminotransferase (ALT) level of 194 U/L, total bilirubin level of 11.2 mg/dL, conjugated bilirubin level of 8.7 mg/dL, albumin level of 2.8 g/dL, alkaline phospha-tase level of 130 U/L, and γ-glutamyl transferase level of 89 U/L. Electrolytes, amylase, and lipase were within normal limits. The heterophile antibody test was negative. Urinalysis showed large bilirubin, but it was otherwise normal. An abdominal ultrasound was performed, which showed a markedly and diffusely thickened gallbladder wall measuring 13 mm (Figure 1, A and B). The gallbladder lumen was collapsed with echogenic mucosa closely opposed. There were no other findings (such as pericholecystic fluid, intramural gas, sloughed mucosa, calculi, sludge, or hydrops) to suggest acalculous cholecystitis. Her past medical history was significant for long-standing poor weight gain. Despite extensive evaluations by gastroenterology, endocrinology, and genetics, no underlying etiology had been identified. Her 2 younger brothers also had a history of poor weight gain. Her immunizations were up to date and she did not take any regular medications. The patient had no history of sexual activity and denied use of tobacco, alcohol, or recreational drugs. She was born in the United States to parents who had emigrated from India. Her travel history was only remarkable for visiting India on 4 occasions, most recently 1 year prior to presentation. She had no exposure to animals and no known exposure to anyone with active tuberculosis. Her family history was significant for gallbladder disease in her mother, who underwent cholecystectomy in her mid-thirties. The patient's maternal aunt also had episodes of jaundice while living in India, with no etiology definitively identified (clinically attributed to hepatitis A virus). The patient was admitted to the gastroenterology service with a diagnosis of unspecified gallbladder disease. The differential diagnosis at that time included xanthogranu-lomatous cholecystitis, viral hepatitis, and, although rare, malignancy of the gallbladder including gallbladder
    01/2014; DOI:10.1093/jpids/piu023
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    ABSTRACT: Background: Adenovirus (HAdV) infections are associated with significant morbidity and mortality in pediatric hematopoietic stem cell transplant (HSCT) recipients. Serial HAdV polymerase chain reaction (PCR) testing is sometimes used to identify adenoviremia with a goal of early intervention. It is laborious and costly to serially test all HSCT recipients. We aimed to derive a prediction rule using data available at the time of HSCT to identify those who did and did not develop adenoviremia. An accurate prediction model could allow for more focused HAdV testing. Methods: We retrospectively identified 126 pediatric patients that: (1) received HSCT at The Children’s Hospital of Philadelphia between 2006 and 2012; and, (2) underwent surveillance HAdV PCR testing. Using stochastic gradient boosting (SGB) methodology we derived a prediction model to discriminate between those patients who did and did not develop adenoviremia in a 6-month post transplant period. To establish a balanced dataset, adenoviremic patients were compared to randomly selected controls. The model was repeated 100 times to achieve an average confusion matrix. Predictors included age, race, gender, previous HSCT, indication for HSCT, allogeneic vs. autologous HSCT, match status, stem cell source, T-cell depletion, receipt of conditioning, total body irradiation and presence of chronic comorbid conditions at time of HSCT. Results: Twenty-nine (23%) patients developed adenoviremia; median time to adenoviremia was 37 days (IQR: 20 to 69 days). No single baseline characteristic accurately discriminated those with and without adenoviremia. The best-fit SGB predictive model had a sensitivity of 75% (95% CI: 0.55 – 0.88) and specificity of 77% (95% CI: 0.57 – 0.90). The false positive and negative rates were 0.23 (95% CI: 0.10 – 0.43) and 0.25 (95% CI: 0.11 – 0.44), respectively with an average out of bag error of 0.21. Conclusion: PCR surveillance testing in pediatric HSCT recipients commonly identified adenoviremia. The derived model for predicting adenoviremia had reasonable sensitivity, specificity and out of bag error. Refining the model to include additional baseline variables such as specific conditioning medications and more adenoviremia events is necessary to reduce the false positive and false negative rates.
    IDWeek 2013 Meeting of the Infectious Diseases Society of America; 10/2013
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    Ana María Cárdenas · Eleonore Baughan · Richard L Hodinka
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    ABSTRACT: Background: In the United States, a new HIV diagnostic algorithm has been proposed that uses an HIV-1/HIV-2 antibody differentiation immunoassay instead of Western blot or immunofluoresence for confirmatory testing. Objectives: To evaluate the Multispot HIV-1/HIV-2 Rapid Test (Multispot) as an alternative to Western blot analysis for confirmation of HIV infection. Study design: A series of 205 serum and plasma specimens positive for HIV-1 or HIV-2 were used to compare the performance of Multispot to a standard HIV-1 Western blot. Positive samples included 63 specimens from patients >18 months of age, 33 proficiency survey specimens, and 109 specimens from nine commercial seroconversion and performance panels. In addition, 63 specimens from 51 HIV-exposed, uninfected children <= 18 months of age in various stages of seroreversion and 192 HIV-negative samples were tested. Specimens were initially screened using a 4th generation HIV Ag/Ab Combo assay. Results: Multi spot readily discriminated between individuals with HIV-1 or HIV-2 infection and those who were uninfected. Of the 205 samples repeatedly reactive by the 4th generation screening assay, infection status was correctly confirmed by Multispot in 83.9% (172/205) compared to 68.8% (141/205) for Western blot. Multispot detected HIV-1 earlier in 27.6% of low-titer antibody specimens called indeterminate by Western blot, and effectively reduced the number of indeterminate results in seroreverting HIV-1 exposed, uninfected infants and for HIV-2 infections misinterpreted as indeterminate or positive by HIV-1 Western blot. Conclusions: Multispot offers speed and simplicity over Western blot and has an excellent performance for differentiation and confirmation of antibodies to HIV-1 and HIV-2.
    Journal of clinical virology: the official publication of the Pan American Society for Clinical Virology 08/2013; 58. DOI:10.1016/j.jcv.2013.08.021 · 3.47 Impact Factor
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    ABSTRACT: A 15-year-old previously healthy male presented with fever, vomiting, diarrhea, malaise, and altered mental status. In the emergency department, the patient appeared acutely ill, was febrile, tachycardic, hypotensive, and slow to respond to commands. He was quickly transferred to the ICU where initial evaluation revealed elevated white blood cell count and inflammatory markers, coagulopathy, abnormal liver function, and renal failure. Head computed tomography, cerebrospinal fluid studies, and blood cultures were negative. He was quickly stabilized with intravenous fluids and broad-spectrum antibiotics. When his mental status improved, the patient consented to HIV testing and was found to be negative using laboratory-based and rapid third-generation HIV type 1 (HIV-1)/HIV type 2 antibody assays. The specimen was subsequently shown to be positive for HIV by a newly licensed fourth-generation antigen/antibody test. HIV-1 Western blot performed on this sample was negative, but molecular testing for HIV-1 RNA 4 days later was positive and confirmed the screening result. The patient was later determined to have a viral load of 5 624 053 copies/mL and subsequently admitted to unprotected receptive anal intercourse 2 weeks before admission. This case demonstrates an atypically severe presentation of acute HIV infection with important lessons for pediatricians. It highlights the need to consider acute HIV infection in the differential diagnosis of the critically ill adolescent and for appropriate testing if acute infection is suspected. This case also illustrates the shortcomings of testing adolescents based only on reported risk and supports Centers for Disease Control and Prevention and American Academy of Pediatrics recommendations for routine testing.
    PEDIATRICS 03/2013; 131(3):e959-63. DOI:10.1542/peds.2012-1533 · 5.30 Impact Factor
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    ABSTRACT: Human adenovirus (HAdV) is one of the most feared infections among immunocompromised patients. In particular, in liver transplant patients, HAdV has been implicated in acute liver failure with resultant mortality. The development of current molecular techniques and surveillance testing protocols have provided tools for early detection of HAdV infection, prior to or at the early onset of HAdV disease. Although reduction in immune suppression is the mainstay of therapy, many researchers have also advocated for early administration of antiviral therapy. In multiple reports, cidofovir treatment has been associated with declines in HAdV viral loads or clinical improvement in solid organ and bone marrow transplant recipients. However, there have also been case reports that raise questions about the effectiveness of antiviral therapy in controlling systemic HAdV disease. We report a case of a 26-month-old male recipient of a liver transplantation for hepatoblastoma who developed adenoviremia with an associated hepatitis and gastroenteritis. He recovered with reduced immune suppression but without antiviral therapy, thus avoiding potential toxicities associated with cidofovir therapy. This case a contrast to previous reports, and it highlights the ambiguity regarding which patients should receive HAdV-specific antiviral therapy. Additional knowledge regarding specific pediatric host factors and HAdV factors that predict poor outcomes are needed. Such information would allow clinicians to better stratify patients by risk at the time of adenoviremia detection so that low-risk patients are not unnecessarily exposed to medications with potential toxicities.
    02/2013; 4(1):e1-e5. DOI:10.1093/jpids/pit081
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    Richard L Hodinka · Laurent Kaiser
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    ABSTRACT: Conventional tube culture systems have long been the mainstay in clinical virology for the growth and identification of viruses from clinical specimens. Innovations such as centrifugation-enhanced shell vial and multiwell plate cultures and the use of genetically engineered and mixed cell lines coupled with a faster detection of viral replication has allowed for reasonable turn around times for even some of the most slow growing, clinically important human viruses. However, molecular methods, and in particular the polymerase chain reaction (PCR), have usurped the role of viral culture in many laboratories, limiting the use of this traditional method of virus detection or replacing it altogether. Advances and improvements in molecular technology over time have also resulted in newer generations of more rapid and accurate molecular assays for detection, quantification, and genetic characterization of viruses. In this point counterpoint, we have asked two individuals, Richard L. Hodinka of the Children's Hospital of Philadelphia, a clinical virologist whose laboratory has completely eliminated viral culture in favor of molecular methods and Laurent Kaiser, head of the Virology Laboratory at the University of Geneva Hospital, who continues to be a strong advocate for viral culture to discuss the relevance of viral culture in the molecular age.
    Journal of clinical microbiology 10/2012; 51(1). DOI:10.1128/JCM.02593-12 · 4.23 Impact Factor
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    ABSTRACT: OBJECTIVES: To determine the prevalence of central nervous system (CNS) herpes simplex virus (HSV) infection in neonates evaluated in the emergency department and to identify factors associated with cerebrospinal fluid (CSF) HSV polymerase chain reaction (PCR) testing. An existing testing paradigm was then applied to determine its potential impact on testing frequency. METHODS: This nested case-control study included infants aged 0 to 28 days who had lumbar puncture in the emergency department. Multivariate logistic regression was used to identify factors associated with CSF HSV PCR testing. RESULTS: The CSF HSV PCR testing was performed in 266 (47%) of 570 neonates. The prevalence of CNS HSV infection was 0.5% compared with 1.6% for bacterial meningitis. Performance of CSF HSV PCR testing was not associated with known HSV risk factors. Application of a known HSV testing paradigm would have reduced the proportion of infants tested by 21% without missing any of the cases of CNS HSV infection. CONCLUSIONS: The HSV testing remains common despite the low prevalence of HSV infection. The CSF HSV PCR testing is not well aligned with known risk factors. Future testing strategies should incorporate community HSV prevalence, known neonatal risk factors, and clinical judgment.
    Pediatric emergency care 09/2012; 28(10):949-955. DOI:10.1097/PEC.0b013e31826c6daf · 0.92 Impact Factor
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    Virginia M Pierce · Richard L Hodinka
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    ABSTRACT: A novel eSensor respiratory viral panel (eSensor RVP) multiplexed nucleic acid amplification test (GenMark Diagnostics, Inc., Carlsbad, CA) was compared to laboratory-developed real-time PCR assays for the detection of various respiratory viruses. A total of 250 frozen archived pediatric respiratory specimens previously characterized as either negative or positive for one or more viruses by real-time PCR were examined using the eSensor RVP. Overall agreement between the eSensor RVP and corresponding real-time PCR assays for shared analytes was 99.2% (kappa = 0.96 [95% confidence interval {CI}, 0.94 to 0.98]). The combined positive percent agreement was 95.4% (95% CI, 92.5 to 97.3); the negative percent agreement was 99.7% (95% CI, 99.4 to 99.8). The mean real-time PCR threshold cycle (C(T)) value for specimens with discordant results was 39.73 (95% CI, 38.03 to 41.43). Detection of coinfections and correct identification of influenza A virus subtypes were comparable between methods. Of note, the eSensor RVP rhinovirus assay was found to be more sensitive and specific than the corresponding rhinovirus real-time PCR. In contrast, the eSensor RVP adenovirus B, C, and E assays demonstrated some cross-reactivity when tested against known adenovirus serotypes representing groups A through F. The eSensor RVP is robust and relatively easy to perform, it involves a unique biosensor technology for target detection, and its multiplexed design allows for efficient and simultaneous interrogation of a single specimen for multiple viruses. Potential drawbacks include a slower turnaround time and the need to manipulate amplified product during the protocol, increasing the possibility of contamination.
    Journal of clinical microbiology 08/2012; 50(11):3458-65. DOI:10.1128/JCM.01384-12 · 4.23 Impact Factor
  • Virginia M Pierce · Richard L Hodinka
    Journal of clinical virology: the official publication of the Pan American Society for Clinical Virology 04/2012; 54(3):203-6. DOI:10.1016/j.jcv.2012.03.010 · 3.47 Impact Factor
  • Virginia M Pierce · Richard L Hodinka
    Journal of clinical virology: the official publication of the Pan American Society for Clinical Virology 12/2011; 53(2):93-6. DOI:10.1016/j.jcv.2011.12.003 · 3.47 Impact Factor
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    ABSTRACT: The FilmArray Respiratory Panel (RP) multiplexed nucleic acid amplification test (Idaho Technology, Inc., Salt Lake City, UT) was compared to laboratory-developed real-time PCR assays for the detection of various respiratory viruses and certain bacterial pathogens. A total of 215 frozen archived pediatric respiratory specimens previously characterized as either negative or positive for one or more pathogens by real-time PCR were examined using the FilmArray RP system. Overall agreement between the FilmArray RP and corresponding real-time PCR assays for shared analytes was 98.6% (kappa = 0.92 [95% confidence interval (CI), 0.89 to 0.94]). The combined positive percent agreement was 89.4% (95% CI, 85.4 to 92.6); the negative percent agreement was 99.6% (95% CI, 99.2 to 99.8). The mean real-time PCR threshold cycle (C(T)) value for specimens with discordant results was 36.46 ± 4.54. Detection of coinfections and correct identification of influenza A virus subtypes were comparable to those of real-time PCR when using the FilmArray RP. The greatest comparative difference in sensitivity was observed for adenovirus; only 11 of 24 (45.8%; 95% CI, 27.9 to 64.9) clinical specimens positive for adenovirus by real-time PCR were also positive by the FilmArray RP. In addition, upon testing 20 characterized adenovirus serotypes prepared at high and low viral loads, the FilmArray RP did not detect serotypes 6 and 41 at either level and failed to detect serotypes 2, 20, 35, and 37 when viral loads were low. The FilmArray RP system is rapid and extremely user-friendly, with results available in just over 1 h with almost no labor involved. Its low throughput is a significant drawback for laboratories receiving large numbers of specimens, as only a single sample can be processed at a time with one instrument.
    Journal of clinical microbiology 11/2011; 50(2):364-71. DOI:10.1128/JCM.05996-11 · 4.23 Impact Factor
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    ABSTRACT: Our objective was to analyze the pathways leading to resistance of HIV to the integrase (IN) inhibitor raltegravir (RAL). Three HIV-infected individuals exhibiting RAL resistance pathway switching were characterized using longitudinal analysis of viral samples from plasma. 454/Roche pyrosequencing was used to generate approximately 74,000 sequence reads from the integrase coding region. Effects of error were controlled by denoising with Pyronoise, and by comparison to approximately 142,000 control reads from HIV(NL4-3). Viral lineages were modeled quantitatively using viral serial pathway analysis (vSPA). All three patients showed transitions from the N155H pathway to the Q148H/G140S pathway. Analysis with vSPA revealed complex pathways to the final genotype, probably involving both de-novo mutation and recombination. No reads contained both the N155H and Q148H drug resistance mutations (DRMs), indicating that the double mutant is not a prominent intermediate, consistent with low fitness. To characterize possible drug-resistant variants circulating prior to therapy, we sequenced approximately 70,000 reads from samples collected prior to initiating treatment. Although some preexisting drug-resistant variants were detected, N155H, the first major DRM present after initiating RAL therapy, was not detected. The main DRMs are present at very low levels if at all prior to initiating therapy. We also outline general methods for deep sequence analysis of DRMs in longitudinal HIV samples.
    AIDS (London, England) 08/2011; 25(16):1951-9. DOI:10.1097/QAD.0b013e32834b34de · 6.56 Impact Factor
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    Virginia M Pierce · Brandy Neide · Richard L Hodinka
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    ABSTRACT: The Gen-Probe Aptima HIV-1 RNA qualitative assay was evaluated as an alternative to Western blot analysis for the confirmation of HIV infection using serum samples that were repeatedly reactive for HIV antibodies. The Aptima HIV assay readily discriminated between HIV-1-infected and -uninfected individuals and effectively reduced the number of indeterminate results relative to Western blot analysis.
    Journal of clinical microbiology 02/2011; 49(4):1642-5. DOI:10.1128/JCM.02183-10 · 4.23 Impact Factor
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    ABSTRACT: BACKGROUND:Cerebrospinal fluid (CSF) protein values decline over the first few months of life as the infant's blood-CSF barrier matures. However, published studies differ in the reported rate, timing, and magnitude of this decline.OBJECTIVE:To quantify the age-related changes in CSF protein concentration and to determine accurate, age-specific reference values for neonates and young infants.DESIGN, SETTING AND PATIENTS:This cross-sectional study included infants age 56 days or younger who had a lumbar puncture performed in the emergency department of an urban tertiary care children's hospital between January 1, 2005 and June 30, 2007. Infants with conditions associated with elevated CSF protein concentrations, including traumatic lumbar puncture and bacterial or viral meningitis, were excluded.RESULTS:Of 1064 infants undergoing lumbar puncture, 375 (35%) met inclusion criteria. The median CSF protein value was 58 mg/dL (interquartile range: 48–72 mg/dL). In linear regression, the CSF protein concentration decreased 6.8% (95% confidence interval [CI], 5.4%-8.1%; P < 0.001) with each 1 week increase in age. The 95th percentile values were 115 mg/dL for infants ≤28 days and 89 mg/dL for infants 29–56 days. The 95th percentile values by age category were as follows: ages 0–14 days, 132 mg/dL; ages 15–28 days, 100 mg/dL; ages 29–42 days, 89 mg/dL; and ages 43–56 days, 83 mg/dL.CONCLUSIONS:We quantify the age-related decline in CSF protein concentration among infants 56 days of age and younger and provide age-specific reference values. The values reported here represent the largest series to-date for this age group. Journal of Hospital Medicine 2011. © 2010 Society of Hospital Medicine.
    Journal of Hospital Medicine 01/2011; 6(1):22 - 27. DOI:10.1002/jhm.711 · 2.08 Impact Factor
  • Adriana E Kajon · Laura M Dickson · Brian T Fisher · Richard L Hodinka
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    ABSTRACT: The use of corticosteroids and other immunosuppressive agents increases the risk of infection in patients with systemic lupus erythematosus (SLE). The role of human adenoviruses (HAdV) in the etiology of acute viral diseases in these patients is not known. Describe a case of acute fatal disseminated adenovirus infection in an SLE patient receiving immunosuppressive therapy. Case report and detailed viral diagnosis by real time PCR and molecular typing of virus isolates by sequencing of hexon and fiber genes and restriction enzyme analysis of viral DNA. HAdV was detected by real time PCR in multiple clinical specimens including respiratory, urine, plasma, synovial fluid, and cerebrospinal fluid. Amplification and sequence analysis of the hexon and fiber genes identified the virus as HAdV-7-like for both coding regions. Adenoviruses isolated from respiratory and urine specimens were identical and corresponded to genome type 7d2 by restriction enzyme analysis of viral DNA. The isolated strain encodes a unique fiber gene with a 6-nucleotide deletion corresponding to amino acid positions 250 and 251 in the knob region and not previously described for closely related genomic variants of HAdV-7. Adenovirus detection should be included in the diagnostic testing to determine the infectious etiology of fever and/or respiratory symptoms in SLE patients.
    Journal of clinical virology: the official publication of the Pan American Society for Clinical Virology 11/2010; 50(1):80-3. DOI:10.1016/j.jcv.2010.09.021 · 3.47 Impact Factor

Publication Stats

2k Citations
375.88 Total Impact Points

Institutions

  • 1993–2015
    • The Children's Hospital of Philadelphia
      • • Department of Pathology and Laboratory Medicine
      • • Division of Infectious Diseases
      • • Department of Pediatrics
      Filadelfia, Pennsylvania, United States
  • 2013
    • University of Pennsylvania
      • Department of Pathology and Laboratory Medicine
      Philadelphia, Pennsylvania, United States
  • 2010
    • William Penn University
      Filadelfia, Pennsylvania, United States
  • 2001
    • United States Department of Defense
      Arlington, Virginia, United States
  • 1992
    • Hospital of the University of Pennsylvania
      • Department of Pathology and Laboratory Medicine
      Philadelphia, Pennsylvania, United States