Anne Pitkäranta

Detection of Rhinovirus, Respiratory Syncytial Virus, and Coronavirus Infections in Acute Otitis Media by Reverse Transcriptase Polymerase Chain Reaction

Objective. To determine the frequencies of human rhinovirus (HRV), respiratory syncytial virus (RSV), and coronavirus (HCV) infection in children with acute otitis media (AOM). Methods. Middle ear fluids (MEF) collected by tympanocentesis and nasopharyngeal aspirates (NPA) at the time of the AOM diagnosis were examined by reverse transcriptase polymerase chain reaction for HRV, RSV, and HCV RNA. Patients. Ninety-two children aged 3 months to 7 years during a 1-year period. Results. Virus RNA was detected in a total of 69 children (75%) and in 44 MEF samples (48%) and 57 NPA samples (62%) at the time of AOM diagnosis. HRV RNA was detected in both MEF and NPA in 18 (20%), in MEF alone in 4 (4%), and in NPA alone in 10 (11%). RSV was detected in both MEF and NPA in 12 (13%), in MEF alone in 5 (5%), and in NPA alone in 9 (10%). HCV RNA was detected in both MEF and NPA in 5 (5%), in MEF alone in 2 (2%), and in NPA alone in 9 (10%). Dual viral infections were detected in 5% of children. HRV and RSV were detected simultaneously in 2 MEF samples and in 2 NPA samples; RSV and HCV were detected in 1 NPA sample. Bacterial pathogens were detected in 56 (62%) MEF from 91 children. Viral RNA was detected in 20 (57%) MEF of 35 bacteria-negative and in 25 (45%) of 56 bacteria-positive MEF samples. No important differences in the risk of treatment failure, relapse, or occurrence of late secretory otitis media were noted between children with virus-positive and virus-negative MEF aspirates. Conclusion. These findings highlight the importance of common respiratory viruses, particularly HRV and RSV, in predisposing to and causing AOM in young children.

Polymerase chain reaction-based detection of rhinovirus, respiratory syncytial virus, and coronavirus in otitis media with effusion.

Abstract Objectives: To study the association of human rhinovirus (HRV), respiratory syncytial virus (RSV), and human coronavirus infections in children aged 6 months to 12 years with otitis media with effusion (OME). To determine how long HRV RNA can be detected after HRV infection. Methods: Middle ear effusion (MEE) samples collected at the time of tympanostomy tube placement from 100 children with OME were examined. Viral RNA was detected by reverse-transcriptase polymerase chain reaction. For HRV the results were compared with virus isolation in cell culture. In vitro studies of the persistence of HRV infectivity and RNA were conducted by combining ~105 median cell culture infectious doses of HRV with pooled MEE at 37°C and assaying serial samples for 12 weeks. Results: Virus RNA was detected in 30 children. HRV was detected by reverse-transcriptase polymerase chain reaction in 19 children with OME and by virus isolation in 5 children. RSV RNA was found in 8 and HCV in 3 children with OME. No dual viral infection was found. Bacterial pathogens were isolated from 35 MEE samples and were associated with viral RNA in 11 cases, most often with HRV (9 cases). Under in vitro conditions, HRV culture positivity declined rapidly (<2 days), but RNA was detectable for up to 8 weeks. Conclusions: These results suggest that virus infection, particularly HRV infection, either alone or concurrent with bacteria, is present in a larger percentage of children with OME than previously suspected. It remains to be determined how often the presence of viral RNA in MEE represents persistent RNA, ongoing viral replication, or recurrent infection. (J Pediatr 1998;133:390-4)

Slow initial β-lactam infusion and oral paracetamol to treat childhood bacterial meningitis: a randomised, controlled trial

BACKGROUND New antimicrobials or adjunctive treatments have not substantially reduced mortality from acute childhood bacterial meningitis. Paracetamol seems to have beneficial effects in bacteraemic adults and some experts recommend initial slow β-lactam infusion. We investigated whether these treatments had benefits in children with bacterial meningitis. METHODS We did a prospective, double-blind, single-centre study with a two-by-two factorial design in Luanda, Angola. 723 participants aged 2 months to 13 years were randomly assigned two 12 h intravenous infusions, without loading doses, of 125 mg/kg bodyweight cefotaxime (total dose 250 mg/kg) given over 24 h, or 250 mg/kg bodyweight cefotaxime given as four boluses, one every 6 h over 24 h. Patients also received oral paracetamol at an initial dose of 30 mg/kg then 20 mg/kg every 6 h for 48 h or placebo. Two primary endpoints, death or severe neurological sequelae and deafness, were analysed by intention to treat. The study was registered as ISRCTN62824827. FINDINGS 183 patients were assigned cefotaxime infusion plus paracetamol and 180 patients to each of the other three treatment groups. Causative agents were identified in 63% of cases and were mostly Haemophilus influenzae type b, Streptococcus pneumoniae, or Neisseria meningitidis. Death or severe neurological sequelae were seen in 340 (47%) of 723 children and deafness in 45 (12%) of 374 tested, both distributed similarly across treatment groups. In a predefined subgroup analysis of death or any sequelae, by causative agent, a benefit was seen in favour of infusion over bolus in children with pneumococcal meningitis (infusion plus placebo, odds ratio 0·18, 95% CI 0·03-0·90, p=0·04). A similar effect was seen for children receiving cefotaxime infusion plus paracetamol, but the difference was not significant (OR 0·22, 95% CI 0·04-1·09, p=0·06). A post-hoc analysis suggested that cefotaxime infusion plus paracetamol lowered mortality at least during the first 3 days, irrespective of cause. INTERPRETATION Although no tested regimen improved the final outcomes of these very ill children, studies of longer courses of β-lactam infusion plus paracetamol seem warranted. FUNDING The Päivikki and Sakari Sohlberg, the Sigrid Jusélius, and the Paediatric Research Foundations, and the daily newspaper Helsingin Sanomat.

Milk containing probiotic Lactobacillus rhamnosus GG and respiratory illness in children: a randomized, double-blind, placebo-controlled trial

Background/Objectives:To determine whether long-term daily consumption of milk containing probiotic Lactobacillus rhamnosus GG (GG) decreases respiratory illness in children.Subjects/Methods:A randomized, double-blind, placebo-controlled trial was conducted with 523 children aged 2–6 years attending day care centers in Finland. Subjects received either normal milk or the same milk with GG on three daily meals for 28 weeks. Daily recording of childrens’ symptoms was done by parents. Primary outcome data from 501 subjects were available for analysis, and data from 128 subjects were analyzed as completed cases in terms of recovery of GG in fecal samples.Results:Number of days with at least one respiratory symptom in all subjects was 5.03/month (95% confidence interval (CI): 4.92–5.15) in the GG group and 5.17/month (95% CI: 5.05–5.29) in the placebo group incidence rate ratio (IRR) 0.97; 95% CI: 0.94–1.00; P=0.098). In the completed cases, the figures were 4.71 days/month (95% CI: 4.52–4.90) in the GG group and 5.67 days/month (95% CI: 5.40–5.94) in the placebo group (IRR 0.83; 95% CI: 0.78–0.88; P<0.001).Conclusions:Consumption of GG reduced the occurence of respiratory illness in children attending day care centers in the completed cases subgroup, but not in the total population. Thus, future clinical trials are warranted to clarify the association between fecal recovery of a probiotic and the symptom prevalence.

Rhinovirus RNA in the Maxillary Sinus Epithelium of Adult Patients with Acute Sinusitis

We used in situ hybridization for the detection of rhinovirus in maxillary sinus biopsy specimens obtained from 14 adult patients with acute sinusitis. In 7 specimens, rhinovirus RNA could be demonstrated in the maxillary sinus epithelium, thereby confirming the etiology of rhinovirus and the clinical suspicion of acute sinusitis.

Sleep problems and daytime tiredness in Finnish preschool-aged children-a community survey.

BACKGROUND Sleep is important to the well-being and development of children. Specially, small children are vulnerable to the effects of inadequate sleep. However, not much is known about the frequency of all types of sleep problems and daytime tiredness in preschool-aged children. OBJECTIVE To evaluate the prevalence of a wide spectrum of sleep problems, daytime tiredness and associations between these in 3- to 6-year-old Finnish children. METHODS A population-based study where parents of 3- to 6-year-old children (n= 904) living in Helsinki filled in the Sleep Disturbance Scale for Children (SDSC). RESULTS Of the children, 45% had at least one sleep-related problem occurring at least three times a week: 14.1% were unwilling to go to bed, 10.2% had difficulties in falling asleep, 10.2% had bruxism, 6.4% sleep talking, 2.1% sleep terrors, 8.2% had sleep-related breathing problem, 11.2% had excessive sweating while falling asleep and 12.9% excessive sweating during sleep. Age and gender were related to phenotype of the sleeping problems. In multiple regression analysis, the difficulties in initiating and maintaining sleep were most strongly associated with tiredness in the morning and during the day. CONCLUSIONS Different types of sleep problems are frequent in preschool-aged children. Poor sleep quality is associated with morning and daytime tiredness. In screening for sleep problems in children, attention should be paid not only to sleep amount but also to sleep quality.

Lowered yields of virus-induced interferon production in leukocyte cultures and risk of recurrent respiratory infections in children

Abstract Objective: To study the correlation between the yield of virus-induced interferon (IFN) production in leukocyte cultures and the risk of recurrent respiratory infections. Methods: A sample of 71 consecutive children enrolled in the Finnish Otitis Media Cohort Study were selected. Children suffering from frequently recurring respiratory infections (FRRIs) were defined as the highest quintile of the entire cohort of 329 children, as regards the number of upper respiratory infections (URIs) and/or episodes of acute otitis media (AOM) during the follow-up period from 2 to 24 months. Results: In the sample of 71 children, there were 18 children with FRRI (≥9 URI and/or ≥4 AOM). Leukocyte cultures, prepared from blood drawn from these 18 children at 6 months of age, produced lower yields of IFN than those of the remaining 53 children, when stimulated with adenovirus (P<0.001), coronavirus (P<0.001) or rhinovirus (P=0.002). The difference in IFN yields was even greater (P<0.001 with all three viruses) if the comparison was made between children with FRRI and those with no or maximally one URI during the follow-up period. When the IFN production capacity induced by rhinovirus was measured at the age of 24 months, a statistically significant difference between the children with FRRI and the others was also seen (P=0.002). Influenza A virus-induced IFN production capacity did not differ between the groups at either age (P=0.209). Conclusions: Lowered IFN responses in children suffering from recurrent URIs and/or AOM may, in a subgroup of the children, be due to a genetic property of the child. However, because of the great interindividual variations, we cannot use the IFN production capacity as such for prediction of forthcoming respiratory infections and/or otitis media.

Detection of rhinovirus RNA in middle turbinate of patients with common colds by in situ hybridization.

Human rhinovirus 14 RNA was determined by in situ hybridization from middle turbinate biopsies in 32 patients with diagnosed common colds and in five control individuals. Twenty‐two (69%) biopsies from common colds patients but none of the five control biopsies showed reactivity for human rhinovirus 14 antisense probe. The signal was detected both in the respiratory epithelium and in mucosal inflammatory cells. In situ hybridization of the middle turbinate tissue yielded more positive results than RT‐PCR (47%) or virus culture (34%) assayed from nasopharyngeal aspirates, but no statistical significant differences were observed (P = 0.265, P = 0.425, respectively). The results indicated that in situ hybridization procedure was slightly more sensitive than PCR assays and classical culture for the detection of human rhinovirus infection of upper respiratory tract. However, in situ hybridization procedure appeared to be an interesting methodology to investigate the physiopathology of respiratory tract infection by rhinoviruses. J. Med. Virol. 70: 319–323, 2003.

Prednisolone in Bell's Palsy Related to Treatment Start and Age.

Objective: To evaluate if treatment start and age are related to the outcome in Bells palsy patients treated with prednisolone. Study Design: Prospective, randomized, double-blind, placebo-controlled, multicenter trial. Setting: Sixteen otorhinolaryngologic centers in Sweden and 1 in Finland. Patients Data were collected from the Scandinavian Bells palsy study. A total of 829 patients were treated within 72 hours of onset of palsy. Follow-up was 12 months. Intervention: Patients were randomly assigned to treatment with placebo plus placebo (n = 206), prednisolone plus placebo (n = 210), valacyclovir plus placebo (n = 207), or prednisolone plus valacyclovir (n = 206). Main Outcome Measures: Facial function was assessed with the Sunnybrook grading system, and complete recovery was defined as Sunnybrook = 100. Time from onset of palsy to treatment start was registered. Results: Patients treated with prednisolone within 24 hours and 25 to 48 hours had significantly higher complete recovery rates, 66% (103/156) and 76% (128/168), than patients given no prednisolone, 51% (77/152) and 58% (102/177) (p = 0.008 and p = 0.0003, respectively). For patients treated within 49 to 72 hours of palsy onset, there were no significant differences. Patients aged 40 years or older had significantly higher complete recovery rates if treated with prednisolone, whereas patients aged younger than 40 years did not differ with respect to prednisolone treatment. However, synkinesis was significantly less in patients younger than 40 years given prednisolone (p = 0.002). Conclusion: Treatment with prednisolone within 48 hours of onset of palsy resulted in significantly higher complete recovery rates and less synkinesis compared with no prednisolone.

Clinical features, health-related quality of life, and adult voice in juvenile-onset recurrent respiratory papillomatosis†

To determine clinical features, health‐related quality of life, and adult voice in patients with a history of juvenile‐onset recurrent respiratory papillomatosis (JORRP).