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1.
Thorax ; 75(10): 882-890, 2020 10.
Article in English | MEDLINE | ID: mdl-32820081

ABSTRACT

BACKGROUND: Differences in clinical impact between rhinovirus (RVs) species and types in adults are not well established. The objective of this study was to determine the epidemiology and clinical impact of the different RV species. METHODS: We conducted a prospective study of RVs infections in adults with acute cough/lower respiratory tract infection (LRTI) and asymptomatic controls. Subjects were recruited from 16 primary care networks located in 11 European countries between 2007 and 2010. RV detection and genotyping was performed by means of real time and conventional reverse-transcriptase polymerase chain reaction assays, followed by sequence analysis. Clinical data were obtained from medical records and patient symptom diaries. RESULTS: RVs were detected in 566 (19%) of 3016 symptomatic adults, 102 (4%) of their 2539 follow-up samples and 67 (4%) of 1677 asymptomatic controls. Genotyping was successful for 538 (95%) symptomatic subjects, 86 (84%) follow-up infections and 62 (93%) controls. RV-A was the prevailing species, associated with an increased risk of LRTI as compared with RV-B (relative risk (RR), 4.5; 95% CI 2.5 to 7.9; p<0.001) and RV-C (RR 2.2; 95% CI 1.2 to 3.9; p=0.010). In symptomatic subjects, RV-A loads were higher than those of RV-B (p=0.015). Symptom scores and duration were similar across species. More RV-A infected patients felt generally unwell in comparison to RV-C (p=0·023). Of the 140 RV types identified, five were new types; asymptomatic infections were associated with multiple types. INTERPRETATION: In adults, RV-A is significantly more often detected in cases with acute cough/LRTI than RV-C, while RV-B infection is often found in asymptomatic patients.


Subject(s)
Epidemics , Picornaviridae Infections/epidemiology , Respiratory Tract Infections/epidemiology , Respiratory Tract Infections/virology , Rhinovirus/genetics , Seasons , Adult , Europe/epidemiology , Female , Humans , Male , Middle Aged , Molecular Epidemiology , Picornaviridae Infections/diagnosis , Prospective Studies , Respiratory Tract Infections/diagnosis
3.
PLoS One ; 9(9): e108018, 2014.
Article in English | MEDLINE | ID: mdl-25268349

ABSTRACT

BACKGROUND: Congenital cytomegalovirus infection is a leading cause of long-term sequelae. Cytomegalovirus is also frequently transmitted to preterm infants postnatally, but these infections are mostly asymptomatic. A correlation between cytomegalovirus genotypes and clinical manifestations has been reported previously in infants with congenital infection, but not in preterm infants with postnatal infection. OBJECTIVES: The main objective of this study was to investigate cytomegalovirus genotype distribution in postnatal and congenital cytomegalovirus infection and its association with disease severity. METHODS: Infants admitted to the neonatal intensive care unit of the University Medical Center Utrecht, The Netherlands between 2003-2010 and diagnosed with postnatal or congenital cytomegalovirus infection were included. Classification of cytomegalovirus isolates in genotypes was performed upon amplification and sequencing of the cytomegalovirus UL55 (gB) and UL144 genes. Clinical data, cerebral abnormalities, neurodevelopmental outcome and viral load were studied in relation to genotype distribution. RESULTS: Genotyping results were obtained from 58 preterm infants with postnatal cytomegalovirus infection and 13 infants with congenital cytomegalovirus infection. Postnatal disease was mild in all preterm infants and all had favourable outcome. Infants with congenital infection were significantly more severely affected than infants with postnatal infection. Seventy-seven percent of these infants were symptomatic at birth, 2/13 died and 3/13 developed long-term sequelae (median follow-up 6 (range 2-8) years). The distribution of cytomegalovirus genotypes was comparable for postnatal and congenital infection. UL55 genotype 1 and UL144 genotype 3 were predominant genotypes in both groups. CONCLUSIONS: Distribution of UL55 and UL144 genotypes was similar in asymptomatic postnatal and severe congenital CMV infection suggesting that other factors rather than cytomegalovirus UL55 and UL144 genotype are responsible for the development of severe disease.


Subject(s)
Cross Infection/pathology , Cytomegalovirus Infections/pathology , Cytomegalovirus/genetics , Genotype , Child , Child, Preschool , Cross Infection/virology , Cytomegalovirus/classification , Cytomegalovirus/isolation & purification , Cytomegalovirus Infections/congenital , Cytomegalovirus Infections/mortality , Cytomegalovirus Infections/virology , Female , Humans , Infant , Infant, Newborn , Infant, Premature , Longitudinal Studies , Male , Membrane Glycoproteins/genetics , Netherlands , Severity of Illness Index , Survival Analysis , Viral Envelope Proteins , Viral Load , Viral Proteins/genetics
4.
Eur Respir J ; 44(1): 169-77, 2014 Jul.
Article in English | MEDLINE | ID: mdl-24876172

ABSTRACT

Rhinovirus infections occur frequently throughout life and have been reported in about one-third of asymptomatic cases. The clinical significance of sequential rhinovirus infections remains unclear. To determine the incidence and clinical relevance of sequential rhinovirus detections, nasopharyngeal samples from 2485 adults with acute cough/lower respiratory illness were analysed. Patients were enrolled prospectively by general practitioners from 12 European Union countries during three consecutive years (2007-2010). Nasopharyngeal samples were collected at the initial general practitioner consultation and 28 days thereafter and symptom scores were recorded by patients over that period. Rhinovirus RNA was detected in 444 (18%) out of 2485 visit one samples and in 110 (4.4%) out of 2485 visit two respiratory samples. 21 (5%) of the 444 patients had both samples positive for rhinovirus. Genotyping of both virus detections was successful for 17 (81%) out of 21 of these patients. Prolonged rhinovirus shedding occurred in six (35%) out of 21 and re-infection with a different rhinovirus in 11 (65%) out of 21. Rhinovirus re-infections were significantly associated with chronic obstructive pulmonary disease (p=0.04) and asthma (p=0.02) and appeared to be more severe than prolonged infections. Our findings indicate that in immunocompetent adults rhinovirus re-infections are more common than prolonged infections, and chronic airway comorbidities might predispose to more frequent rhinovirus re-infections.


Subject(s)
Picornaviridae Infections/virology , Respiratory Tract Infections/virology , Rhinovirus , Virus Shedding , Adult , Aged , Bacterial Infections/complications , Comorbidity , Drug Resistance, Viral , European Union , Female , Genotype , Humans , Male , Middle Aged , Molecular Typing , Picornaviridae Infections/epidemiology , Prospective Studies , Respiratory Tract Infections/epidemiology , Treatment Outcome , Young Adult
5.
Ther Drug Monit ; 35(4): 546-51, 2013 Aug.
Article in English | MEDLINE | ID: mdl-23851908

ABSTRACT

BACKGROUND: Correlations between ribavirin (RBV) concentrations and sustained virological response (SVR) to hepatitis C virus treatment have been demonstrated previously. As steady state is reached after several weeks of RBV treatment, dose modifications based on steady-state levels can only be applied relatively late in treatment, possibly too late to influence SVR rates. The authors aimed to determine whether measurement of early concentrations is useful to predict optimal steady-state RBV concentrations. METHODS: In 61 treatment-naive genotype 1/4 patients RBV concentrations were determined in samples collected after 1, 2, 4, 8, 12, and 24 weeks of therapy. RBV concentrations were compared between responders and nonresponders; Receiver Operating Characteristic analyses were conducted to find optimal cut-off values to predict week 8 concentrations from earlier measurements. RESULTS: Median week 8 RBV concentrations were significantly higher in patients with SVR compared with those without: 3.4 (interquartile range 2.4-3.9) versus 2.6 (interquartile range 2.0-3.5) mg/L (P < 0.05). RBV concentration at week 8 was an independent predictor of SVR [adjusted odds ratio 2.3 (95% confidence interval: 1.1-4.9; P = 0.03)]. The optimal cut-off value of week 8 RBV concentration to predict SVR was 2.20 mg/L [sensitivity 87%, specificity 40%, positive predictive value 64%, negative predictive value 71%]. Optimal cut-off values at weeks 1, 2, or 4 to predict an RBV concentration ≥2.20 mg/L at week 8 were 0.92, 1.29, and 1.67 mg/L, respectively, with positive predictive values and negative predictive values ranging from 88% to 91% and 71% to 86%, respectively. CONCLUSIONS: RBV concentrations in the earliest stages of antiviral therapy predict therapeutic steady-state concentrations, allowing timely dose adjustments with potential implications for treatment outcome.


Subject(s)
Antiviral Agents/blood , Antiviral Agents/therapeutic use , Hepacivirus/drug effects , Hepatitis C/blood , Hepatitis C/drug therapy , Ribavirin/blood , Ribavirin/therapeutic use , Adult , Double-Blind Method , Female , Genotype , Humans , Male , Treatment Outcome
6.
Sex Transm Dis ; 40(8): 650-1, 2013 Aug.
Article in English | MEDLINE | ID: mdl-23863516

ABSTRACT

BACKGROUND: Anogenital warts are one of the most prevalent sexually transmitted virus infections in the Netherlands and cause frustration, shame, and even depression. This study was performed to determine the effect of having anogenital warts on the quality of life in Dutch soldiers with the use of a dermatology-specific quality of life (QoL) questionnaire. METHODS: We used the Skindex-29 QoL questionnaire in 100 predominantly heterosexual soldiers with clinically confirmed first episode of condylomata acuminate in this study. RESULTS: Results confirmed that first episodes of anogenital warts cause high mean scores on subscale Emotions with lower scores on the subscales Symptoms and Functioning. Sex, age, educational level, anatomical site, or number of anatomical sites did not influence the outcome in this study. CONCLUSIONS: Having anogenital warts influences QoL, especially with regard to intimacy, shame, and concern. Our data show that the Skindex-29 QoL questionnaire can be easily used in these patients with good internal consistency. Clinicians should be aware of the great emotional impact of anogenital warts on their patients.


Subject(s)
Anus Diseases/epidemiology , Condylomata Acuminata/epidemiology , Military Personnel , Papillomavirus Infections/epidemiology , Quality of Life , Sexual Behavior/statistics & numerical data , Adolescent , Adult , Anus Diseases/psychology , Condylomata Acuminata/psychology , Female , Health Knowledge, Attitudes, Practice , Humans , Information Seeking Behavior , Male , Military Personnel/psychology , Military Personnel/statistics & numerical data , Netherlands/epidemiology , Papillomavirus Infections/psychology , Patient Acceptance of Health Care/statistics & numerical data , Risk-Taking , Self Concept , Surveys and Questionnaires
7.
Invest Ophthalmol Vis Sci ; 54(5): 3709-20, 2013 May 01.
Article in English | MEDLINE | ID: mdl-23633652

ABSTRACT

PURPOSE: To investigate the presence of biomarkers in aqueous humor (AH) from patients with uveitis associated with juvenile idiopathic arthritis (JIA). METHODS: AH (N = 73) AND SERUM (N = 105) SAMPLES FROM 116 CHILDREN WERE ANALYZED USING SURFACE ENHANCED LASER DESORPTION/IONIZATION TIME OF FLIGHT MASS SPECTROMETRY (SELDI-TOF MS). THE SAMPLES WERE DIVIDED INTO THE FOLLOWING GROUPS: JIA, silent chronic anterior uveitis (AU), other uveitis entities, and noninflammatory controls. Statistical biomarker identification was performed using the SELDI-ToF Biomarker Analysis Cluster Wizard followed by multivariate statistical analysis. Biochemical identification of biomarkers was performed by polyacrylamide gel protein separation, followed by liquid chromatography tandem mass spectrometry. ELISA was performed in a number of AH samples representing all four study groups. RESULTS: In the JIA group, one AH protein peak at mass/charge (m/z) 13,762 had qualitative and quantitative differences in expression compared with the other uveitis entities and the controls, but not to the group of silent chronic AU. Its quantitative expression in AH of patients with JIA and other silent chronic AU was positively associated with uveitis activity. The protein at m/z 13,762 in AH was identified as transthyretin (TTR). The TTR concentration in AH differed significantly between the study groups (P = 0.006) with considerably higher TTR concentrations in JIA and silent chronic AU samples positive for m/z 13,762 than those of the other uveitis and control groups. CONCLUSIONS: TTR is a potential intraocular biomarker of JIA- associated uveitis. Its role in the pathogenesis of silent chronic AU with and without arthritis needs further investigation.


Subject(s)
Aqueous Humor/metabolism , Arthritis, Juvenile/complications , Arthritis, Juvenile/metabolism , Proteomics , Uveitis , Adolescent , Biomarkers/metabolism , Cataract/metabolism , Child , Child, Preschool , Female , Glaucoma/metabolism , Humans , Infant , Male , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization , Uveitis/diagnosis , Uveitis/etiology , Uveitis/metabolism , Young Adult
8.
J Virol Methods ; 190(1-2): 53-62, 2013 Jun.
Article in English | MEDLINE | ID: mdl-23458694

ABSTRACT

During September and October 2010, the Dutch Public Health Institute detected an enterovirus (EV) 68 (EV68) epidemic in the Netherlands through general practitioner-based surveillance of acute respiratory infections. EV68 shares phenotypic and genotypic properties with human rhinovirus (HRV). Despite increased EV and HRV detections, Dutch clinical laboratories did not identify EV68. To assess the capability of Dutch clinical laboratories to detect EV68, ten laboratories with more than eight detected EV and HRV cases in September and October 2010 provided information about their detection algorithms and testing results for a 2010 Dutch EV68 strain. For EV detection mostly stool specimens (median 49%), respiratory specimens (median 27%) and cerebrospinal fluid (median 22%) were used. For HRV detection only respiratory specimens were used. Except for the Seeplex® RV15ACE EV-specific assay, all EV and 73% of HRV assays, including those of the Public Health Institute, were able to detect EV68. Two-step EV RT-PCR protocols were the most sensitive. Thus, laboratories might have misidentified EV68 as HRV. In addition, EV68 cases might have also been missed because patients with respiratory diseases are usually not tested for EV infection. Therefore, clinical laboratories should include EV detection in the differential diagnosis of patients presenting with respiratory symptoms.


Subject(s)
Clinical Laboratory Techniques/methods , Clinical Laboratory Techniques/standards , Enterovirus Infections/diagnosis , Enterovirus/isolation & purification , Respiratory Tract Infections/diagnosis , Cerebrospinal Fluid/virology , Enterovirus Infections/virology , Feces/virology , Humans , Laboratory Proficiency Testing , Netherlands , Respiratory Tract Infections/virology , Sensitivity and Specificity , Sputum/virology
9.
J Med Virol ; 85(4): 689-95, 2013 Apr.
Article in English | MEDLINE | ID: mdl-23296599

ABSTRACT

Immunological mechanisms influencing the risk of mother-to-child cytomegalovirus (CMV) transmission in preterm infants have not been studied sufficiently. In this study, the correlation between maternal and neonatal serum anti-CMV IgG levels and risk of postnatal CMV transmission in preterm infants was assessed. Anti-CMV IgG levels of 79 CMV seropositive mothers and their 94 infants were determined in peripheral blood samples collected within 3 days after delivery. Postnatal CMV infection was detected in 39/94 (41%) infants by PCR on urine at term-equivalent age (gestational age 40 weeks) after congenital infection was excluded. Maternal or infant anti-CMV IgG levels were not significantly different between infants with and without postnatal CMV infection. The anti-CMV IgG infant-mother ratio showed a significant positive correlation with gestational age (range 25-32 weeks, R(2) = 0.218, P < 0.001), reaching 1.0 at 32 weeks of gestation. Anti-CMV IgG infant-mother ratio was significantly lower in infants with postnatal CMV infection (P = 0.015). In conclusion, the risk of postnatal CMV transmission is related to low gestational age and low anti-CMV IgG infant-mother ratio.


Subject(s)
Antibodies, Viral/blood , Cytomegalovirus Infections/transmission , Cytomegalovirus/immunology , Immunoglobulin G/blood , Infectious Disease Transmission, Vertical , Pregnancy Complications, Infectious/immunology , Pregnancy Complications, Infectious/virology , Adult , Cytomegalovirus/isolation & purification , Cytomegalovirus Infections/diagnosis , Female , Humans , Infant, Newborn , Infant, Premature , Male , Pregnancy , Risk Assessment , Urine/virology , Young Adult
10.
PLoS One ; 7(12): e51439, 2012.
Article in English | MEDLINE | ID: mdl-23236501

ABSTRACT

Human respiratory syncytial virus (RSV) is an important cause of severe lower respiratory tract infections in infants and the elderly. In the vast majority of cases, however, RSV infections run mild and symptoms resemble those of a common cold. The immunological, clinical, and epidemiological profile of severe RSV infections suggests a disease caused by a virus with typical seasonal transmission behavior, lacking clear-cut virulence factors, but instead causing disease by modifying the host's immune response in a way that stimulates pathogenesis. Yet, the interplay between RSV-evoked immune responses and epidemic behavior, and how this affects the genomic evolutionary dynamics of the virus, remains poorly understood. Here, we present a comprehensive collection of 33 novel RSV subgroup A genomes from strains sampled over the last decade, and provide the first measurement of RSV-A genomic diversity through time in a phylodynamic framework. In addition, we map amino acid substitutions per protein to determine mutational hotspots in specific domains. Using Bayesian genealogical inference, we estimated the genomic evolutionary rate to be 6.47 × 10(-4) (credible interval: 5.56 × 10(-4), 7.38 × 10(-4)) substitutions/site/year, considerably slower than previous estimates based on G gene sequences only. The G gene is however marked by elevated substitution rates compared to other RSV genes, which can be attributed to relaxed selective constraints. In line with this, site-specific selection analyses identify the G gene as the major target of diversifying selection. Importantly, statistical analysis demonstrates that the immune driven positive selection does not leave a measurable imprint on the genome phylogeny, implying that RSV lineage replacement mainly follows nonselective epidemiological processes. The roughly 50 years of RSV-A genomic evolution are characterized by a constant population size through time and general co-circulation of lineages over many epidemic seasons - a conclusion that might be taken into account when developing future therapeutic and preventive strategies.


Subject(s)
Evolution, Molecular , Genetic Variation/genetics , Genome, Viral/genetics , Respiratory Syncytial Virus Infections/epidemiology , Respiratory Syncytial Virus, Human/genetics , Selection, Genetic , Amino Acid Substitution/genetics , Base Sequence , Bayes Theorem , Belgium/epidemiology , Child, Preschool , DNA Primers/genetics , Genomics/methods , Humans , Infant , Infant, Newborn , Models, Genetic , Molecular Sequence Data , Mutation Rate , Netherlands/epidemiology , Real-Time Polymerase Chain Reaction , Respiratory Syncytial Virus Infections/virology , Sequence Analysis, DNA , Viral Envelope Proteins/genetics
11.
J Clin Virol ; 54(2): 121-4, 2012 Jun.
Article in English | MEDLINE | ID: mdl-22421537

ABSTRACT

BACKGROUND: A correlation between cytomegalovirus (CMV) load in urine and severity of disease in congenitally infected infants has previously been reported. CMV load in postnatally infected infants has not been studied before. OBJECTIVE: To investigate CMV load in urine of infants with postnatal or congenital infection and correlate this with clinical symptoms of CMV disease and cerebral abnormalities. STUDY DESIGN: Infants admitted to our NICU between July 2000 and February 2010, and diagnosed with congenital or postnatal CMV infection were included. Clinical symptoms of CMV infection, cranial ultrasonography (cUS) and magnetic resonance imaging (MRI) findings were evaluated. CMV urine loads of postnatally infected infants were analyzed and compared with CMV urine loads of congenitally infected infants. RESULTS: Seventeen infants with congenital CMV infection and 45 infants with postnatal CMV infection were included. Thirteen/17 (76%) congenitally infected infants had clinical symptoms of CMV infection at birth and 11/17 (65%) had cerebral abnormalities diagnosed by neuro-imaging. None of the four asymptomatic infants had cerebral abnormalities. Of the postnatally infected infants 43/45 (96%) did not develop any clinical symptoms of CMV infection, but in 23/45 (51%) cerebral abnormalities such as lenticulostriate vasculopathy and germinolytic cysts were identified. The median CMV load in postnatally infected infants was significantly lower than in congenitally infected infants (1.0×10(5)copies/ml versus 8.5×10(6)copies/ml, p<0.001, respectively). CONCLUSIONS: CMV load in urine is significantly lower in infants with postnatal CMV infection than in infants with congenital CMV infection irrespective of clinical symptoms of CMV infection or cerebral abnormalities.


Subject(s)
Cytomegalovirus Infections/congenital , Cytomegalovirus Infections/diagnosis , Cytomegalovirus/isolation & purification , Urine/virology , Viral Load , Brain/diagnostic imaging , Cytomegalovirus Infections/pathology , Encephalitis, Viral/congenital , Encephalitis, Viral/diagnosis , Encephalitis, Viral/pathology , Female , Head/diagnostic imaging , Humans , Infant , Infant, Newborn , Magnetic Resonance Imaging , Male , Radiography , Severity of Illness Index , Ultrasonography
12.
Arch Dis Child Fetal Neonatal Ed ; 97(4): F259-63, 2012 Jul.
Article in English | MEDLINE | ID: mdl-22247412

ABSTRACT

OBJECTIVE: To study risk factors and cranial ultrasound (cUS) findings in a large cohort of preterm infants, admitted to a neonatal intensive care unit and diagnosed with postnatally acquired cytomegalovirus (CMV) infection. STUDY DESIGN: This prospective, observational study was performed from April 2007 until June 2009 among 315 infants born <32 weeks of gestation. Postnatal CMV infection was diagnosed by CMV PCR on urine collected at term-equivalent age. In CMV-positive infants, congenital infection was excluded. The authors compared the clinical and demographic data, feeding pattern and cUS results of infected and non-infected patients. Logistic regression analysis was performed. RESULTS: In 39 of 315 infants, the diagnosis of postnatal CMV infection has been made. The majority of CMV-infected infants (33/39.85%) did not develop any symptoms of CMV infection. The most important, independent risk factors of postnatal CMV infection were non-native Dutch maternal origin (OR 9.6 (95% CI 4.3 to 21.5)) and breast milk (OR 13.2 (95% CI 1.7 to 104.5)). The risk of infection significantly increased in infants with lower gestational age (GA) (OR 0.7 (95% CI 0.5 to 0.9)). Lenticulostriate vasculopathy (LSV) was significantly more often present in infants with CMV infection (OR 4.1 (95% CI 1.9 to 8.8)). CONCLUSIONS: Postnatal CMV infection is an asymptomatic infection among preterm infants. Infants with lower GA are at greatest risk of postnatal CMV infection, especially when fed with fresh breast milk from their non-native Dutch mother. LSV not present at birth but confirmed at term-equivalent age can suggest a postnatal CMV infection.


Subject(s)
Basal Ganglia Cerebrovascular Disease/diagnostic imaging , Cytomegalovirus Infections/etiology , Infant, Premature, Diseases/etiology , Basal Ganglia Cerebrovascular Disease/virology , Birth Weight , Breast Feeding/adverse effects , Cytomegalovirus Infections/complications , Cytomegalovirus Infections/diagnostic imaging , Cytomegalovirus Infections/transmission , Echoencephalography/methods , Female , Gestational Age , Humans , Infant, Newborn , Infant, Premature , Infant, Premature, Diseases/diagnostic imaging , Infectious Disease Transmission, Vertical , Intensive Care Units, Neonatal , Male , Milk, Human/virology , Prospective Studies , Risk Factors
13.
J Pediatr ; 160(1): 165-8.e1, 2012 Jan.
Article in English | MEDLINE | ID: mdl-21982304

ABSTRACT

We describe 5 preterm and 3 term infants who presented with seizures during rotavirus infection within 6 weeks after birth. Six of these infants developed late-onset cystic periventricular leukomalacia. Four of the preterm infants had neurodevelopmental delay, and 4 (near) term infants had normal early outcome.


Subject(s)
Leukomalacia, Periventricular/virology , Rotavirus Infections/complications , Female , Humans , Infant, Newborn , Male
14.
Antivir Ther ; 16(4): 611-4, 2011.
Article in English | MEDLINE | ID: mdl-21685550

ABSTRACT

A 14 year old common variable immunodeficiency patient developed severe protein-losing enteropathy. A chronic enteral infection with human parechovirus type 1 and norovirus was diagnosed. Treatment strategies aimed at virus eradication and providing supportive care were ineffective. The antipicornavirus agent pleconaril did not have any effect on viral replication. Symptoms improved on immunosuppressive therapy, suggesting infection-related immune dysregulation in an immunocompromised host.


Subject(s)
Agammaglobulinemia/complications , Antiviral Agents/pharmacology , Drug Resistance, Viral , Oxadiazoles/pharmacology , Parechovirus/drug effects , Picornaviridae Infections/virology , Protein-Losing Enteropathies/virology , Adolescent , Caliciviridae Infections/complications , Caliciviridae Infections/virology , Chronic Disease , Feces/virology , Humans , Immunocompromised Host , Male , Norovirus/isolation & purification , Oxazoles , Parechovirus/isolation & purification
15.
Pediatr Pulmonol ; 46(5): 428-34, 2011 May.
Article in English | MEDLINE | ID: mdl-21194137

ABSTRACT

RATIONALE FOR THE STUDY: Real-time polymerase chain reaction (PCR) for respiratory viruses is more sensitive, yet more expensive, than conventionally used direct immunofluorescence (DIF). We determined the impact of real-time PCR, additional to DIF, on antibiotic prescription in ventilated children with lower respiratory tract infection (LRTI) at admission to the pediatric intensive care unit (PICU). METHODS: First, a multicenter survey study was performed. Subsequently, in a prospective study, children (≤ 5 years) with LRTI were tested at admission by DIF and PCR. Positive DIF results were reported at the end of the first working day. PICU physicians reported antibiotic treatment on the second working day. After informing them of the PCR result antibiotic treatment was reevaluated. RESULTS: The multicenter survey study (94 respondents) showed that PCR decreased antibiotic use (P < 0.001). In the prospective study 38 children were included, of which 19 (50%) were DIF positive. Of the 19 DIF negative patients 12 (63%) were treated with antibiotics before revealing the PCR result; the PCR test was positive in 9 out of 12. Revealing PCR results did not alter antibiotic treatment. In 7 DIF negative patients antibiotics not given, the PCR test was positive. CONCLUSION: In contrast to their responses to the survey study, in real-life PICU physicians did not let their antibiotic prescription be influenced by respiratory real-time PCR in children ventilated for LRTI.


Subject(s)
Anti-Bacterial Agents/therapeutic use , DNA, Viral/analysis , Respiratory Tract Infections/drug therapy , Virus Diseases/drug therapy , Child, Preschool , Female , Hospitalization , Humans , Infant , Infant, Newborn , Intensive Care Units, Pediatric , Male , Practice Patterns, Physicians' , Prospective Studies , Real-Time Polymerase Chain Reaction , Respiratory Tract Infections/virology , Virus Diseases/virology
16.
Am J Ophthalmol ; 150(5): 628-36, 2010 Nov.
Article in English | MEDLINE | ID: mdl-20691420

ABSTRACT

PURPOSE: To determine infectious causes in patients with uveitis of unknown origin by intraocular fluids analysis. DESIGN: Case-control study. METHODS: Ocular fluids from 139 patients suspected of infectious uveitis, but negative for herpes simplex virus, varicella-zoster virus, cytomegalovirus, and Toxoplasma gondii by polymerase chain reaction and/or antibody analysis in intraocular fluids, were assessed for the presence of 18 viruses and 3 bacteria by real-time polymerase chain reaction (PCR). The ocular fluids from 48 patients with uveitis of known etiology or with cataract were included as controls. RESULTS: Positive PCR results were found for Epstein-Barr virus, for rubella virus, and for human herpesvirus 6 each in 1 patient and for human parechovirus in 4 patients. Of the human parechovirus-positive patients, 1 was immunocompromised and had panuveitis. The other 3 patients were immunocompetent and had anterior uveitis, all with corneal involvement. CONCLUSIONS: Human parechovirus might be associated with infectious (kerato)uveitis.


Subject(s)
Aqueous Humor/virology , Eye Infections, Viral/virology , Herpesvirus 4, Human/isolation & purification , Herpesvirus 6, Human/isolation & purification , Parechovirus/isolation & purification , Rubella virus/isolation & purification , Uveitis, Anterior/virology , Adult , Aged , Antibodies, Viral/blood , Case-Control Studies , DNA Primers/chemistry , DNA, Viral/analysis , Enzyme-Linked Immunosorbent Assay , Epstein-Barr Virus Infections/diagnosis , Epstein-Barr Virus Infections/virology , Eye Infections, Viral/diagnosis , Female , Fluorescent Antibody Technique, Indirect , Herpesvirus 4, Human/genetics , Herpesvirus 6, Human/genetics , Humans , Male , Middle Aged , Parechovirus/genetics , Picornaviridae Infections/diagnosis , Picornaviridae Infections/virology , Polymerase Chain Reaction , Retrospective Studies , Roseolovirus Infections/diagnosis , Roseolovirus Infections/virology , Rubella/diagnosis , Rubella/virology , Rubella virus/genetics
17.
J Clin Microbiol ; 48(10): 3569-74, 2010 Oct.
Article in English | MEDLINE | ID: mdl-20660210

ABSTRACT

Quantitative real-time PCR for the detection of respiratory syncytial virus (RSV) RNA is increasingly used to study the causal role of RSV in lower airway disease. The objective of our study was to evaluate variations in RSV RNA loads at different steps in the RNA quantification process: (i) variation in RSV RNA load within one sample (step 1), (ii) variation in the load in samples from patients who were sampled twice on the same day (step 2), and (iii) variation in the load between simultaneously taken nasopharyngeal aspirate (NPA) samples and tracheal aspirate (TA) samples (step 3). Thirty-two infants with RSV infection at the pediatric intensive care unit (PICU) were included. NPA and TA samples were taken three times a week during ventilation and were not diluted. Intrasample variation (step 1) was shown to be minimal (<0.5 log(10) particles/ml). Intraday variation (step 2) was the lowest for samples with high viral loads (95% limits of agreement, -1.3 to +0.9 log(10)), whereas it increased for samples with relatively lower viral loads (viral load, <6.0 log(10) particles/ml; n = 138 sample pairs from 20 patients). RSV loads in NPA and TA samples (step 3) were found to be the most comparable during the early phase of infection (95% limits of agreement, -1.5 to +1.4 log(10)). The variation increased during the late phase of infection (i.e., in follow-up samples), with the loads in NPA samples remaining significantly higher than the loads in TA samples (n = 138 sample pairs from 31 patients). In conclusion, quantitative detection of RSV RNA in undiluted mucus is a reliable method to quantify viral loads. Nasopharyngeal aspirate samples collected in the initial phase of infection can be used to predict RSV RNA loads in the lower airways.


Subject(s)
RNA, Viral/genetics , Respiratory Syncytial Virus Infections/virology , Respiratory Syncytial Virus, Human/isolation & purification , Reverse Transcriptase Polymerase Chain Reaction/methods , Viral Load , Virology/methods , Humans , Infant , Mucus/virology , Nasopharynx/virology , Trachea/virology
18.
Arch Dis Child Fetal Neonatal Ed ; 95(3): F206-12, 2010 May.
Article in English | MEDLINE | ID: mdl-20444813

ABSTRACT

OBJECTIVE: To assess the severity of the disease and the long-term cardiac prognosis for neonates who developed enterovirus (EV) myocarditis within the first weeks of life. DESIGN: Clinical presentation, echocardiographic and ECG findings and the outcome of seven infants with EV myocarditis admitted to the intensive care unit are reported. Additionally, 28 previously reported cases are described. RESULTS: Seven neonates presented with cardiac failure within 17 days after birth requiring respiratory and circulatory support. Echocardiography showed dilatation and severe dysfunction of the left ventricle in all and mitral regurgitation in six. In six patients the echocardiographic pattern resembled myocardial infarction. ECG showed complete loss of the R-wave and a new Q-wave in the left precordial leads in all. Two infants died and five developed long-term cardiac sequelae requiring medication. In all survivors aneurysm formation in the left ventricular wall was found weeks to months later. One patient is awaiting heart transplantation. Coxsackie virus B was detected in blood, cerebrospinal fluid, nasopharyngeal swab or stool by PCR or culture. The mortality of previously described neonates combined with our seven cases was 31% (11/35). Among the survivors 66% (16/24) developed severe cardiac damage. Only 23% (8/35) of the infants fully recovered. CONCLUSIONS: EV myocarditis is a rare but severe disease in the neonatal period, which often leads to death or results in serious chronic cardiac sequelae like chronic heart failure, aneurysm formation within the left ventricle and mitral regurgitation. Chronic cardiac drug therapy is necessary in the majority of these patients.


Subject(s)
Enterovirus B, Human/isolation & purification , Enterovirus Infections/diagnosis , Myocarditis/virology , Cardiomyopathy, Dilated/virology , Electrocardiography , Enterovirus Infections/complications , Enterovirus Infections/diagnostic imaging , Female , Follow-Up Studies , Heart Aneurysm/virology , Humans , Infant, Newborn , Male , Myocarditis/diagnosis , Myocarditis/diagnostic imaging , Prognosis , Ultrasonography
19.
Pediatr Transplant ; 14(4): 520-8, 2010 Jun.
Article in English | MEDLINE | ID: mdl-20345613

ABSTRACT

HAdV infection is a dangerous complication after pediatric SCT. In this study, we aimed at determining the cytokine profile in plasma samples in case of HAdV infection after SCT to gain more knowledge about the HAdV-specific immune response. In this prospective study, 47 pediatric SCT recipients were included in three yr. By using particle-based MIA, 17 different cytokines were analyzed in 41 plasma samples of patients with a localized HAdV infection (presence of HAdV in feces, urine or throat detected by culture) and patients with invasive HAdV infection (HAdV viremia in blood, detected by PCR). In patients with invasive HAdV infection, but not in patients with localized HAdV infection, the pro-inflammatory cytokines IL1beta, IL6, IL8, IL12, IFNgamma, TNFalpha, and also IL17, MIP1alpha, OSM, and IP10 were produced. The simultaneous release of the cytokines IL1beta, IL17, IL18, OSM, MIP1alpha, and IP10 was related to invasive HAdV infections. We also show that cytokine signatures can be helpful to differentiate invasive HAdV infection from GvHD and EBV infections. In conclusion, after SCT, children with invasive HAdV infection have a different cytokine profile compared with patients with a localized HAdV infection.


Subject(s)
Adenovirus Infections, Human/blood , Cytokines/blood , Postoperative Complications/blood , Stem Cell Transplantation , Adenovirus Infections, Human/immunology , Adolescent , Biomarkers/blood , Child , Child, Preschool , Cytokines/immunology , Enzyme-Linked Immunosorbent Assay , Female , Humans , Infant , Male , Polymerase Chain Reaction , Postoperative Complications/immunology , Prospective Studies , Statistics, Nonparametric , Viremia/immunology
20.
Pediatr Infect Dis J ; 29(4): 364-5, 2010 Apr.
Article in English | MEDLINE | ID: mdl-19935443

ABSTRACT

Data of 11 infants (median gestational age and birth weight 30 weeks and 1520 g, respectively) with severe human rhinovirus infection (HRV) are described. Nine of 11 (82%) were preterm infants and 7 of these 9 (78%) became infected during their stay in the neonatal intensive care unit. All infants presented with respiratory distress and all needed respiratory support for a median of 6 days. Radiologic findings included perihilar streakiness, atelectasis, focal consolidation, and hyperinflation. The diagnosis of HRV infection was made by real-time polymerase chain reaction in nasopharyngeal aspirate. All infants recovered from their HRV infection. HRV can cause severe disease in preterm infants requiring respiratory support.


Subject(s)
Infant, Low Birth Weight , Infant, Premature, Diseases/physiopathology , Lung Diseases/physiopathology , Picornaviridae Infections/physiopathology , Rhinovirus/pathogenicity , Humans , Infant, Newborn , Infant, Premature , Infant, Premature, Diseases/virology , Intensive Care Units, Neonatal/statistics & numerical data , Lung Diseases/virology , Nasopharynx/virology , Picornaviridae Infections/virology , Polymerase Chain Reaction/methods , Rhinovirus/classification , Rhinovirus/genetics , Rhinovirus/isolation & purification , Severity of Illness Index
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