Febrile illness in high-risk children: a prospective, international observational study
van der Velden FJS., de Vries G., Martin A., Lim E., von Both U., Kolberg L., Carrol ED., Khanijau A., Herberg JA., De T., Galassini R., Kuijpers TW., Martinón-Torres F., Rivero-Calle I., Vermont CL., Hagedoorn NN., Pokorn M., Pollard AJ., Schlapbach LJ., Tsolia M., Elefhteriou I., Yeung S., Zavadska D., Fink C., Voice M., Zenz W., Kohlmaier B., Agyeman PKA., Usuf E., Secka F., de Groot R., Levin M., van der Flier M., Emonts M., Levin M., Cunnington A., De T., Herberg J., Kaforou M., Wright V., Baumard L., Bellos E., D’Souza G., Galassini R., Habgood-Coote D., Hamilton S., Hoggart C., Hourmat S., Jackson H., Maconochie I., Menikou S., Lin N., Nichols S., Nijman R., Powell O., Pena Paz I., Shah P., Shen C-F., Vito O., Wilson C., Abdulla A., Ali L., Darnell S., Jorgensen R., Mustafa S., Persand S., Stevens MM., Kim N., Kim E., Fidler K., Dudley J., Richmond V., Tavliavini E., Shen C-F., Liu C-C., Wang S-M., Martinón-Torres F., Salas A., Álvez González F., Balo Farto C., Barral-Arca R., Barreiro Castro M., Bello X., García MB., Carnota S., Cebey-López M., Curras-Tuala MJ., Durán Suárez C., García Vicente L., Gómez-Carballa A., Gómez Rial J., Leboráns Iglesias P., Martinón-Torres F., Martinón-Torres N., Martinón Sánchez JM., Mosquera Pérez B., Pardo-Seco J., Rodríguez LP., Pischedda S., Vázquez SR., Rivero Calle I., Rodríguez-Tenreiro C., Redondo-Collazo L., Sadiki Ora M., Salas A., Serén Fernández S., Serén Trasorras C., Vilas Iglesias M., Zavadska D., Balode A., Bārzdiņa A., Deksne D., Gardovska D., Grāvele D., Grope I., Meiere A., Nokalna I., Pavāre J., Pučuka Z., Selecka K., Rudzāte A., Svile D., Urbāne UN., Usuf E., Bojang K., Zaman SMA., Secka F., Anderson S., RocaIsatou Sarr A., Saidykhan M., Darboe S., Ceesay S., D’alessandro U., Moll HA., Vermont CL., Borensztajn DM., Hagedoorn NN., Tan C., Zachariasse J., Dik W., Agyeman PKA., Berger C., Giannoni E., Stocker M., Posfay-Barbe KM., Heininger U., Bernhard-Stirnemann S., Niederer-Loher A., Kahlert CR., Natalucci G., Relly C., Riedel T., Aebi C., Schlapbach LJ., Carrol ED., Cocklin E., Jennings R., Johnston J., Khanijau A., Leigh S., Lewis-Burke N., Newall K., Romaine S., Tsolia M., Eleftheriou I., Tambouratzi M., Marmarinos A., Xagorari M., Syggelou K., Fink C., Voice M., Calvo-Bado L., Zenz W., Kohlmaier B., Schweintzger NA., Sagmeister MG., Kohlfürst DS., Zurl C., Binder A., Hösele S., Leitner M., Pölz L., Rajic G., Bauchinger S., Baumgart H., Benesch M., Ceolotto A., Eber E., Gallistl S., Gores G., Haidl H., Hauer A., Hude C., Keldorfer M., Krenn L., Pilch H., Pfleger A., Pfurtscheller K., Nordberg G., Niedrist T., Rödl S., Skrabl-Baumgartner A., Sperl M., Stampfer L., Strenger V., Till H., Trobisch A., Löffler S., Yeung S., Dewez JE., Hibberd M., Bath D., Miners A., Nijman R., Fitchett E., de Groot R., van der Flier M., de Jonge MI., van Aerde K., Alkema W., van den Broek B., Gloerich J., van Gool AJ., Henriet S., Huijnen M., Philipsen R., Willems E., Gerrits GPJM., van Leur M., Heidema J., de Haan L., Miedema CJ., Neeleman C., Obihara CC., Tramper-Stranders GA., Pollard AJ., Kandasamy R., Paulus S., Carter MJ., O’Connor D., Bibi S., Kelly DF., Gurung M., Thorson S., Ansari I., Murdoch DR., Shrestha S., Oliver Z., Emonts M., Lim E., Valentine L., Allen K., Bell K., Chan A., Crulley S., Devine K., Fabian D., King S., McAlinden P., McDonald S., McDonnell A., Pickering A., Thomson E., Wood A., Wallia D., Woodsford P., Baxter F., Bell A., Rhodes M., Agbeko R., Mackerness C., Baas B., Kloosterhuis L., Oosthoek W., Arif T., Bennet J., Collings K., van der Giessen I., Martin A., Rashid A., Rowlands E., de Vries G., van der Velden F., Soon J., Valentine L., Martin M., Mistry R., von Both U., Kolberg L., Zwerenz M., Buschbeck J., Bidlingmaier C., Binder V., Danhauser K., Haas N., Griese M., Feuchtinger T., Keil J., Kappler M., Lurz E., Muench G., Reiter K., Schoen C., Mallet F., Brengel-Pesce K., Pachot A., Mommert M., Pokorn M., Kolnik M., Vincek K., Srovin TP., Bahovec N., Prunk P., Osterman V., Avramoska T., Kuijpers T., Jongerius I., van den Berg JM., Schonenberg D., Barendregt AM., Pajkrt D., van der Kuip M., van Furth AM., Sprenkeler E., Zandstra J., van Mierlo G., Geissler J.
AbstractTo assess and describe the aetiology and management of febrile illness in children with primary or acquired immunodeficiency at high risk of serious bacterial infection, as seen in emergency departments in tertiary hospitals. Prospective data on demographics, presenting features, investigations, microbiology, management, and outcome of patients within the ‘Biomarker Validation in HR patients’ database in PERFORM, were analysed. Immunocompromised children (< 18 years old) presented to fifteen European hospitals in nine countries, and one Gambian hospital, with fever or suspected infection and clinical indication for blood investigations. Febrile episodes were assigned clinical phenotypes using the validated PERFORM algorithm. Logistic regression was used to assess the effect size of predictive features of proven/presumed bacterial or viral infection. A total of 599 episodes in 482 children were analysed. Seventy-eight episodes (13.0%) were definite bacterial, 67 episodes probable bacterial (11.2%), and 29 bacterial syndrome (4.8%). Fifty-five were definite viral (9.2%), 49 probable viral (8.2%), and 23 viral syndrome (3.8%). One hundred ninety were unknown bacterial or viral infections (31.7%), and 108 had inflammatory or other non-infectious causes of fever (18.1%). Predictive features of proven/presumed bacterial infection were ill appearance (OR 3.1 (95% CI 2.1–4.6)) and HIV (OR 10.4 (95% CI 2.0–54.4)). Ill appearance reduced the odds of having a proven/presumed viral infection (OR 0.5 (95% CI 0.3–0.9)). A total of 82.1% had new empirical antibiotics started on admission (N = 492); 94.3% proven/presumed bacterial (N = 164), 66.1% proven/presumed viral (N = 84), and 93.2% unknown bacterial or viral infections (N = 177). Mortality was 1.9% (N = 11) and 87.1% made full recovery (N = 522). Conclusion: The aetiology of febrile illness in immunocompromised children is diverse. In one-third of cases, no cause for the fever will be identified. Justification for standard intravenous antibiotic treatment for every febrile immunocompromised child is debatable, yet effective. Better clinical decision-making tools and new biomarkers are needed for this population. What is Known:• Immunosuppressed children are at high risk for morbidity and mortality of serious bacterial and viral infection, but often present with fever as only clinical symptom.• Current diagnostic measures in this group are not specific to rule out bacterial infection, and positivity rates of microbiological cultures are low. What is New:• Febrile illness and infectious complications remain a significant cause of mortality and morbidity in HR children, yet management is effective.• The aetiology of febrile illness in immunocompromised children is diverse, and development of pathways for early discharge or cessation of intravenous antibiotics is debatable, and requires better clinical decision-making tools and biomarkers.