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01-04-2021 | Review

Shivering has little diagnostic value in diagnosing serious bacterial infection in children: a systematic review and meta-analysis

Authors: Maud Vandenberk, Kasper De Bondt, Emma Nuyts, Jaan Toelen, Jan Y Verbakel

Published in: European Journal of Pediatrics | Issue 4/2021

Abstract

Early diagnosis of serious bacterial infections (SBI) is important for improving outcome of morbidity and mortality in children. A systematic review was conducted to examine if shivering had any value in diagnosing serious bacterial infection. We split our population (0–18 years old) into two categories depending on the presence of a known malignancy. The databases of Medline, Embase, Cinahl, and Web of Science were searched from inception until July 2019. The quality was assessed with the QUADAS-2 tool. Two by two tables were created, extracting the number of true positive (TP), true negative (TN), false positive (FP), and false negative (FN) regarding shivering and SBI, by 2 authors independently. Sensitivity, specificity, likelihood ratios, and their 95% confidence intervals were calculated using the MetaDATA Shiny app. In a population with known malignancy, we found a +LR of 3.47 (95% CI 2.58–4.36) for a serious bacterial infection when shivering was present, implying an increase of 25–30% possibility for a serious bacterial infection. In children without malignancy, diagnostic accuracy of shivering was poor.

Conclusion: Shivering is of limited use to diagnose serious bacterial infection in children without malignancy. Nevertheless, in children with known malignancy, it can be useful as an alarm signal.

What is Known:

• In the NICE guidelines for febrile illness in children, “shivering” is considered as an intermediate risk factor (“amber” sign) for a serious illness.

• A systematic literature search conducted in 2007 investigating the correlation between shivering in a febrile child and the presence of a serious bacterial infection could include only one study.

What is New:

• Based on the results of this systematic review, shivering has little diagnostic value in children without malignancy but can be useful as an alarm sign of serious bacterial infection in children with known malignancy.

• In case of absence of shivering, serious bacterial infection cannot be ruled out.

Available only for authorised users

UNICEF TUNIG for CME (2015) Levels and trends in child mortality 2019. WHO. https://www.unicef.org/media/60561/file/UN-IGME-child-mortality-report-2019.pdf Accessed 28 October 2020.

Ladhani S, Pebody RG, Ramsay ME, Lamagni TL, Johnson AP, Sharland M (2010) Continuing impact of infectious diseases on childhood deaths in England and Wales, 2003-2005. Pediatr Infect Dis J 29(4):310–313. https://doi.org/10.1097/INF.0b013e3181d73322CrossRefPubMed

Launay E, Gras-Le Guen C, Martinot A, Assathiany R, Blanchais T, Mourdi N et al (2010) Suboptimal care in the initial management of children who died from severe bacterial infection: a population-based confidential inquiry. Pediatr Crit Care Med 11(4):469–474. https://doi.org/10.1097/PCC.0b013e3181ce752eCrossRefPubMed

Van Den Bruel A, Thompson MJ, Haj-Hassan T, Stevens R, Moll H, Lakhanpaul M et al (2011) Diagnostic value of laboratory tests in identifying serious infections in febrile children: systematic review. BMJ 342:d3082. https://doi.org/10.1136/bmj.d3082CrossRefPubMed

Brent AJ, Lakhanpaul M, Thompson M, Collier J, Ray S, Ninis N, Levin M, MacFaul R (2011) Risk score to stratify children with suspected serious bacterial infection: observational cohort study. Arch Dis Child 96(4):361–367. https://doi.org/10.1136/adc.2010.183111CrossRefPubMed

Boron WF, Boulpaep EL. (2005) Medical physiology: a cellular and molecular approach (updated edition). In: Medical physiology: a cellular and molecular approach (updated edition). Saunders, US.

Lee CC, Wu CJ, Chi CH, Lee NY, Chen PL, Lee HC, Chang CM, Ko NY, Ko WC (2012) Prediction of community-onset bacteremia among febrile adults visiting an emergency department: Rigor matters. Diagn Microbiol Infect Dis 73(2):168–173. https://doi.org/10.1016/j.diagmicrobio.2012.02.009CrossRefPubMed

Davis T (2013) NICE guideline: feverish illness in children - assessment and initial management in children younger than 5 years. Arch Dis Child Educ Pract Ed 98(6):232–235. https://doi.org/10.1136/archdischild-2013-304792CrossRefPubMed

Lumsden DE, de la Morandière KP (2007) Rigors in febrile children may be associated with a higher incidence of serious bacterial infection. EMJ 24(9):663. https://doi.org/10.1136/emj.2007.052282CrossRefPubMed

10.

Gulliford MC, Sun X, Charlton J, Winter JR, Bunce C, Boiko O, Fox R, Little P, Moore M, Hay AD, Ashworth M, SafeAB Research Group (2020) Serious bacterial infections and antibiotic prescribing in primary care: cohort study using electronic health records in the UK. BMJ Open 10(2):e036975. https://doi.org/10.1136/bmjopen-2020-036975CrossRefPubMedPubMedCentral

11.

Nijman RG, Vergouwe Y, Thompson M, van Veen M, van Meurs AH, van der Lei J, Steyerberg EW, Moll HA, Oostenbrink R (2013) Clinical prediction model to aid emergency doctors managing febrile children at risk of serious bacterial infections: diagnostic study. BMJ 346:f1706. https://doi.org/10.1136/bmj.f1706CrossRefPubMedPubMedCentral

12.

Irwin AD, Grant A, Williams R, Kolamunnage-Dona R, Drew RJ, Paulus S, Jeffers G, Williams K, Breen R, Preston J, Appelbe D, Chesters C, Newland P, Marzouk O, McNamara PS, Diggle PJ, Carrol ED (2017) Predicting risk of serious bacterial infections in febrile children in the emergency department. Pediatrics 140(2):e20162853CrossRefPubMed

13.

Rosenfeld-Yehoshua N, Barkan S, Abu-Kishk I, Booch M, Suhami R, Kozer E (2018) Hyperpyrexia and high fever as a predictor for serious bacterial infection (SBI) in children-a systematic review. Eur J Pediatr 177(3):337–44.14CrossRefPubMed

14.

Higgins JP, Thompson SG, Deeks JJ, Altman DG (2003) Measuring inconsistency in meta-analyses. BMJ 327(7414):557–560. https://doi.org/10.1136/bmj.327.7414.557CrossRefPubMedPubMedCentral

15.

Freeman SC, Kerby CR, Patel A, Cooper NJ, Quinn T, Sutton AJ (2019) Development of an interactive web-based tool to conduct and interrogate meta-analysis of diagnostic test accuracy studies: MetaDTA. BMC Med Res Methodol 19(1):81. https://doi.org/10.1186/s12874-019-0724-xCrossRefPubMedPubMedCentral

16.

Chu H, Cole SR (2006) Bivariate meta-analysis of sensitivity and specificity with sparse data: a generalized linear mixed model approach. J Clin Epidemiol 59(12):1331–1332 author reply 2-3CrossRefPubMed

17.

Bates D, Maechler M, Bolker B, Walker S, Haubo Bojesen Christensen R, Singmann H, et al (2018) lme4: Linear mixed-effects models using ‘Eigen’ and S4. R package version 1.1-18-1. https://CRAN.R-project.org/package=lme4

18.

Partlett C, Takwoingi Y (2016) Meta analysis of test accuracy studies in R: a summary of user-written programs and step-by-step guide to using glmer. Version 1.0 Available from: https://methods.cochrane.org/sdt/software-meta-analysis-dta-studies

19.

Jackson C (2018) msm: Multi-state Markov and hidden Markov models in continuous time. R package version 1.6.6. https://CRAN.R-project.org/package=msm

20.

Whiting PF, Weswood ME, Rutjes AWS, Reitsma JB, Bossuyt PNM, Kleijnen J (2006) Evaluation of QUADAS, a tool for the quality assessment of diagnostic accuracy studies. BMC Med Res Methodol 6:9. https://doi.org/10.1186/1471-2288-6-9CrossRefPubMedPubMedCentral

21.

Ammann RA, Hirt A, Lüthy AR, Aebi C (2004) Predicting bacteremia in children with fever and chemotherapy-induced neutropenia. Pediatr Infect Dis J 23(1):61–67CrossRefPubMed

22.

Bartholomew F, Aftandilian C, Andrews J, Gutierrez K, Luna-Fineman S, Jeng M (2015) Evaluation of febrile, nonneutropenic pediatric oncology patients with central venous catheters who are not given empiric antibiotics. J Pediatr 1 166(1):157–162

23.

Agyeman P, Aebi C, Hirt A, Niggli FK, Nadal D, Simon A, Ozsahin H, Kontny U, Kühne T, Beck Popovic M, Leibundgut K, Bodmer N, Ammann RA (2011) Predicting bacteremia in children with cancer and fever in chemotherapy-induced neutropenia: Results of the prospective multicenter spog 2003 fn study. Pediatr Infect Dis J 30(7):e114–e119CrossRefPubMed

24.

Lucas KG, Brown AE, Armstrong D, Chapman D, Heller G (1996) The identification of febrile, neutropenic children with neoplastic disease at low risk for bacteremia and complications of sepsis. Cancer 77(4):791–798CrossRefPubMed

25.

Ammann RA, Hirt A, Lüthy AR, Aebi C (2003) Identification of children presenting with fever in chemotherapy-induced neutropenia at low risk for severe bacterial infection. Med Pediatr Oncol 41(5):436–443. https://doi.org/10.1002/mpo.10320CrossRefPubMed

26.

Doganis D, Asmar B, Yankelevich M, Thomas R, Ravindranath Y (2013) Predictive factors for blood stream infections in children with cancer. Pediatr Hematol Oncol 30(5):403–415. https://doi.org/10.3109/08880018.2013.778379CrossRefPubMed

27.

Esbenshade AJ, Pentima MC, Zhao Z, Shintani A, Esbenshade JC, Simpson ME, Montgomery KC, Lindell RB, Lee H, Wallace A, Garcia KL, Moons KG, Friedman DL (2015) Development and validation of a prediction model for diagnosing blood stream infections in febrile, non-neutropenic children with cancer. Pediatr Blood Cancer 62(2):262–268. https://doi.org/10.1002/pbc.25275CrossRefPubMed

28.

Ke ZY, Xu L, Zhang TT, Mo YL, Huang LB, Zhang XL, Luo XQ (2010) A prospective study of febrile episodes in inpatient children on chemotherapy. Pediatr Infect Dis J 29(10):968–970. https://doi.org/10.1097/INF.0b013e3181e32ab2CrossRefPubMed

29.

Ayoola OO, Adeyemo AA, Osinusi K (2002) Predictors of bacteraemia among febrile infants in Ibadan, Nigeria. J Health Popul Nutr 20(3):223–229PubMed

30.

Erell Y, Youngster I, Abu-Kishk I, Kozer E (2017) Shivering in febrile children: frequency and usefulness in predicting serious bacterial infections - a prospective case-control study. J Pediatr 190:258–260.e1. https://doi.org/10.1016/j.jpeds.2017.06.075CrossRefPubMed

31.

Shu LH, Xu JJ, Wang S, Zhong HQ, Dong XY, Jiang K, Zhang HY, Xiong Q, Wang C, Sun T, Sun C, Lu Q (2015) Distribution of pathogenic microorganisms and its relationship with clinical features in children with community-acquired pneumonia. Zhongguo Dang Dai Er Ke Za Zhi 17(10):1056–1061PubMed

32.

Tal Y, Even L, Kugelman A, Hardoff D, Srugo I, Jaffe M (1997) The clinical significance of rigors in febrile children. Eur J Pediatr 156(6):457–459. https://doi.org/10.1007/s004310050638CrossRefPubMed

33.

McGee S (2002) Simplifying likelihood ratios. J Gen Intern Med 17(8):646–649. https://doi.org/10.1046/j.1525-1497.2002.10750.xCrossRefPubMed

34.

Horeczko T, Enriquez B, McGrath NE, Gausche-Hill M, Lewis RJ (2013) The pediatric assessment triangle: accuracy of its application by nurses in the triage of children. J Emerg Nurs 39(2):182–189. https://doi.org/10.1016/j.jen.2011.12.020CrossRefPubMed

35.

Kerkhof E, Lakhanpaul M, Ray S, Verbakel JY, Van den Bruel A, Thompson M, Berger MY, Moll HA, Oostenbrink R; European Research Network on recognising serious InfEctions (ERNIE) members. (2014) The predictive value of the NICE “red traffic lights” in acutely ill children. PLoS One 9(3):e90847. doi: https://doi.org/10.1371/journal.pone.0090847

36.

De S, Williams GJ, Teixeira-Pinto A, Macaskill P, McCaskill M, Isaacs D et al (2015) Lack of accuracy of body temperature for detecting serious bacterial infection in febrile episodes. Pediatr Infect Dis J 34(9):940–944CrossRefPubMed

Title: Shivering has little diagnostic value in diagnosing serious bacterial infection in children: a systematic review and meta-analysis
Authors: Maud Vandenberk
Kasper De Bondt
Emma Nuyts
Jaan Toelen
Jan Y Verbakel
Publication date: 01-04-2021
Publisher: Springer Berlin Heidelberg
Published in: European Journal of Pediatrics / Issue 4/2021
Print ISSN: 0340-6199
Electronic ISSN: 1432-1076
DOI: https://doi.org/10.1007/s00431-020-03870-7

At a glance: The STEP trials

Springer Medicine

Shivering has little diagnostic value in diagnosing serious bacterial infection in children: a systematic review and meta-analysis

Abstract

At a glance: The STEP trials

Springer Medicine

Abstract

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