Acute otitis media in children

Jacques CherpillodEar, Nose and Throat Department, Childrens’ University Hospital, Lausanne, SwitzerlandDate of preparation: 6th March 2011Conflict of interest: None declaredClinical question: What is the best treatment for acute otitis media in children?Results: Watchful waiting, followed by amoxicillin treatment, if necessary, is the best first-line treatment for acute otitis media in children aged six months or older.Keywords: acute otitis media, antibiotics, watchful waiti

Concentrations of azithromycin in tonsillar and/or adenoid tissue from paediatric patients

Azithromycin levels in tonsillar and/or adenoid tissue were determined in children (1.6-7.5 years old) who were scheduled for surgical removal of their tonsils and/or adenoids. The children received azithromycin oral suspension lOmg/kg once daily for 3 days. Tissue samples were obtained during surgery 1 (n = 4), 2 (n = 5), 4 (n = 6), or 8 (n = 5) days after the last dose of azithromycin. Serum samples were also obtained from four children in each of these groups at the time of surgery. Mean tissue concentrations of azithromycin were 10.33 ± 3.01, 7.21 ± 4.04, 9.30 ± 3.74 and 1.49 ± 0.48 mg/kg, respectively, 1, 2, 4 and 8 days after the last dose. At the corresponding times, serum concentrations were markedly lower: 47.25 ± 19 19, 14.00 ± 8.45, 8.00 ± 2.16 and <4 μg/L, respectively. The mean tissue:serum concentration ratios were, 227 ± 54, 547 ± 184 and 956 ± 355, respectively, 1, 2 and 4 days after treatment. No adverse events attributable to azithromycin were observed in any of the 23 children who had received at least one dose of azithromycin. The study shows that levels of azithromycin in tonsillar and adenoid tissue were consistently higher than in serum and remained elevated up to 8 days after the end of dosing, supporting the use of a short-course (3-day), once-daily regimen of azithromycin in the treatment of upper respiratory tract infection

Mechanism of reduction of virus release and cell-cell fusion in persistent canine distemper virus infection

Canine distemper virus (CDV), a mobillivirus related to measles virus causes a chronic progressive demyelinating disease, associated with persistence of the virus in the central nervous system (CNS). CNS persistence of morbilliviruses has been associated with cell-to-cell spread, thereby limiting immune detection. The mechanism of cell-to-cell spread remains uncertain. In the present study we studied viral spread comparing a cytolytic (non-persistent) and a persistent CDV strain in cell cultures. Cytolytic CDV spread in a compact concentric manner with extensive cell fusion and destruction of the monolayer. Persistent CDV exhibited a heterogeneous cell-to-cell pattern of spread without cell fusion and 100-fold reduction of infectious viral titers in supernatants as compared to the cytolytic strain. Ultrastructurally, low infectious titers correlated with limited budding of persistent CDV as compared to the cytolytic strain, which shed large numbers of viral particles. The pattern of heterogeneous cell-to-cell viral spread can be explained by low production of infectious viral particles in only few areas of the cell membrane. In this way persistent CDV only spreads to a small proportion of the cells surrounding an infected one. Our studies suggest that both cell-to-cell spread and limited production of infectious virus are related to reduced expression of fusogenic complexes in the cell membrane. Such complexes consist of a synergistic configuration of the attachment (H) and fusion (F) proteins on the cell surface. F und H proteins exhibited a marked degree of colocalization in cytolytic CDV infection but not in persistent CDV as seen by confocal laser microscopy. In addition, analysis of CDV F protein expression using vaccinia constructs of both strains revealed an additional large fraction of uncleaved fusion protein in the persistent strain. This suggests that the paucity of active fusion complexes is due to restricted intracellular processing of the viral fusion protei

Concentrations of azithromycin in tonsilar and/or adenoid tissue from paediatric patients.

Azithromycin levels in tonsillar and/or adenoid tissue were determined in children (1.6-7.5 years old) who were scheduled for surgical removal of their tonsils and/or adenoids. The children received azithromycin oral suspension 10 mg/kg once daily for 3 days. Tissue samples were obtained during surgery 1 (n = 4), 2 (n = 5), 4 (n = 6), or 8 (n = 5) days after the last dose of azithromycin. Serum samples were also obtained from four children in each of these groups at the time of surgery. Mean tissue concentrations of azithromycin were 10.33 +/- 3.01, 7.21 +/- 4.04, 9.30 +/- 3.74 and 1.49 +/- 0.48 mg/kg, respectively, 1, 2, 4 and 8 days after the last dose. At the corresponding times, serum concentrations were markedly lower: 47.25 +/- 19. 19, 14.00 +/- 8.45, 8.00 +/- 2.16 and &lt; 4 micrograms/L, respectively. The mean tissue:serum concentration ratios were, 227 +/- 54, 547 +/- 184 and 956 +/- 355, respectively, 1, 2 and 4 days after treatment. No adverse events attributable to azithromycin were observed in any of the 23 children who had received at least one dose of azithromycin. The study shows that levels of azithromycin in tonsillar and adenoid tissue were consistently higher than in serum and remained elevated up to 8 days after the end of dosing, supporting the use of a short-course (3-day), once-daily regimen of azithromycin in the treatment of upper respiratory tract infections

Predictive value of clinical and laboratory features for the main febrile diseases in children living in Tanzania: A prospective observational study.

To construct evidence-based guidelines for management of febrile illness, it is essential to identify clinical predictors for the main causes of fever, either to diagnose the disease when no laboratory test is available or to better target testing when a test is available. The objective was to investigate clinical predictors of several diseases in a cohort of febrile children attending outpatient clinics in Tanzania, whose diagnoses have been established after extensive clinical and laboratory workup. From April to December 2008, 1005 consecutive children aged 2 months to 10 years with temperature ≥38°C attending two outpatient clinics in Dar es Salaam were included. Demographic characteristics, symptoms and signs, comorbidities, full blood count and liver enzyme level were investigated by bi- and multi-variate analyses (Chan, et al., 2008). To evaluate accuracy of combined predictors to construct algorithms, classification and regression tree (CART) analyses were also performed. 62 variables were studied. Between 4 and 15 significant predictors to rule in (aLR+&gt;1) or rule out (aLR+&lt;1) the disease were found in the multivariate analysis for the 7 more frequent outcomes. For malaria, the strongest predictor was temperature ≥40°C (aLR+8.4, 95%CI 4.7-15), for typhoid abdominal tenderness (5.9,2.5-11), for urinary tract infection (UTI) age ≥3 years (0.20,0-0.50), for radiological pneumonia abnormal chest auscultation (4.3,2.8-6.1), for acute HHV6 infection dehydration (0.18,0-0.75), for bacterial disease (any type) chest indrawing (19,8.2-60) and for viral disease (any type) jaundice (0.28,0.16-0.41). Other clinically relevant and easy to assess predictors were also found: malaria could be ruled in by recent travel, typhoid by jaundice, radiological pneumonia by very fast breathing and UTI by fever duration of ≥4 days. The CART model for malaria included temperature, travel, jaundice and hepatomegaly (sensitivity 80%, specificity 64%); typhoid: age ≥2 years, jaundice, abdominal tenderness and adenopathy (46%,93%); UTI: age &lt;2 years, temperature ≥40°C, low weight and pale nails (20%,96%); radiological pneumonia: very fast breathing, chest indrawing and leukocytosis (38%,97%); acute HHV6 infection: less than 2 years old, (no) dehydration, (no) jaundice and (no) rash (86%,51%); bacterial disease: chest indrawing, chronic condition, temperature ≥39.7°c and fever duration &gt;3 days (45%,83%); viral disease: runny nose, cough and age &lt;2 years (68%,76%). A better understanding of the relative performance of these predictors might be of great help for clinicians to be able to better decide when to test, treat, refer or simply observe a sick child, in order to decrease morbidity and mortality, but also to avoid unnecessary antimicrobial prescription. These predictors have been used to construct a new algorithm for the management of childhood illnesses called ALMANACH

Gentamicin Exposure and Sensorineural Hearing Loss in Preterm Infants.

To evaluate the impact of gentamicin exposure on sensorineural hearing loss (SNHL) in very low birth weight (VLBW) infants. Exposure to gentamicin was determined in infants born between 1993 and 2010 at a gestational age &lt; 32 weeks and/or with a birthweight &lt; 1500 g, who presented with SNHL during the first 5 years of life. For each case, we selected two controls matched for gender, gestational age, birthweight, and year of birth. We identified 25 infants affected by SNHL, leading to an incidence of SNHL of 1.58% in our population of VLBW infants. The proportion of infants treated with gentamicin was 76% in the study group and 70% in controls (p = 0.78). The total cumulated dose of gentamicin administered did not differ between the study group (median 10.2 mg/kg, Q1-Q3 1.6-13.2) and the control group (median 7.9 mg/kg, Q1-Q3 0-12.8, p = 0.47). The median duration of gentamicin treatment was 3 days both in the study group and the control group (p = 0.58). Maximum predicted trough serum levels of gentamicin, cumulative area under the curve and gentamicin clearance were not different between cases and controls. The impact of gentamicin on SNHL can be minimized with treatments of short duration, monitoring of blood levels and dose adjustment

Beyond malaria--causes of fever in outpatient Tanzanian children.

BACKGROUND: As the incidence of malaria diminishes, a better understanding of nonmalarial fever is important for effective management of illness in children. In this study, we explored the spectrum of causes of fever in African children. METHODS: We recruited children younger than 10 years of age with a temperature of 38°C or higher at two outpatient clinics--one rural and one urban--in Tanzania. Medical histories were obtained and clinical examinations conducted by means of systematic procedures. Blood and nasopharyngeal specimens were collected to perform rapid diagnostic tests, serologic tests, culture, and molecular tests for potential pathogens causing acute fever. Final diagnoses were determined with the use of algorithms and a set of prespecified criteria. RESULTS: Analyses of data derived from clinical presentation and from 25,743 laboratory investigations yielded 1232 diagnoses. Of 1005 children (22.6% of whom had multiple diagnoses), 62.2% had an acute respiratory infection; 5.0% of these infections were radiologically confirmed pneumonia. A systemic bacterial, viral, or parasitic infection other than malaria or typhoid fever was found in 13.3% of children, nasopharyngeal viral infection (without respiratory symptoms or signs) in 11.9%, malaria in 10.5%, gastroenteritis in 10.3%, urinary tract infection in 5.9%, typhoid fever in 3.7%, skin or mucosal infection in 1.5%, and meningitis in 0.2%. The cause of fever was undetermined in 3.2% of the children. A total of 70.5% of the children had viral disease, 22.0% had bacterial disease, and 10.9% had parasitic disease. CONCLUSIONS: These results provide a description of the numerous causes of fever in African children in two representative settings. Evidence of a viral process was found more commonly than evidence of a bacterial or parasitic process. (Funded by the Swiss National Science Foundation and others.)