In children and young people up to 16 years of age with a petechial rash, can non-specific laboratory tests (C-reactive protein, white blood cell count, blood gas) help to confirm or refute the diagnosis of meningococcal disease?
Bibliographic information / Study type & evidence / Study details / Number of patients / Patient characteristics / Intervention & comparison / Follow-up & outcome / Results & effect size / Reviewer commentBaker et al.,
1989 43 / Prospective cohort study
Evidence level: 2+ / Aim: To determine the incidence of meningococcal disease in children with fever and petechiae, to determine the clinical predictors of meningococcal disease.
Setting: children’s hospital in the US (1982–1983). / 190 children with fever and petechiae. / Inclusion criteria:
–presence of fever or history of fever (>38°C), –a petechial rash
–age less than 21 years.
Age range: 3 months to 15 years.
All except one patient was hospitalized.
Excluded children with purpura fulminans and known bleeding diathesis; excluded neonates.
Meningococcal disease was diagnosed by detection of Neisseria meningitidis from blood or cerebrospinal fluid culture. / Clinical information about specific signs and symptoms of were available from medical records of patients.
Laboratory evaluation included:
–complete white blood cell count (wbc) with differential and platelet count
–CSF examination
–blood, CSF cultures. / Outcome: diagnosis of meningococcal disease.
–13/190 [7%] had meningococcal disease.
5 children had meningococcal ‘bacteraemia’.
4 children had meningococcal ‘bacteraemia’ and meningitis
4 children had meningococcal meningitis.
–15/190 [8%] had invasive bacterial illness (1 child had invasive disease with Haemophilus influenzae and 1 child with Streptococcus pneumoniae).
–39/190 [20.5%] had non-bacteraemic disease.
–20 children had localised bacterial infections: 19 Streptococcus pyogenes pharyngitis, 1 child Escherichia coli UTI.
–28 children had documented viral infection, mostly respiratory viruses.
–136/190 [71.5%] had no aetiological agent identified.
Compared laboratory investigations in a total of 54 children documented aetiological agent: those with invasive bacteria disease (15 children) and those with non-bacteraemic disease with defined viral or bacterial aetiology (39 children). Prevalence of invasive bacterial illness in this subgroup is 28%.
Patients with invasive bacterial disease had significantly higher peripheral wbc count and absolute immature polymorphonuclear neutrophil count (band forms) compared with non-bacteraemic illness:
–mean wbc count (range): 17,600 cells/µl (3,300–31,100) with invasive bacterial disease v 11,600 cells/µl (2,800–30,200) with non-bacteraemic illness, P = 0.005.
–mean peripheral band count (absolute number of cells/µl and range): 3,717 (0–18,038) with invasive bacterial disease v 523 (0–5,943) with nonbacteraemic illness, P < 0.001.
–CSF wbc count (no of children with > 7 cells/µl): 9 with invasive bacterial disease v 2 with nonbacteraemic illness, P < 0.001.
Indicator / Se
(%) / Spe
(%) / PPV (%) / NPV* / +ve*LR / –ve*
LR
Peripheral wbc count > 15,000 cells/µl / 67 / 85 / 63 / 87% / 4.5 / 0.39
Peripheral absolute band form > 500 cells/µl / 80 / 74 / 55 / 91% / 3.0 / 0.27
Cerebrospinal fluid pleocytosis
(>7 cells/µl) / 53 / 95 / 80
Any of the above / 93 / 62 / 48 / 2.44 / 0.11
Fever and petechiae: indicators of invasive bacterial disease in children with documented microbiological pathogen (Baker et al., 1989)
Se, sensitivity’; Spe, specificity, PPV, positive predictive value;
NPV, negative predictive value; LR, likelihood ratio, * NCC–WCH analysis. / Funding:
Not reported.
Reviewer extracted data only for interventions of interest for the clinical question.
Data about signs and symptoms are reported in the signs and symptoms review.
Study analysed the predictive values of investigations as indicators of invasive bacterial illness for children with confirmed microbiological diagnosis (54 children). Sample size is small with no confidence intervals reported.
The prevalence of invasive bacterial illness in this subgroup is higher than in the total study population: 28% versus 8% which affects diagnostic accuracy results. Also affects the generalisability of these results to a population of children who present with fever and petechiae, the majority of whom will not have a cause identified.
Wells et al.,
2001 44 / Prospective cohort study
Evidence level: 2+ / Aim: To determine whether it is possible to predict with children with a non-blanching rash have meningococcal disease based on clinical signs and laboratory investigations at the time of presentation.
Setting: Children’s Accident and Emergency Department in the UK (1998–1999). / 233 children / 233 infants and children aged
15 years or less presenting to the emergency department with a non-blanching rash: petechiae and/or purpura. 15 children excluded, so 218 children analysed.
–175 children had petechiae only [80%].
Of these 4 children had meningococcal disease and 171 children did not have meningococcal infection.
43 children [20%] had petechiae and purpura. Of these 20 had meningococcal disease and 23 did not have meningococcal disease.
Petechiae defined as non-blanching spots in the skin, less than 2 mm in diameter, and known to be new in onset.
The lesions were classed as purpura if
they were more than 2 mm in
diameter.
Excluded 15 children with an obvious alternative diagnosis:
–11 with Henoch Schonlein purpura
–1 child with idiopathic thrombocytopenic purpura
–1 child with haemolytic uraemic syndrome
–1 child with acute leukaemia
–1 child with clotting disorder.
Meningococcal infection was defined using the PHLS Communicable
Disease Surveillance Centre
enhanced surveillance for
meningococcal disease definition of
a positive blood, CSF, or skin culture
for Neisseria meningitidis, Gram
negative diplococci in CSF, or
positive PCR for meningococcal DNA from blood or CSF. / The following data were recorded:
–presenting symptoms and signs including details of the rash
–laboratory tests including full blood count, differential white cell count, CRP, clotting studies, blood culture, PCR, CSF culture, PCR and biochemistry when lumbar puncture performed.
Signs and symptoms recorded included axillary temperature, blood
pressure, capillary refill time, and
details of the rash (size and
distribution). / Outcome: diagnosis of meningococcal disease.
–24/218 [11%] had laboratory proven meningococcal disease.
Children with meningococcal infection were more likely to have an:
–abnormal neutrophil count
OR 2.7 [95% CI 1.1 to 6.5]
–abnormally prolonged INR:
OR 30 [95% CI 9.9 to 91]
compared with children who did not have meningococcal disease.
A substantial minority of children without meningococcal disease showed these features.
–No child with a CRP < 6 mg/l [90/183] had meningococcal infection.
Table of investigations (Wells et al., )
Investigation
(% done) / Non-meningo-
coccal
(n = 194) / Meningo-coccal
(n = 24) / Odds ratio
[95% CI]
Total white cell count (x109/l) (97%)
Normal (4–11) / 104 (91%) / 10 (9%)
Abnormal / 83 (86%) / 14 (14%) / 1.8 [0.74 to 4.2]
Neutrophils (x109/l)(97%)
Normal (2–7.5) / 116 (93%) / 9 (7%)
Abnormal / 71 (83%) / 15 (17%) / 2.7 [1.1 to 6.5]
CRP (mg/l) (84%)
<6 / 90 (100%) / 0 (0%) / 0 [0 to 3]
6–99 / 70 (89%) / 9 (11%)
>99 / 6 (43%) / 8 (57%)
Ability of the investigations to predict meningococcal infection
Variable / Sensitivity % / Specificity % / PPV
% / NPV
%
Abnormal white count / 58
(39 to 78) / 56
(48 to 63) / 14
(7 to 21) / 91
(84 to 99)
Abnormal neutrophil count / 68
(49 to 88) / 62
(55 to 69) / 17
(9 to 25) / 94
(87 to 100)
CRP > 6 mg/l / 100
(96 to 100) / 54
(47 to 62) / 18
(10 to 26) / 100
(92 to 100)
CRP
6–99 mg/l* / 52% / 58% / 11% / 92%
CRP > 99 mg/l* / 47% / 96% / 57% / 95%
95% CI in brackets; PPV, positive predictive value; NPV, negative predictive value.
NCC–WCH analysis:
Abnormal white cell count:
–positive likelihood ratio: 1.32
–negative likelihood ratio: 0.75
Abnormal neutrophil count:
–positive likelihood ratio: 1.79
–negative likelihood ratio: 0.52
CRP > 6 mg/l
–positive likelihood ratio: 2.17
Performance characteristics for CRP > 99 mg/l
Meningococcal
disease / No meningococcal disease
CRP >99 mg/l / 8 / 6 / 14
CRP <99 mg/l / 9 / 160 / 169
17 / 166 / 183
–sensitivity: 47%
–specificity: 96%
–positive predictive value: 57%
–negative predictive value: 95%
–positive likelihood ratio: 11.75
–negative likelihood ratio: 0.55
Performance characteristics for CRP 6–99 mg/l
Meningococcal
disease / No meningococcal disease
CRP 6–99 mg/l / 9 / 70 / 79
CRP > 6
or < 99 mg/l / 8 / 96 / 104
17 / 166 / 183
–sensitivity: 53%
–specificity: 58%
–positive predictive value: 11%
–negative predictive value: 92%
–positive likelihood ratio: 1.26
–negative likelihood ratio: 0.81
38% of children without meningococcal disease also had an abnormal neutrophil count, and the diagnostic accuracy of an abnormal neutrophil count or an abnormal white blood cell count was low. / Funding:
Not reported.
Reviewer extracted data only for interventions of interest for the clinical question.
Data about signs and symptoms are reported in the signs and symptoms review.
Authors note that the incidence of meningococcal disease is high: the study was carried out before the men C vaccine campaign.
Authors acknowledge that data were incomplete.
Numbers too small for multivariate analysis, so univariate analysis only reported.
Clinical features are useful predictors of meningococcal disease. Investigations were less useful:
Total white count did not distinguish between those with and without meningococcal disease.
A normal CRP seems to be a useful predictor of those who do not have meningococcal disease.