Molecular epidemiology and clinical impact of rhinovirus infections in adults during three epidemic seasons in 11 European countries (2007-2010).

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.

Prolonged shedding of rhinovirus and re-infection in adults with respiratory tract illness.

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.

Maternal and neonatal anti-cytomegalovirus IgG level and risk of postnatal cytomegalovirus transmission in preterm infants.

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.

Anogenital warts: influence on quality of life in Dutch soldiers.

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.

Measuring ribavirin concentrations during the earliest stages of antiviral therapy for hepatitis C: potential relevance for treatment outcome.

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.

Development of cystic periventricular leukomalacia in newborn infants after rotavirus infection.

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.

Lack of CD200 enhances pathological T cell responses during influenza infection.

Influenza virus infection can be accompanied by life-threatening immune pathology most likely due to excessive antiviral responses. Inhibitory immune receptors may restrain such overactive immune responses. To study the role of the inhibitory immune receptor CD200R and its ligand CD200 during influenza infection, we challenged wild-type and CD200(-/-) mice with influenza virus. We found that CD200(-/-) mice in comparison to wild-type controls when inoculated with influenza virus developed more severe disease, associated with increased lung infiltration and lung endothelium damage. CD200(-/-) mice did develop adequate adaptive immune responses and were able to control viral load, suggesting that the severe disease was caused by a lack of control of the immune response. Interestingly, development of disease was completely prevented by depletion of T cells before infection, despite dramatically increased viral load, indicating that T cells are essential for the development of disease symptoms. Our data show that lack of CD200-CD200R signaling increases immune pathology during influenza infection, which can be reduced by T cell depletion.

Molecular quantification of respiratory syncytial virus in respiratory samples: reliable detection during the initial phase of infection.

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.

Dynamics of human respiratory virus-specific CD8+ T cell responses in blood and airways during episodes of common cold.

We determined the dynamics of CD8(+) T cells specific for influenza virus and respiratory syncytial virus in blood and tracheostoma aspirates of children during the course of respiratory infections. We showed that during localized respiratory infections the ratio of activated effector CD8(+) T cells to resting memory/naive CD8(+) T cells in peripheral blood increased significantly. Furthermore, the number of effector/memory T cells specific for respiratory viruses declined in blood and increased in the airways, suggesting that these T cells redistributed from blood to airways. T cells specific for the infecting virus were present in the airways for longer periods at increased levels than nonspecifically recruited bystander T cells. After clearance of the infection, the ratio of resting memory and naive CD8(+) T cells normalized in peripheral blood and also memory T cell numbers specific for unrelated viruses that declined during the infection due to bystander recruitment were restored. Taken together, these results showed a significant systemic T cell response during relatively mild secondary infections and extensive dynamics of virus-specific and nonspecific Ag-experienced T cells.

Different cytokine signatures in children with localized and invasive adenovirus infection after stem cell transplantation.

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.

Human bocavirus and KI/WU polyomaviruses in pediatric intensive care patients.

We evaluated the prevalence of human bocavirus and KI and WU polyomaviruses in pediatric intensive care patients with and without lower respiratory tract infection (LRTI). The prevalence of these viruses was 5.1%, 0%, and 2.6%, respectively, in children with LRTI and 4.8%, 4.8%, and 2.4%, respectively, in those without LRTI.

Human parechovirus causes encephalitis with white matter injury in neonates.

OBJECTIVE: To assess the role of human parechoviruses (HPeVs) as a cause of neonatal cerebral infection and to report neuroimaging findings of newborn infants with encephalitis caused by HPeVs. METHODS: Clinical presentation, cranial ultrasonography, magnetic resonance imaging (MRI) findings, and neurodevelopmental outcome of 10 infants admitted to a neonatal intensive care unit and diagnosed with encephalitis caused by HPeVs are reported. RESULTS: Nine of 10 infants, with a gestational age of 29 to 41 weeks, presented at 36 to 41 weeks postmenstrual age with clinical seizures. Seven had a fever and six had a rash. Clinical presentation was similar to that of infants with enterovirus infection. Cranial ultrasonography showed increased echogenicity in the periventricular white matter in all infants. Neonatal MRI confirmed white matter changes in nine infants, which changed to gliosis on later MRI. Outcome was variable with cerebral palsy in one, a suspect outcome at 18 months in one, learning disabilities at 7 years of age in one, epilepsy in one, and normal neurodevelopmental outcome in five children. Follow-up of one infant was only 9 months. INTERPRETATION: HPeVs should be added to the list of neurotropic viruses that may cause severe central nervous system infection in the neonatal period. White matter injury can be visualized with cranial ultrasonography, but more detailed information is obtained with MRI and especially diffusion-weighted imaging. Because clinical presentation of HPeV encephalitis is similar to that of enterovirus, real-time polymerase chain reaction for both viruses should be performed in atypical presentation of neonatal seizures.

Human herpes virus 6 plasma DNA positivity after hematopoietic stem cell transplantation in children: an important risk factor for clinical outcome.

Human herpes virus 6 (HHV6) is known to reactivate after hematopoietic stem cell transplantation (HSCT), and has been suggested to be associated with severe clinical manifestations in adults. The clinical significance in children remains unclear. We investigated the incidence of HHV6 reactivation in relation to HSCT-associated morbidity and mortality in children. Between January 2004 and May 2006, 58 pediatric patients, median age 7.6 years (range: 0.1-18.1 years), received their first allogeneic HSCT. After HSCT, HHV6, Epstein Barr Virus (EBV), cytomegalovirus (CMV), and adenovirus (AdV)-plasma loads were weekly measured by quantitative PCR. Clinical features, engraftment, graft-versus-host disease (GVHD), and HSCT-associated mortality and morbidity were monitored. HHV6 reactivations were classified in group I (no reactivation), group II (loads <1000 cp/mL) and group III (loads >1000 cp/mL). CMV, EBV, Herpes Simpex Virus, Varicella Zoster Virus, and AdV-reactivations were treated according to local guidelines. HHV6 was treated only when there was clinical suspicion of disease. Thirty-six HLA-identical and 22 HLA nonidentical grafts were transplanted of which 43 were bone marrow or peripheral blood stem cells grafts and 15 were cord blood (CB) grafts. Median follow-up of the patients was 15.5 (1-35) months. HHV6 reactivation occurred in 39 of 58 (67%) patients with 31 of 39 (80%) occurring within the first 30 days post-HSCT. In 26 of 58 (45%) patients (group III), HHV 6 reactivation was significantly associated with higher nonrelapse mortality (P = .02), using multivariate Cox proportional hazard models and grade 2-4 acute GVHD (P = .03) and chronic GVHD (P = .05) in a multivariate logistic regression analysis. HHV6 reactivation is very common after HSCT in children and is associated with serious transplantation-related morbidity and mortality. Although the exact role of HHV6 reactivation after HSCT has to be elucidated, early detection and initiation of therapy might be of benefit.

Effects of influenza plus pneumococcal conjugate vaccination versus influenza vaccination alone in preventing respiratory tract infections in children: a randomized, double-blind, placebo-controlled trial.

OBJECTIVE: To evaluate the effects of influenza vaccination with or without heptavalent pneumococcal conjugate vaccination on respiratory tract infections (RTIs) in children. STUDY DESIGN: This was a randomized, double-blind, placebo-controlled trial comprising 579 children age 18 to 72 months with a previous history of physician-diagnosed RTI, recruited between 2003 and 2005. The children were assigned to 2 doses of parenteral inactivated trivalent subunit influenza plus heptavalent pneumococcal conjugate vaccination (TIV+PCV7), influenza plus placebo vaccination (TIV+plac), or control hepatitis B virus vaccination plus placebo (HBV+plac). Main outcome measures were febrile RTI and related polymerase chain reaction (PCR)-confirmed influenza, primary care visits, antibiotic prescriptions, and acute otitis media (AOM) episodes. RESULTS: During influenza seasons, febrile RTI were reduced by 24% (95% confidence interval [CI] = 1% to 42%) in the TIV+PCV7 group and by 13% (95% CI = -12% to 32%) in the TIV+plac group compared with the control group. The occurrence of PCR-confirmed influenza was reduced by 52% (95% CI = 7% to 75%) in the TIV+PCV7 group and by 51% (95% CI = 3% to 75%) in the TIV+plac group. Episodes of AOM were reduced by 57% (95% CI = 6% to 80%) in the TIV+PCV7 group and by 71% (95% CI = 30% to 88%) in the TIV+plac group. Outside of the influenza seasons, no significant effects of vaccinations were demonstrated on the studied outcomes. CONCLUSIONS: During influenza seasons, influenza vaccination with or without pneumococcal conjugate vaccination substantially reduced cases of confirmed influenza and AOM episodes.

External quality assessment of cytomegalovirus DNA detection on dried blood spots.

BACKGROUND: Testing for viral DNA in neonatal blood dried on paper (DBS) has proved a valid means of diagnosing congenital CMV infection with both clinical and epidemiological relevance. To assess the quality of the detection of CMV-DNA on DBS in laboratories performing this test a proficiency panel consisting of nine samples with two blood spots on each filter paper was produced and distributed. Six samples were derived from whole blood, negative for CMV DNA and antibody, and spiked with cell-grown CMV Towne in various concentrations (7.3 x 102 - 9.6 x 105 copies/ml), one was a CMV positive clinical specimen (3.9 x 106 copies/ml), and two samples were CMV-negative whole blood. RESULTS: The 27 responding laboratories from 14 countries submitted 33 datasets obtained by means of conventional PCR (n = 5) or real-time PCR (n = 28) technologies. A correct positive result was reported in at least 91% of datasets in samples with a viral load of 8.8 x 104 copies/ml or higher. However only 59% and 12% identified the 9.4 x 103 and 7.3 x 102 copies/ml samples, respectively, correctly as positive. False positive results were reported by 9% of laboratories and in 11% of datasets. CONCLUSION: These results indicate a clear need for improvement of methods as sensitivity and false-positivity still appear to be a major problem in a considerable number of laboratories.

Usefulness of aqueous humor analysis for the diagnosis of posterior uveitis.

PURPOSE: To assess the clinical usefulness of aqueous fluid analysis for the diagnosis and treatment of patients suspected of having infectious posterior uveitis (PU). DESIGN: Case-control study. PARTICIPANTS: From 2002 through 2005, 152 eyes from 152 patients with active PU (16 of whom were immunosuppressed) underwent diagnostic aqueous testing. As controls, 20 patients with Fuchs' heterochromic uveitis and 20 patients with age-related cataract were included. METHODS: Aqueous samples were examined by real-time polymerase chain reaction (PCR) and by pathogen-specific analysis of intraocular antibody production (Goldmann-Witmer coefficient [GWC]) for herpes simplex virus (HSV), varicella zoster virus (VZV), cytomegalovirus (CMV), and the parasite Toxoplasma gondii. MAIN OUTCOME MEASURES: Results of aqueous analysis and any adverse effects of aqueous sampling. Correlations between the results of aqueous testing and clinical characteristics as well as the treatment of patients. RESULTS: Of 152 patients, 44 (29%) had positive results for at least one diagnostic assay (37/136 [28%] immunocompetent and 7/16 [44%] immunocompromised patients). None of the controls had positive results using PCR or GWC. A positive result was obtained predominantly in patients with focal chorioretinitis (37/87 [40%]) and in extensive retinitis (7/9 [78%]), whereas in multifocal chorioretinitis, neuroretinitis, and retinal vasculitis only a few samples demonstrated positive results (2/19, 1/29, and 0/10, respectively). Of 37 immunocompetent PU patients with positive results, 28 (76%) cases were caused by T. gondii, whereas viral infections were most common in immunocompromised patients (5/7 [71%]). In immunocompetent and toxoplasmosis PU patients, GWC was the most informative assay (34/37 [92%] and 28/30 [93%], respectively), in contrast to immunosuppressed patients (PCR positive in 5/7 and GWC positive in 4/7). Independent of the immune status of patients, positive PCR results were observed more frequently in viral infections than in toxoplasmosis (P<0.001). As a consequence of aqueous analysis, change of treatment was necessary in 36 patients (24%). None of the patients experienced complications during or after aqueous sampling. CONCLUSIONS: Despite the posterior location of inflammation, aqueous analyses with PCR and GWC for HSV, VZV, CMV, and T. gondii revealed an infectious cause in 29% of patients with PU.

Rate-difference method proved satisfactory in estimating the influenza burden in primary care visits.

OBJECTIVE: To compare different methods to estimate the disease burden of influenza, using influenza and respiratory syncytial virus-(RSV) associated primary care data as an example. STUDY DESIGN AND SETTING: In a retrospective study in the Netherlands over 1997-2003, primary care attended respiratory episodes and national viral surveillance data were used to compare the rate-difference method to other, more complex methods. RESULTS: The influenza-associated excess estimated by the different methods varied. The estimates provided by the rate-difference model lay well within this range. According to the rate-difference method, influenza-associated primary care consultations were present for all ages, including low-risk adults. The highest influenza-associated burden was demonstrated for children below the age of 5 years. The RSV-associated primary care burden was highest in the youngest age category and well above that associated with influenza. Significant RSV-associated excess was also recorded among adults, particularly in high-risk adults and the elderly. CONCLUSION: The straightforward rate-difference model seemed satisfactory to estimate the influenza-associated burden. Significant influenza-associated excess was demonstrated among persons not yet recommended for influenza vaccination in The Netherlands. The RSV-associated burden was highest for the youngest children, but also significant for adults.

Severe neonatal parechovirus infection and similarity with enterovirus infection.

BACKGROUND: Enteroviruses (EV) are an important cause of neonatal disease including hepatitis, meningoencephalitis, and myocarditis that can lead to death or severe long-term sequelae. Less is known about severe neonatal infection caused by the parechoviruses (PeV) of which type 1 (PeV1) and type 2 (PeV2) were previously known as echovirus 22 and echovirus 23. They belong to the same family of Picornaviridae as the EV. Of the PeV, so far only PeV3 has been associated in 2 recent reports with severe neonatal infection including involvement of central nervous system. METHODS: We compared the clinical signs, diagnosis, laboratory data, cerebral imaging, and neurodevelopmental outcome of 11 neonates with PeV infection with 21 infants with EV infection treated in our hospital between 1994 and 2006. The diagnosis of EV infection or PeV infection was confirmed by a positive EV and/or PeV real time-polymerase chain reaction on blood, cerebrospinal fluid, (CSF) or stool or a viral culture of stool, nasopharyngeal swab, and/or CSF. RESULTS: The 32 infants presented with sepsis-like illness and the most frequent signs were: fever, seizures, irritability, rash, and feeding problems. All patients received antibiotic treatment. Eleven of 21 infants infected with EV and 7 of 11 infants infected with PeV were full-term. Differentiation between the infants infected with EV and PeV on the basis of fever, irritability, rash, and seizures was not possible. Myocarditis was exclusively seen in 4 patients infected by EV. Eight of 11 patients with a PeV infection had meningoencephalitis of whom only 1 infant developed pleocytosis in the CSF. Serum C-reactive protein and CSF protein values were significantly higher in infants with EV infection than in those with PeV infection. Cerebral imaging of all infants with EV or PeV cerebral infection showed mild to severe white matter abnormalities. In 1 infant with EV infection and 3 infants with PeV infection, neurodevelopmental delay occurred. Mortality and long-term sequelae were mainly associated with myocarditis in the infants who were infected with EV (4 of 21). CONCLUSIONS: It is not possible to distinguish neonatal PeV from EV infection on the basis of clinical signs. Neonates with PeV or EV infection present with sepsis-like illness and the most frequent signs are fever, seizures, irritability, rash, and feeding problems.

Enhanced severity of virus associated lower respiratory tract disease in asthma patients may not be associated with delayed viral clearance and increased viral load in the upper respiratory tract.

BACKGROUND: Viral respiratory infections, particularly human rhinovirus (HRV) infections, are the most common cause of asthma exacerbation. HRV infections usually lead to more severe and longer duration of lower respiratory tract (LRT) symptoms in asthmatics than in otherwise healthy individuals. However, the exact mechanism by which viruses contribute to exacerbation of asthma is unknown. OBJECTIVES: The main objective of our study was to investigate the relationship of the enhanced severity of LRT symptoms to viral dynamics or cytokine responses in the upper respiratory tract (URT). STUDY DESIGN: Therefore, we conducted a longitudinal study in which asthmatics and healthy controls were followed during natural viral respiratory tract infections. RESULTS: Our study confirmed that viral respiratory tract infections caused more severe problems of the LRT in asthma patients as compared to healthy controls. However, for all subjects, the severity of LRT symptoms were not related to viral load or prolonged viral shedding in the URT. In addition, we did not detect differences in proinflammatory cytokines in the URT between asthmatics and controls. CONCLUSION: Persistence of the virus, as well as viral load in the URT, may not be associated with the induction and/or persistence of asthmatic symptoms.