Burden of Disease in Hospitalized RSV-positive Children in Germany

Abstract

Background: In spite of a large amount of data from other countries, those on the burden of disease attributed to respiratory syncytial virus (RSV) in Germany are lacking and are urgently needed. Method: In a population-based cross-sectional study from July 1996 to June 1999 150 children from birth to 16 years of age hospitalized in Kiel and tested positive for RSV by polymerase chain reaction were investigated. Stepwise linear and logistic regression models were applied to predict a bacterial co-infection as well as the duration of hospitalization. Results: Pneumonia (54 %) and wheezing bronchitis (including bronchiolitis, 27 %) were the predominating diagnoses; 25 % had an underlying condition. Four patients needed nasal continuous airway pressure and one intermittent mandatory ventilation; none died. According to the surrogate markers CRP and immature neutrophil fraction, 20 % to 30 % were suspected to have a bacterial co-infection on admission; antibiotics were prescribed in 65 % of the patients. The average duration of hospitalization was 9 days and was best predicted by young age, the presence of an underlying condition, intercostal retractions and high CRP on admission. Conclusions: Bacterial co-infection is the major confounder in burden of disease analyses in RSV. The decision not to administer antibiotics to children hospitalized with RSV can be risky, particularly when there is considerable diagnostic uncertainty. Within the realm of current clinical practice, complications and deaths related to RSV are rare in Germany.

Zusammenfassung

Hintergrund: Trotz einer großen Datenmenge zur klinischen Bedeutung der RSV-Infektion in anderen Ländern ist diesbezüglich die Datenlage in Deutschland noch unzureichend. Methode: In einer populationsbezogenen Querschnittsstudie von Juli 1996 bis Juni 1999 wurden 150 Kinder im Alter von 0 - 16 Jahren eingeschlossen, die in Kiel stationär behandelt wurden und mittels Polymerase-Ketten-Reaktion positiv für RSV getestet wurden. Schrittweise lineare und logistische Regressionsmodelle wurden verwendet, um eine bakterielle Koinfektion vorherzusagen und die Einflussgrößen auf die stationäre Behandlungsdauer erkennen zu können. Ergebnisse: Pneumonien (54 %) und obstruktive Bronchitiden (einschließlich Bronchiolitis, 27 %) waren die häufigsten Diagnosen; 25 % der Patienten hatten eine chronische Grundkrankheit. Vier bedurften einer nasalen CPAP- und ein Patient einer IMV-Beatmung; kein Patient verstarb. Entsprechend den Surrogatmarker C-reaktives Protein und unreife neutrophile Granulozyten hätten 20 - 30 % eine bakterielle Koinfektion zum Zeitpunkt der stationären Aufnahme gehabt; 65 % erhielten Antibiotika. Die durchschnittliche stationäre Behandlungsdauer betrug 9 Tage und wurde am stärksten durch das junge Alter des Patienten, dem Vorhandensein einer Grundkrankheit, interkostalen Einziehungen und einem hohen C-reaktiven Protein erklärt. Schlussfolgerungen: Bakterielle Koinfektionen sind die wichtigste Verzerrvariable bei der Analyse der Bedeutung von RSV-Infektionen. Die Entscheidung stationär wegen RSV zu behandelnden Kindern kein Antibiotikum zu geben, kann gefährlich sein, insbesondere in Anbetracht der diagnostischen Unsicherheit für bakterielle tiefe Atemwegsinfektionen bei Kindern. Beim derzeitigen klinischen Vorgehen sind Komplikationen und Todesfälle in Verbindung mit einer RSV-Infektion in Deutschland selten.

Acute respiratory tract infection - C-reactive protein - Disease burden - Infiltrates - RSV

Akute Atemwegsinfektion - C-reaktives Protein - Infiltrate - RSV - Stationär

Literatur

• 1 Weigl J AI, Puppe W, Schmitt H-J. The incidence of respiratory syncytial virus-associated hospitalizations in Germany.  Eur J Clin Microbiol Infect Dis. 2001;  20 452-459
• 2 Karron R A, Singleton R J, Bulkow L, Parkinson A, Kruse D, DeSmet I. et al . Severe respiratory syncytial virus disease in Alaska native children.  Clin Infect Dis. 1999;  180 41-49
• 3 Kristensen K, Dahm T, Frederiksen P S, Ibsen J, Iyore E, Jensen A M. et al . Epidemiology of respiratory syncytial cirus infection requiring hospitalization in East Denmark.  Pediatr Infect Dis J. 1998;  17 996-1000
• 4 Gardner P S. Respiratory syncytial virus infections.  Postgraduate Med J. 1973;  49 788-791
• 5 Martin A J, Gardner P S, McQuillin J. Epidemiology of respiratory viral infection among paediatric inpatients over a six-year period in North-East England.  Lancet. 1978;  2 1035-1038
• 6 Eriksson M, Forsgren M, Sjöberg S, von Sydow M, Wolontis S. Respiratory syncytial virus infection in young hospitalized children.  Acta Paediatr Scand. 1983;  72 47-51
• 7 Wickman M, Farahmand B Y, Persson P-G, Pershagen G. Hospitalization for lower respiratory disease during 20 yrs among under 5 yr old children in Stockholm County: a population based survey.  Eur Respir J. 1998;  11 366-370
• 8 Ørstavik I, Carlsen K-H, Halvorsen K. Respiratory Syncytial Virus Infections in Oslo 1972 - 1978. I. Virological and epidemiological studies.  Acta Paediatr Scand. 1980;  69 717-722
• 9 Ministerium für Arbeit, Gesundheit und Soziales des Landes Schleswig-Holstein . Zur Gesundheitslage der Kinder in Schleswig-Holstein - Daten, Einschätzungen, Fragen. Kiel; b + c computergraphic 1997: 3-4
• 10 Gröndahl B, Puppe W, Hoppe A, Kühne I, Weigl J AI, Schmitt H-J. Rapid identification of nine microorganisms causing acute respiratory tract infections by single-tube multiplex reverse transcription-PCR: Feasibility study.  J Clin Microbiol. 1999;  37 1-7
• 11 Weigl J AI, Puppe W, Gröndahl B, Schmitt H-J. Epidemiological investigation of nine respiratory pathogens in hospitalized children in Germany using multiplex reverse-transcriptase polymerase chain reaction.  Eur J Clin Microbiol Infect Dis. 2000;  19 336-343
• 12 Falla T J, Crook D WM, Brophy L N, Maskell D, Kroll J S, Moxon E R. PCR for capsular typing of Haemophilus influenzae.  J Clin Microbiol. 1994;  32 2382-2386
• 13 Isaacs D. Is bronchiolitis an obsolete term?.  Curr Opin Pediatr. 1998;  10 1-3
• 14 Hall C B. Respiratory Syncytial Virus. In: Mandell GL, Bennett JE, Dolin R (eds) Principles and Practice of Infectious Diseases. 5th ed. Philadelphia; Livingstone 2000 2: 2084-2111
• 15 Behrendt C E, Decker M D, Burch D J, Watson P H. for the International RSV Study Group . International variation in the management of infants hospitalized with respiratory syncytial virus.  Eur J Pediatr. 1998;  157 215-220
• 16 Brandenburg A H, Jeannet P-Y, von Steensel-Moll H A, Ott A, Rothbarth P H, Wunderli W. et al . Local variability in respiratory syncytial virus disease severity.  Arch Dis Child. 1997;  77 410-414
• 17 Carlsen K-H, Ørstavik I. Respiratory syncytial virus infections in Oslo 1972 - 1978. II. Clinical and laboratory studies.  Acta Paediatr Scand. 1980;  69 723-729
• 18 Wang E EL, Law B, Stephens D. Pediatric investigators collaborative network on infections in Canada (PICNIC) prospective study of risk factors and outcomes in patients hospitalized with respiratory syncytial viral lower respiratory tract infection.  J Pediatr. 1995;  126 212-219
• 19 Meert K, Heidemann S, Abella B, Sarnaik A. Does prematurity alter the course of respiratory syncytial virus infection?.  Crit Care Med. 1990;  18 1357-1359
• 20 Ärztekammer Schleswig-Holstein . Perinatalerhebung 1997. Bad Segeberg; 1997: 13
• 21 Cunningham C K, McMillan J A, Gross S J. Rehospitalization for respiratory illness in infants of less than 32 weeks' gestation.  Pediatrics. 1991;  88 527-532
• 22 Tammela O T. First-year infections after initial hospitalization in low birth weight infants with and without bronchopulmonary dysplasia.  Scand J Infect Dis. 1992;  24 515-524
• 23 Hall C B, Douglas R G, Geiman J M, Messner M K. Nosocomial respiratory syncytial virus infections.  New Engl J Med. 1975;  293 1343-1346
• 24 Moler F W, Khan A S, Meliones J N, Custer J R, Palmisano J, Shope T C. Respiratory syncytial virus morbidity and mortality estimates in congenital heart disease patients: A recent experience.  Crit Care Med. 1992;  20 1406-1413
• 25 MacDonald N E, Hall C B, Suffin S C, Alexson C, Harris P J, Manning J A. Respiratory syncytial viral infection in infants with congenital heart disease.  New Engl J Med. 1982;  307 397-400
• 26 Berkovich S, Kibrick S. Exanthem associated with respiratory syncytial virus infection.  J Pediatr. 1964;  65 368-370
• 27 Isaacs D. Problems in determining the etiology of community-aquired childhood pneumonia.  Pediatr Infect Dis J. 1989;  8 143-148
• 28 Korppi M, Heiskanen-Kosma T, Leinonen M. White blood cells, C-reactive protein and erythrocyte sedimentation rate in pneumococcal pneumonia in children.  Eur Respir J. 1997;  10 1125-1129
• 29 Heiskanen-Kosma T, Korppi M. Serum C-reactive protein cannot differentiate bacterial and viral aetiology of community-acquired pneumonia in children in primary healthcare settings.  Scand J Infect Dis. 2000;  32 399-402
• 30 Saijo M, Ishii T, Kokubo M, Murono K, Takimoto M, Fujita K. White blood cell count, C-reactive protein and erythrocyte sedimentation rate in respiratory syncytial virus infection of the lower respiratory tract.  Acta Paediatr Jap. 1996;  38 596-600
• 31 Hall C B, Powell K R, Schnabel K C, Gala C L, Pincus P. Risk of secondary infection in infants hospitalized with respiratory syncytial viral infection.  J Pediatr. 1988;  113 266-271
• 32 Heiskanen-Kosma T, Korppi M, Jokinen C, Kurki S, Heiskanen L, Juvonen H. et al . Etiology of childhood pneumonia: serologic results of a prospective, population-based study.  Pediatr Infect Dis J. 1998;  17 986-991
• 33 Juven T, Mertsola J, Waris M, Leinonen M, Meurman O, Roivainen M. et al . Etiology of community acquired pneumonia in 254 hospitalized children.  Pediatr Infect Dis J. 2000;  19 293-298
• 34 Leinonen M. Serological diagnosis of pneumococcal pneumonia - will it ever become clinical reality.  Sem respir Infect. 1994;  9 189-191
• 35 Lukic-Grlic A, Bace A, Lokar-Kolbas R, Loffeler-Badzek D, Drazenovic V, Bozikov J. et al . Clinical and epidemiological aspects of respiratory syncytial virus lower respiratory tract infections.  Eur J Epidemiol. 1999;  15 361-365
• 36 Berner R, Schumacher R F, Brandis M, Forster J. Colonization and infection with Moraxella catarrhalis in childhood.  Eur J Clin Microbiol Infect Dis. 1996;  15 506-509
• 37 The Impact-RSV study group . Palivizumab, a humanized respiratory syncytial virus monoclonal antibody, reduces hospitalization from respiratory syncytial virus infection in high-risk infants.  Pediatrics. 1998;  102 531-537
• 38 The PREVENT study group . Reduction of respiratory syncytial virus hospitalization among premature infants with bronchopulmonary dysplasia using respiratory syncytial virus immune globulin prophylaxis.  Pediatrics. 1997;  991 93-99