What Proportion of Children and Young People with Meningococcal Septicaemia Develop Physical

What proportion of children and young people with meningococcal septicaemia develop physical and psychological morbidity?

Bibliographic information / Study type & evidence / Study details / Number of patients / Characteristics of studies/patients / Data collection methods / Follow-up & outcome / Results & effect size / Reviewer comment /
Kaplan et al., 2006 184 / Study type: prospective hospital-based survey (multicentre)
Evidence level: 3 / Aim: to collect demographic, clinical, laboratory, and outcome
information for infants and children who had Neisseria meningitidis infections
of various serogroups and were cared for in 10 pediatric hospitals
Setting: 10 children’s hospitals in the United States, belonging to The US Multicenter Meningococcal Surveillance Study
Group / 159 children / 159 children seen in hospital with systemic infections that were caused by Neisseria meningitidis, from January 1, 2001 through March 15, 2005
-age range: less than 12 months to 19 years
41 children younger than 12 months, 22 children were 12 to 24 months of age
Two (1.3%) patients were ≤ 30 days of age (16 days old with meningitis; 29 days old with bacteraemia). 66% of children were ≤ 5 years of age. The numbers of children decreased with age until 8 years of age, when a slight increase occurred, peaked at 11 years, and declining again through 16 years of age.
-96 (60%) male.
-An underlying condition was present in only 9
(5.6%) patients complement deficiency detected as a result of the meningococcal infection [2], sickle cell disease
[2], congenital hydrocephalus [1], ventricular septal defect [1], lung transplant for cystic fibrosis [1], autoimmune hepatitis [1], and prematurity [1]). One
patient (19 years of age) received the meningococcal
polysaccharide vaccine 1.5 years before onset of this infection (serogroup B). Three secondary cases of meningococcal disease were identified in the daughter of a baby-sitter, a household contact, and a patient in close proximity in the ICU / A standard
data form that included demographic and clinical information and outcome was completed retrospectively
for each infectious episode / Incidence of sequelae during or after hospitalisation / Sequelae of Meningococcal Infection in 146 Surviving
Children During or After Hospitalization:
Hearing loss occurred in 14 children (all ≤10 years of age; 8 ≤ 2 years of age), or 12.5% of those with meningitis. Unilateral deafness occurred in 6 children and bilateral deafness in 8.
Skin necrosis (n= 13; 9 ≤4 years of age) with some requirements for grafting (n=4) was the second most common sequela. Two children had amputations (one in four extremities, one in toes).
Three children had vasculitis, and 1 had pericarditis, all considered manifestations of immune complex disease by the site investigator
Skin necrosis 14, 4 requiring skin grafting.
9 children developed seizures after admission.
4 children developed ataxia and 3 hemiplegia / Funding:
Drs Kaplan and Halasa have received grant support from, and Dr Byington has been a paid speaker for, Sanofi Pasteur
Vermunt et al., 2008 188 / Study type: cohort study
Evidence level: 3 / Aim: to investigate self-esteem and its relation to scars, amputations, and orthopaedic sequelae in children and adolescents long term after meningococcal septic shock (MSS) caused by Neisseria meningitidis
Setting: ErasmusMC-Sophia Children’s Hospital, Rotterdam / 65 children / Homogeneous cohort of children and adolescents (n=65) who survived MSS between 1988 and 2001
-29 children (aged 8 to 11 years, mean 9.4)
13 boys
Scars (n=15):
Face: 3
Trunk: 1
Arms: 6
Legs: 12
Unknown: 3
Amputations (n=2)
One toe: 1
Four toes: 1
Orthopaedic sequelae (n=2)
Lower limb-length discrepancy (3.5 cm): 1
Varus deformity of the right ankle: 1
-36 adolescents (aged 12 to 17 years, mean 14.4
20 boys
Scars (n=18):
Face: 6
Trunk: 4
Arms: 10
Legs: 16
Amputations (n=3)
One finger: 1
One leg below knee: 1
One arm below elbow and two legs, one below and one above knee: 1
Orthopaedic sequelae (n=0)
-reference groups for the SPP-C and SPP-A consisted of normative samples of healthy children and adolescents used to standardise these questionnaires / -Self esteem measured with Duct versions of Harter’s Self Perception Profile for Children (SPP-C) (for ages 8 to 11) and Harter’s Self Perception Profile for Adolescents (SPP-A) (for ages 12 to 17). The questionnaires consist of 36 (for SPP-C) and 40 (for SPP-A) items, which are distributed over 5 domain specific subscales and one global self-worth subscale
-Physical examination performed by paediatric intensivist with special focus on scars, amputations, angular deformities and limb-length discrepancies related to MSS / -Self-esteem subscales:
Scholastic competence
Social acceptance
Athletic competence
Physical appearance
Behavioural conduct
Close friendship
Global Self-Worth / Comparison of levels of self-esteem of MSS children and adolescents vs. reference groups:
MSS boys aged 8 to 11 years obtained a more favourable score on social acceptance compared with reference group boys. No further differences were found for either boys or girls on any of the SPP-C scales.
On SPP-A scales boys aged 12-17 yrs obtained signif. lower mean scores compared with reference boys on 6 of the 7 sub-scales: scholastic competence, social acceptance, athletic competence, physical appearance, close friendship and global self-worth. MSS girls aged 12-17 yrs reported lower scores on 3 of the 7 sub-scales: social acceptance, close friendship and global self-worth.
No significant differences were found for differences between boys and girls for either age group.
Severity of illness, age at time of illness and age at time of follow =up was not significantly correlated with any of the scores.
MSS adolescents with scars reported a significantly lower global self-worth than those without scars. No further effects were found regarding presence of scars.
A significant negative correlation was found between children with scars and score for social acceptance.
On 6 of the 7 domains on the self-esteem questionnaire male (n=16) or female (n=20) adolescents who had survived MSS scored significantly (p<0.05) / Funding:Grant from Hersenstichting Nederland (the Dutch Brain Foundation)
Vermunt et al., 2008 186 / Study type: cohort study
Evidence level: 2+ / Aim: to asses the occurrence of a wide range of behavioural, emotional and post-traumatic stress problems in children and adolescents, long term after septic shock cause by Neisseria meningitidis
Setting: ErasmusMC-Sophia Children’s Hospital, Rotterdam / 89 children / Population: Children who had survived meningococcal septic shock and who had been admitted to the hospital’s PICU between August 1988 and June 2001.
Study sample: Parents and teachers of 6-17 year old children and children aged 11-17 taken from the study population were included.
-Reference groups:
representative Dutch samples form the general population (n= 1639; 760 boys) / Measures of behavioural, emotional and post-traumatic stress:
Child Behaviour Checklist (CBCL) – list of 120 behaviour-related problem items to be rated on a 3-point scale considered over preceding 6 months.
Teachers’ Report Form – mirrors CBCL and is rated for preceding 2 months.
Youth Self-Report (YSR) – follows format of the CBCL, worded in first person for self-completion.
Post Traumatic Stress Problems Scale – consists of 14 items from the CBCL and YSR identified as being related to post-traumatic stress.
All scales have fairly good reliability and internal consistence values. / Follow-up: 4-8 years after illness.
Outcomes:
Behavioural problems
Emotional problems
Post traumatic stress problems
Problem children/deviant behaviour: defined as children scoring above the 90th percentile of the cumulative frequency distributions of the total problem scores obtained from reference groups. / Problem children: Overall no signif. differences in proportions of children scoring in the deviant range in the MSS and reference groups.
For the vast majority of scores on the test scales there were no signif. differences between the 2 groups.
On the CBCL mothers of MSS children reported significantly more problems with somatic complaints than mothers of reference children.
Severity of illness was not found to be a significant predictor of long-term total problems or scale scores, either for the children themselves, their parents or their teachers.
When mothers were the informants age at time of illness appeared to be a signif. predictor of long-term post- traumatic stress, social and total problems (ß=-0.36, p<0.05; ß=-0.32, p<0.05; ß=-1.79, p<0.05 respectively).When fathers were informants young age at time of illness was seen as a signif. predictor of long-term post-traumatic stress, anxious/depressed attention and total problems (ß=-0.33, p<0.05; ß=-0.42, p<0.05; ß=-2.23, p<0.05 respectively).
n=45 completed questionnaires; response rate 74%; 11-17 year olds) and to both parents and teachers of children aged 6-17 years surviving meningococcal septic shock (n=89 parents, response rate 85%; n=61 teachers, response rate 58%). / Funding:
Grant number 14F06.03 from the Hersenstichting Nederland (Dutch Brain Foundation)
Buysse et al., 2008 185 / Study type: prospective cohort
Evidence level: 2 / Aim: to assess health consequences and health –related quality of life (HR-QoL) in children with meningococcal septic shock up to 2 years after discharge form the paediatric intensive care unit and to assess their parents. To determine major predictors of that outcome
Setting: ErasmusMC-Sophia Children’s Hospital, Rotterdam. Tertiary care university hospital / 47 children and their families / All consecutive children with septic shock and purpura requiring intensive care at study hospital between October 2001 and March 2005. Also includes parents of these children.
Reference group – representative sample of 353 children aged 5-13 years and 175 women aged 26-35 years as a reference group for the mothers of children who had survived meningococcal disease. / Health consequences and medical care, measured using standard questionnaire presented during face to face interview plus a general medical examination.
Health-related quality of life (HR QoL) for children and parents measured by the Child Health Questionnaire and the Medical Outcomes Study 36-Item Short Form Health Survey (SF-36). Infant and Toddler QoL Questionnaire used for children aged 0-3 years. / Follow-up: Within 2 years following discharge from PICU.
Outcomes:
Health consequences including physical and psychosocial sequelae.
Quality of life / Health consequences:
Amputation of 3 fingers in one child, amputation of one finger in one child; lower limb shortening in one toddler.
26 children had mild to severe skin scarring following necrosis of skin lesions.
10 children reported pain (lower limbs n=7; headached n=3).
Other on-going problems: behavioural/emotional problems n=6; fatigue n=2; motor skills problems n=1; per equinus n=1; Raynaud phenomenin associated with amputated finger n=1; sleep disturbances n=1; stuttering n=1.
HR QoL ITQoL (0-3 years) (n=19): signif lower scores obtained for MSS children when compared with reference group on 4 of 12 sub-scales namely: physical abilities, general health perceptions, parental impact – emotional and change in health.
CHQ-PF50 (4-17 years) (n=26): signif lower scores obtained for MSS children when compared with reference group on 3 of 14 sub-scales namely: physical functioning, general health perceptions, physical summary.
neurological sequelae were reported for 3/47 children and comprised: motor skills problems n=1; pes equinus n=1; and Raynaud phenomenon at amputated finger n=1.
10/47 children experienced chronic pain (lower limbs, n=7; headache, n=3). Pain was the most frequent chronic symptom. However, in a comparative section of the study, the incidence of pain was found not to be significantly different from the reference class for either age group assessed (children aged 0-3 were compared with a reference group of 410 children aged 3 months to 3 years. Children aged 4-17 years were compared with a reference group of 353 schoolchildren aged 5-13 years). / Funding:
SIGN guideline 27 / Study type: Systematic review
Evidence level 3 / Aim: To describe the morbidities associated with meningococcal disease and the further support and information provision needed by patients as a result of these morbidities. / The review includes 22 studies in total. Of these 9 are relevant to our systematic review. / 9 studies conducted in high-income countries reporting morbidities associated with meningococcal disease. Data collected between 1985 and 2002. Total number of children involved=1251. / Data collection methods included the following for given outcomes:
Hearing loss: auditory brainstem response, play audiometry
Orthopaedic complications: physical examination
Skin complications/scarring: physical examination; questionnaire
Psychosocial complications: battery of tests of neurological function, coordination, cognition and behaviour, QoL questionnaires.
Neurological sequelae: tests of neurological function, physical examination. / Follow-up ranged from 12 weeks to 12 years post hospital discharge.
Outcomes:
Proportion of children with:
Hearing loss
Orthopaedic complications including amputations
Skin complications including scarring
Psychosocial complications including behavioural problems and Quality of Life
Neurological sequelae / Findings:
Based on all relevant included studies:
Hearing loss: Range 1.9% – 15% children (6 studies; n=1088 children)
Orthopaedic complications: 0.25% to 4.6% (4 studies; n=1020 children)
Skin complications including scarring: 3.9% to 6.8% (3 studies; n=1028 children)
Psychosocial complications: QoL: in one study (n=231) 23% respondents rated QoL as worse than before the illness with problems including reduced energy, increased anxiety, reduction in leisure activities and a reduced ability to work. A case control study followed-up participants (n=115 cases and 115 controls) 8-12 years after their illness. Neurodevelopment assessed using a battery of tests of neurological function, coordination, cognition and behaviour. Control group scored higher in all 4 tests. 3 cases vs. 1 control were found to have ADHD, with a further 8 cases vs. 0 controls with possible ADHD. 9 cases vs. 3 controls were identified as having special educational needs, with an additional 29 cases vs. 14 controls being assessed for suspected learning difficulties.
One cohort study: incidence of neurological developmental delay 18/407 children.
(3 studies; 777 children)
Neurological sequelae: 3.9% to 20.7%.
1 cohort study followed up children 1 year after discharge and found 6/29 had neurological problems (3 seizures, 3 ataxia).
1 case-control study identified 4/139 children as having severe neurological complications including microcephaly, spastic quadriplegia, epilepsy and blindness. Significantly more cases than controls performed poorly on measures of coordination, cognition and behaviour.
2 studies report incidence as 8/151 children suffering seizures and 2/51 with neurological sequelae.
(4 studies, 3 contributing to overall proportion; 341 children) / Funding: no conflicts of interest reported.
Buysse et al., ., 2009 187 / Study type: Case series
Evidence level: 3 / Aim: to assess the incidence of skin scarring and orthopaedic sequelae (amputation, limb-length discrepancy) in patients who survived meningococcal septic shock (MSS) in childhood and to determine the severity and predictors of these sequelae