Pedro A Piedra

Baylor College of Medicine, Houston, Texas, United States

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Publications (101)515.63 Total impact

  • The Journal of infectious diseases. 08/2014;
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    ABSTRACT: Background Bronchiolitis is the leading cause of hospitalization in infants. Biomarkers of disease severity might help in clinical management.Objective To determine the clinical predictiveness of NW-LDH, NW-caspase 3/7, and NW-LDH/NW-caspase 3/7 ratio in bronchiolitis.Methods Previously healthy children less than 24 months of age with bronchiolitis were recruited from the Texas Children's emergency room and intensive care unit from October 2010 to April 2011. Demographic, clinical information, and NW samples were obtained at enrollment. NW samples were analyzed for respiratory viruses, caspase 3/7, and LDH.ResultsA viral pathogen was detected in 91·6% of 131 children, with the most common being respiratory syncytial virus and human rhinovirus. A single infection was found in 61·8% of subjects and co-infection in 29·8%. Children admitted to ICU had significantly higher NW-LDH than children sent home from the ER or admitted to the general floor (P = 0·02). Children infected with RSV had the highest NW-LDH concentration (P = 0·03) compared with other viral infections. NW-LDH and NW-caspase were significantly correlated (r = 0·77, P < 0·0001). The univariate models showed NW-LDH and NW-LDH/NW- caspase 3/7 ratio were directly associated with hospitalization. Mutivariate regression analyses suggested a complex interaction between the biomarkers, demographics, and disposition.ConclusionsNW-LDH, NW-caspase 3/7 and NW-LDH/NW-caspase 3/7 ratio and their interactions with demographic factors are predictive of bronchiolitis severity and can help distinguish children requiring ICU-level care from those admitted to the general floor, or discharged home from the emergency center.
    Influenza and Other Respiratory Viruses 08/2014; · 1.47 Impact Factor
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    ABSTRACT: Bronchiolitis is the leading cause of hospitalization for US infants and is associated with increased risk of childhood asthma. Although studies have shown differences in the presentation and management of asthma across race/ethnicity, it is unclear if such differences are present for bronchiolitis. We examined if racial/ethnic differences exist in the presentation and management of severe bronchiolitis.
    Journal of Hospital Medicine 06/2014; · 1.40 Impact Factor
  • Pedro A Piedra, Flor M Munoz
    The Journal of infectious diseases. 06/2014;
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    ABSTRACT: Respiratory syncytial virus (RSV) can cause devastating lower respiratory tract infections in preterm infants or when other serious health problems are present. Immunoprophylaxis with palivizumab (Synagis), a humanized IgG1 mAb, is the current standard of care for preventing RSV infection in at-risk neonates. We have explored the contribution of effector function to palivizumab efficacy using a plant-based expression system to produce palivizumab N-glycan structure variants with high homogeneity on different antibody isotypes. We compared these isotype and N-glycoform variants with commercially available palivizumab with respect to both in vitro receptor and C1q binding and in vivo efficacy. Whereas the affinity for antigen and neutralization activity of each variant were indistinguishable from those of palivizumab, their Fcγ receptor binding profiles were very different, which was reflected in either a reduced or enhanced ability to influence the RSV lung titer in challenged cotton rats. Enhanced Fcγ receptor binding was associated with reduced viral lung titers compared with palivizumab, whereas abrogation of receptor binding led to a drastic reduction in efficacy. The results support the hypotheses that classic antibody neutralization is a minor component of efficacy by palivizumab in the cotton rat and that antibody-dependent cell-mediated cytotoxicity activity can significantly enhance the efficacy of this antiviral mAb.
    Proceedings of the National Academy of Sciences 04/2014; · 9.74 Impact Factor
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    ABSTRACT: The lack of a vaccine against respiratory syncytial virus (RSV) is a challenging and serious gap in preventive medicine. Herein, we characterize the immunogenicity and protection following immunization with an adenoviral-based RSV vaccine encoding for the fusion protein F (Ad5.RSV-F) and assess its potential for producing enhanced disease in a cotton rat (CR) model. Animals were immunized intranasally (IN) and/or intramuscularly (IM) and subsequently challenged with RSV/A/Tracy (IN) to assess protection. Robust immune responses were seen in CRs vaccinated with Ad5.RSV-F given IM or IN, which correlated with reduced replication of virus in noses and lungs after challenge. Neutralizing antibody responses following immunization with a single dose of Ad5.RSV-F at 1×10(11) viral particles (v.p.) elicited antibody titers 64- to 256- fold greater than those seen after natural infection. CRs boosted with Ad5.RSV-F IN 28 days after an IM dose also had significant increases in neutralizing antibody titers. Antibody affinity for different F protein antigenic sites revealed substantial differences between antibodies elicited by Ad5.RSV-F as compared with those seen after RSV infection; differences in antibody profiles were also seen in CRs given Ad5.RSV-F IM vs. IN. Ad5.RSV-F priming did not result in enhanced disease following live virus challenge in contrast with histopathology seen in CRs given formalin-inactivated-RSV/A/Burnett vaccine. Respiratory syncytial virus (RSV) is the most common cause of acute lower respiratory infection in infants and young children and a serious health threat in the immunocompromised and the elderly. Infection severity increased in children in an immunization trial, hampering the over four decades-long quest for a successful RSV vaccine. In this study, we show that a genetically-engineered RSV-F encoding adenoviral vector provides protective immunity against RSV challenge without enhanced lung disease in cotton rats (CRs). CRs were vaccinated under a number of different regimens and intramuscular-intranasal prime-boost immunity induced by the recombinant adenoviral RSV vaccine may provide the best protection for young infants and children at risk of RSV infection, since this population is naïve to adenoviral preformed immunity. Overall, this manuscript describes a potential RSV vaccine candidate that merits further evaluation in a phase I clinical study in humans.
    Journal of Virology 02/2014; · 5.08 Impact Factor
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    ABSTRACT: It is unclear whether the infectious etiology of severe bronchiolitis affects short-term outcomes, such as post-hospitalization relapse. We tested the hypothesis that children hospitalized with rhinovirus (RV) bronchiolitis, either as a sole pathogen or in combination with respiratory syncytial virus (RSV), are at increased risk of relapse. We performed a 16-center, prospective cohort study of hospitalized children age <2 years with bronchiolitis. During the winters of 2007 to 2010, researchers collected clinical data and nasopharyngeal aspirates from study participants; the aspirates were tested using real-time polymerase chain reaction. The primary outcome was bronchiolitis relapse (urgent bronchiolitis visit or scheduled visit at which additions to the bronchiolitis medications were made) during the 2 weeks after hospital discharge. Among 1836 enrolled children with 2-week follow-up data, the median age was 4 months and 60% were male. Overall, 48% had sole RSV infection, 8% had sole RV infection, and 13% had RSV/RV co-infection. Compared with children with sole RSV infection, and adjusting for 10 demographic and clinical characteristics and clustering of patients within hospitals, children with sole RV infection did not differ in their likelihood of relapse (OR, 0.99; 95%CI, 0.52-1.90; P=0.98), whereas those with RSV/RV co-infection were more likely to have relapse (OR, 1.54; 95%CI, 1.03-2.30; P=0.03). In this prospective, multicenter, multiyear study of children hospitalized with bronchiolitis, we found that RSV/RV co-infection was independently associated with a higher likelihood of bronchiolitis relapse. Present data support the concept that the infectious etiology of severe bronchiolitis affects short-term outcomes.
    The Pediatric Infectious Disease Journal 02/2014; · 3.57 Impact Factor
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    ABSTRACT: Among 20 children admitted with laboratory-confirmed influenza, viral RNA was detected in respiratory secretion, stool and blood in 19, 5 and 1 children, respectively. Gastrointestinal symptoms were common but were not associated with viral RNA in stool. nH1N1 viremia was detected, for the first time, in an immunocompetent child.
    The Pediatric Infectious Disease Journal 01/2014; 33(1):95-96. · 3.57 Impact Factor
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    ABSTRACT: Human respiratory syncytial virus (HRSV) has three surface glycoproteins: small hydrophobic (SH), attachment (G) and fusion (F), encoded by three consecutive genes (SH-G-F). A 270-nt fragment of the G gene is used to genotype HRSV isolates. This study genotyped and investigated the variability of the gene and amino acid sequences of the three surface proteins of HRSV strains collected from 1987 to 2005 from one center. Sixty original clinical isolates and 5 prototype strains were analyzed. Sequences containing SH, F and G genes were generated, and multiple alignments and phylogenetic trees were analyzed. Genetic variability by protein domains comparing virus genotypes was assessed. Complete sequences of the SH-G-F genes were obtained for all 65 samples: HRSV-A = 35; HRSV-B = 30. In group A strains, genotypes GA5 and GA2 were predominant. For HRSV-B strains, the genotype GB4 was predominant from 1992 to 1994 and only genotype BA viruses were detected in 2004-2005. Different genetic variability at nucleotide level was detected between the genes, with G gene being the most variable and the highest variability detected in the 270-nt G fragment that is frequently used to genotype the virus. High variability (>10%) was also detected in the signal peptide and transmembrane domains of the F gene of HRSV A strains. Variability among the HRSV strains resulting in non-synonymous changes was detected in hypervariable domains of G protein, the signal peptide of the F protein, a not previously defined domain in the F protein, and the antigenic site Ø in the pre-fusion F. Divergent trends were observed between HRSV -A and -B groups for some functional domains. A diverse population of HRSV -A and -B genotypes circulated in Houston during an 18 year period. We hypothesize that diverse sequence variation of the surface protein genes provide HRSV strains a survival advantage in a partially immune-protected community.
    PLoS ONE 01/2014; 9(3):e90786. · 3.73 Impact Factor
  • The Journal of allergy and clinical immunology 12/2013; · 12.05 Impact Factor
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    ABSTRACT: Background. Each year, the US Flu VE Network examines the effectiveness of influenza vaccines in preventing medically-attended acute respiratory illnesses caused by influenza. Methods. Patients with acute respiratory illnesses of <7 days duration were enrolled at ambulatory care facilities in five communities. Specimens were collected and tested for influenza by real-time reverse transcriptase polymerase chain reaction. Receipt of influenza vaccine was defined based on documented evidence of vaccination in medical records or immunization registries. Vaccine effectiveness was estimated in adjusted logistic regression models by comparing the vaccination coverage in those who tested positive for influenza with those who tested negative. Results. The 2011-2012 season was mild and peaked late, with circulation of both type A viruses and both lineages of type B. Overall adjusted vaccine effectiveness was 47% (95% confidence interval [CI], 36 to 56) in preventing medically-attended influenza; vaccine effectiveness was 65% (95% CI, 44 to 79) against type A (H1N1) pdm09, but only 39% (95% CI, 23 to 52) against type A (H3N2). Estimates of vaccine effectiveness against both type B lineages were similar (overall 58%, 95% CI, 35 to 73). An apparent negative effect of prior year vaccination on current year effectiveness estimates was noted, particularly for A (H3N2) outcomes. Conclusions. Vaccine effectiveness in the 2011-2012 season was modest overall, with lower effectiveness against the predominant A (H3N2) virus. This may be related to modest antigenic drift, but past history of vaccination might also play a role.
    Clinical Infectious Diseases 11/2013; · 9.37 Impact Factor
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    ABSTRACT: OBJECTIVE:To identify risk factors for inpatient apnea among children hospitalized with bronchiolitis.METHODS:We enrolled 2207 children, aged <2 years, hospitalized with bronchiolitis at 16 sites during the winters of 2007 to 2010. Nasopharyngeal aspirates (NPAs) were obtained on all subjects, and real-time polymerase chain reaction was used to test NPA samples for 16 viruses. Inpatient apnea was ascertained by daily chart review, with outcome data in 2156 children (98%). Age was corrected for birth <37 weeks. Multivariable logistic regression was performed to identify independent risk factors for inpatient apnea.RESULTS:Inpatient apnea was identified in 108 children (5%, 95% confidence interval [CI] 4%-6%). Statistically significant, independent predictors of inpatient apnea included: corrected ages of <2 weeks (odds ratio [OR] 9.67) and 2 to 8 weeks (OR 4.72), compared with age ≥6 months; birth weight <2.3 kg (5 pounds; OR 2.15), compared with ≥3.2 kg (7 pounds); caretaker report of previous apnea during this bronchiolitis episode (OR 3.63); preadmission respiratory rates of <30 (OR 4.05), 30 to 39 (OR 2.35) and >70 (OR 2.26), compared with 40 to 49; and having a preadmission room air oxygen saturation <90% (OR 1.60). Apnea risk was similar across the major viral pathogens.CONCLUSIONS:In this prospective, multicenter study of children hospitalized with bronchiolitis, inpatient apnea was associated with younger corrected age, lower birth weight, history of apnea, and preadmission clinical factors including low or high respiratory rates and low room air oxygen saturation. Several bronchiolitis pathogens were associated with apnea, with similar apnea risk across the major viral pathogens.
    PEDIATRICS 10/2013; · 4.47 Impact Factor
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    ABSTRACT: BACKGROUND: Adult community-acquired pneumonia (CAP) is a relevant worldwide cause of morbidity and mortality, however the aetiology often remains uncertain and the therapy is empirical. We applied conventional and molecular diagnostics to identify viruses and atypical bacteria associated with CAP in Chile. METHODS: We used sputum and blood cultures, IgG/IgM serology and molecular diagnostic techniques (PCR, reverse transcriptase PCR) for detection of classical and atypical bacteria (Mycoplasma pneumoniae, Chlamydia pneumoniae, Legionella pneumoniae) and respiratory viruses (adenovirus, respiratory syncytial virus (RSV), human metapneumovirus, influenza virus, parainfluenzavirus, rhinovirus, coronavirus) in adults >18 years old presenting with CAP in Santiago from February 2005 to September 2007. Severity was qualified at admission by Fine's pneumonia severity index. RESULTS: Overall detection in 356 enrolled adults were 92 (26%) cases of a single bacterial pathogen, 80 (22%) cases of a single viral pathogen, 60 (17%) cases with mixed bacterial and viral infection and 124 (35%) cases with no identified pathogen. Streptococcus pneumoniae and RSV were the most common bacterial and viral pathogens identified. Infectious agent detection by PCR provided greater sensitivity than conventional techniques. To our surprise, no relationship was observed between clinical severity and sole or coinfections. CONCLUSIONS: The use of molecular diagnostics expanded the detection of viruses and atypical bacteria in adults with CAP, as unique or coinfections. Clinical severity and outcome were independent of the aetiological agents detected.
    Thorax 06/2013; · 8.38 Impact Factor
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    ABSTRACT: BACKGROUND: When novel influenza viruses cause human infections, it is critical to characterize the illnesses, viruses, and immune responses to infection in order to develop diagnostics, treatments, and vaccines. The objective of the study was to collect samples from patients with suspected or confirmed A(H1N1)pdm09 infections that could be made available to the scientific community. Respiratory secretions, sera and peripheral blood mononuclear cells (PBMCs) were collected sequentially (when possible) from patients presenting with suspected or previously confirmed A(H1N1)pdm09 infections. Clinical manifestations and illness outcomes were assessed. Respiratory secretions were tested for the presence of A(H1N1)pdm09 virus by means of isolation in tissue culture and real time RT-PCR. Sera were tested for the presence and level of HAI and neutralizing antibodies against the A(H1N1)pdm09 virus.Findings and conclusions: Thirty patients with confirmed A(H1N1)pdm09 infection were enrolled at Baylor College of Medicine (BCM). Clinical manifestations of illness were consistent with typical influenza. Twenty-eight of 30 had virological confirmation of illness; all recovered fully. Most patients had serum antibody responses or high levels of antibody in convalescent samples. Virus-positive samples were sent to J. Craig Venter Institute for sequencing and sequences were deposited in GenBank. Large volumes of sera collected from 2 convalescent adults were used to standardize antibody assays; aliquots of these sera are available from the repository. Aliquots of serum, PBMCs and stool collected from BCM subjects and subjects enrolled at other study sites are available for use by the scientific community, upon request.
    BMC Research Notes 05/2013; 6(1):177.
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    ABSTRACT: Severe lower respiratory tract infection in infants and small children is commonly caused by respiratory syncytial virus (RSV). Palivizumab (Synagis (®) ), a humanized IgG 1 monoclonal antibody (mAb) approved for RSV immunoprophylaxis in at-risk neonates, is highly effective, but pharmacoeconomic analyses suggest its use may not be cost-effective. Previously described potent RSV neutralizers (human Fab R19 and F2-5; human IgG RF-1 and RF-2) were produced in IgG format in a rapid and inexpensive Nicotiana-based manufacturing system for comparison with palivizumab. Both plant-derived (palivizumab-N) and commercial palivizumab, which is produced in a mouse myeloma cell line, showed protection in prophylactic (p < 0.001 for both mAbs) and therapeutic protocols (p < 0.001 and p < 0.05 respectively). The additional plant-derived human mAbs directed against alternative epitopes displayed neutralizing activity, but conferred less protection in vivo than palivizumab-N or palivizumab. Palivizumab remains one of the most efficacious RSV mAbs described to date. Production in plants may reduce manufacturing costs and improve the pharmacoeconomics of RSV immunoprophylaxis and therapy.
    mAbs 02/2013; 5(2). · 5.28 Impact Factor
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    ABSTRACT: BACKGROUND:: Respiratory syncytial virus (RSV) is a leading cause of pediatric lower respiratory tract infections and has a high impact on pediatric emergency department (ED) utilization. Variation in host response may influence the pathogenesis and disease severity. We evaluated global gene expression profiles to better understand the systemic host response to acute RSV bronchiolitis in infants and young children. METHODS:: Patients (age ≤ 24 months) who were clinically diagnosed with acute bronchiolitis and who had a positive rapid test for RSV assay were recruited from the Texas Children's Hospital ED. Global gene expression of peripheral whole blood cells were analyzed in 21 cases and 37 age-matched healthy controls. Transcripts exhibiting significant upregulation and downregulation as a result of RSV infection were identified and confirmed in a subset of samples using RNAseq. The potential pathways affected were analyzed. RESULTS:: Blood was obtained from patients with acute RSV bronchiolitis (mean age 6 months). Of these, 43% were admitted to the hospital, 52% were given intravenous fluids and 24% received oxygen. Highly significant expression differences were detected in a discovery cohort of White infants (N=33) and validated in an independent group of African American infants (N=19). Individuals with mild disease (N=15) could not be distinguished from subjects with clinically moderate disease (N=5). Pathway enrichment analyses of the differentially expressed genes demonstrated extensive activation of the innate immune response, particularly the interferon signaling network. There was a significant downregulation of transcripts corresponding to antigen presentation.
    The Pediatric Infectious Disease Journal 11/2012; · 3.57 Impact Factor
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    ABSTRACT: OBJECTIVE: We performed a Phase 1 randomized, observer-blinded, placebo-controlled trial to evaluate the safety and immunogenicity of a recombinant respiratory syncytial virus (RSV) fusion (F) protein nanoparticle vaccine. METHODS: Six formulations with (5, 15, 30 and 60μg) and without (30 and 60μg) aluminum phosphate (AdjuPhos) were administered intramuscularly on day 0 and 30 in a dose escalating fashion to healthy adults 18-49 years of age. Solicited and unsolicited events were collected through day 210. Immunogenicity measures taken at day 0, 30 and 60 included RSV A and B microneutralization, anti-F IgG, antigenic site II peptide and palivizumab competitive antibodies. RESULTS: The vaccine was well-tolerated, with no evident dose-related toxicity or attributable SAEs. At day 60 both RSV A and B microneutralization was significantly increased in vaccinees versus placebo. Across all vaccinees there was a 7- to 19-fold increase in the anti-F IgG and a 7- to 24-fold increase in the antigenic site II binding and palivizumab competitive antibodies. CONCLUSIONS: The RSV F nanoparticle vaccine candidate was well tolerated without dose-related increases in adverse events. Measures of immunity indicate that neutralization, anti-RSV F IgG titers and palivizumab competing antibodies were induced at levels that have been associated with decreased risk of hospitalization. NCT01290419.
    Vaccine 11/2012; · 3.77 Impact Factor
  • The Journal of allergy and clinical immunology 08/2012; 130(4):1007-1008.e1. · 12.05 Impact Factor
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    ABSTRACT: To identify factors associated with continuous positive airway pressure (CPAP) and/or intubation for children with bronchiolitis. We performed a 16-center, prospective cohort study of hospitalized children aged <2 years with bronchiolitis. For 3 consecutive years from November 1 until March 31, beginning in 2007, researchers collected clinical data and a nasopharyngeal aspirate from study participants. We oversampled children from the ICU. Samples of nasopharyngeal aspirate were tested by polymerase chain reaction for 18 pathogens. There were 161 children who required CPAP and/or intubation. The median age of the overall cohort was 4 months; 59% were male; 61% white, 24% black, and 36% Hispanic. In the multivariable model predicting CPAP/intubation, the significant factors were: age <2 months (odds ratio [OR] 4.3; 95% confidence interval [CI] 1.7-11.5), maternal smoking during pregnancy (OR 1.4; 95% CI 1.1-1.9), birth weight <5 pounds (OR 1.7; 95% CI 1.0-2.6), breathing difficulty began <1 day before admission (OR 1.6; 95% CI 1.2-2.1), presence of apnea (OR 4.8; 95% CI 2.5-8.5), inadequate oral intake (OR 2.5; 95% CI 1.3-4.3), severe retractions (OR 11.1; 95% CI 2.4-33.0), and room air oxygen saturation <85% (OR 3.3; 95% CI 2.0-4.8). The optimism-corrected c-statistic for the final model was 0.80. In this multicenter study of children hospitalized with bronchiolitis, we identified several demographic, historical, and clinical factors that predicted the use of CPAP and/or intubation, including children born to mothers who smoked during pregnancy. We also identified a novel subgroup of children who required mechanical respiratory support <1 day after respiratory symptoms began.
    PEDIATRICS 08/2012; 130(3):e492-500. · 4.47 Impact Factor
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    ABSTRACT: We reexamined the finding of an inverse relationship between values of nasopharyngeal lactate dehydrogenase, a marker of the innate immune response, and bronchiolitis severity. In a prospective, multicenter study of 258 children, we found in a multivariable model that higher nasopharyngeal lactate dehydrogenase values in young children with bronchiolitis were independently associated with a decreased risk of hospitalization.
    The Pediatric Infectious Disease Journal 04/2012; 31(7):767-9. · 3.57 Impact Factor

Publication Stats

4k Citations
515.63 Total Impact Points

Institutions

  • 1991–2014
    • Baylor College of Medicine
      • • Department of Pediatrics
      • • Department of Molecular Virology & Microbiology
      • • Department of Medicine
      Houston, Texas, United States
  • 2013
    • Santa Clara Valley Medical Center
      San Jose, California, United States
  • 2012
    • Novavax
      Maryland, United States
    • Harvard Medical School
      • Department of Medicine
      Boston, MA, United States
    • Boston Children's Hospital
      Boston, Massachusetts, United States
  • 2010
    • United BioSource Corporation
      Maryland, United States
  • 2008
    • Scott & White
      Temple, Texas, United States
  • 2007
    • Fred Hutchinson Cancer Research Center
      • Biostatistics and Biomathematics Program
      Seattle, WA, United States
    • Cincinnati Children's Hospital Medical Center
      • Division of Emergency Medicine
      Cincinnati, OH, United States
  • 2004
    • Texas A&M University System Health Science Center
      • Pediatrics
      Bryan, Texas, United States
    • Stanford University
      • Department of Microbiology and Immunology
      Palo Alto, CA, United States
    • American Society of Gene & Cell Therapy
      Houston, Texas, United States
  • 2003
    • Seoul National University
      • Department of Pediatrics
      Seoul, Seoul, South Korea
    • Emory University
      • Department of Biostatistics and Bioinformatics
      Atlanta, GA, United States
  • 2000
    • University of Missouri - St. Louis
      Saint Louis, Michigan, United States
  • 1998–2000
    • Saint Louis University
      • School of Medicine
      Saint Louis, MI, United States
  • 1995
    • University at Buffalo, The State University of New York
      Buffalo, New York, United States