After effects of bacterial meningitis and meningococcal disease: how and why
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Transcript of After effects of bacterial meningitis and meningococcal disease: how and why
After effects of bacterial meningitis and meningococcal disease: how
and why?
Dr Nelly Ninis
What happens in invasive bacterial infections
- Meningitis
- Septicaemia
- And afterwards
The Bacteria
Meningococcus
Pneumococcus
GAS
Pseudomonas / staphylococcus
Infection – the start
Viruses
Common colds
Flu
C’Pox
Toxins
Cause inflammatory explosion of immune system
More toxins in blood = worse disease
Antibiotics kill bacteria not toxins
Once toxins detonate the immune system – antibiotics, supportive care and time
SEPTICAEMIA
MENINGITIS
Prodrome
Cardiovascular failure
CNS failure
MD – disease development
Rash comes at some point
Meningitis
Complications
Brain swelling
Vessel ( vascular ) complications- stroke
Effusions
Obstruction of flow of CSF
Intracranial pressure
Septicaemia
Inflammation in the blood vessels throughout the body
Rapid onset multi-organ failure
Blood vessels are targetted
The Rash
Infection
Microbial Products(exotoxin/endotoxin)
Cellular Responses
OxidasesPlatelet
ActivationKinins
Complement
Coagulopathy/DICVascular/Organ System Injury
Multi-Organ Failure
Death
Endothelial damage Endothelial damage
CoagulationActivation
CytokinesTNF, IL-1, IL-6
Pathogenesis of Severe Sepsis: Inflammation/Coagulation are Linked
Table 3: Median times of onset of clinical features prior to hospital admission (redbars show age-specific median times of first presentation to a primary carephysician).
Age < 1 year Age 1 – 4 years Age 5 – 14 years Age 15 - 16 yearsHoursfromonset Median
(IQR)Median(IQR)
Median(IQR)
Median(IQR)
0 - 4 FeverMiserable/irritablePoor feedingNausea/vomitingDrowsySore throat/coryza
0 (0, 6)0 (0, 7)1 (0, 9)1 (0, 11)3.5 (0, 14)4 (0, 14)
FeverMiserable/irritableNausea/vomitingDecreased appetiteDrowsy
0 (0, 3)2 (0, 10)3 (0, 11)3 (0, 12)4 (0, 11)
HeadacheFever
0 (0, 12)3 (0, 12)
HeadacheSore throat/coryza
0 (0, 1.5)0 (0, 10)
DiarrhoeaAbnormal colourRespiratory distressFloppy toneLimb pain
5 (0, 9)5 (0, 18)6 (0, 16)6 (1, 19)7 (1, 19)
5 - 8
RashCold extremities
8 (3.5, 16)8 (1, 20)
Limb/joint painSore throat/coryzaRespiratory distressHeadacheAbnormal colour
5 (0, 12)7 (1, 16)7 (1, 17)7 (1, 22)8.5 (4, 18)
Abnormal colourDecreased appetiteSore throat/coryzaLimb/joint painGeneral aches
5 (0, 22)5.5 (1, 17)7 (0, 15)7 (0, 15)7 (1, 18)
General achesFever
5.5 (0, 19)6 (1, 13)
General achesRashCold extremitiesGeneral achesSeizure
9 (4, 17)9 (6, 16)9 (2, 17)9 (4, 17)9 (1, 18)
9-12
DiarrhoeaPhotophobiaConfusion/delirium
10 (6, 14)10 (6, 26)10.5 (5,17)
DrowsyCold extremitiesMiserable/irritableConfusion/delirium
9 (1, 21)11.5 (6, 21)12 (3, 21.5)12 (8, 24)
Nausea/vomitingDecreased appetiteLimb/joint painDiarrhoea
9 (3, 19)10 (3, 23)11 (3, 22)12 (8, 24)
Rash 14 (8, 21)13-16 Neck stiffnessPhotophobiaUnconsciousBulging fontanelle
13 (3, 22)13 (5, 18)15 (11, 15)16 (4, 22)
FloppyNeck stiffness
13 (8, 19)13 (8, 20)
Neck stiffness 15 (7, 25)
Miserable/irritableNeck stiffnessCold extremitiesDrowsyAbnormal colourRespiratory distress
13 (2, 23)13 (6, 25)14 (6, 27)14 (7, 24)15 (1, 24)15 (13, 16)
Rash 18.5 (12,27)
17-20 Seizure 17 (15, 32) PhotophobiaDiarrhoea
17 (5, 37)20 (20, 25)
21-24 Unconscious 23 (17, 43) Unconscious 21(13.5, 49) PhotophobiaConfusion/deliriumSeizure
21 (8, 38)24 (13, 28)24 (24, 27)
>24 SeizureRespiratory distress
24.5 (8, 66)35 (20, 44)
Unconscious 25 (17, 37)
Treatment
© Imperial College London
Treatment
Management of meningococcal disease 1940–1980s: Penicillin and pray
Recognition of rash
Penicillin
Counsel parents
Hope and prayer
© Imperial College London
Purpura Fulminans
Topical treatments
Fasciotomies
Anti-toxins
Anti- clotting
NOTHING WORKS
After Effects
Cohort study of children aged 3-16 years with MD admitted to 3 PICUs and 22 general paediatric wards in the London area
Parents and children seen 2-5 days following hospital admission, and followed up following discharge at 3 months (postal questionnaire) and 12 months (interview)
Psychiatric risk assessed in children (SDQ), parents (GHQ) and both (IES)
Sample
70/78 (89%) (36 boys; 34 girls) consecutive admissions for meningococcal disease
52 PICU
18 Non-PICU
Median age at follow-up: 6.8 years
(IQR: 4–12 years)
Psychiatric assessment of children 3–16 years admitted with meningococcal disease, London
Summary: 50% of children develop mostly new psychopathology following MD (primarily depressive and anxiety-related disorders). In 25% this persisted at one year.
Outcomes in children and parents, 3 months and 12 months post discharge
Children < 6y Children >6y Parents
3 monthspost discharge
12% had PTSD
Psychological symptoms linked to: PICU admission, illness severity, similar symptoms in parents and pre-morbid psychological symptoms
MD associated with emotional and hyperactivity symptoms
~50% mothers and ~25% fathers had PTSD symptoms
12 monthspost discharge
11% children at risk for PTSD
Psychological symptoms linked to illness-related changes in parenting
23% mothers and 11% fathers at high risk for PTSD
Maternal PTSD linked to paternal PTSD
1 child developed PTSD
22% scored above cut-off for psychiatric disorder
Problems: tantrums, difficult to manage, sleep problems, fears and feeding problems
50% at least one disorder15% major depression10% minor depression7% adjustment disorder10% oppositional defiant disorder5% phobic disorder2% panic disorder2% transient psychotic disorder
Psychological after effects in children and their parents
Garralda ME, et al. Pediatr Crit Care Med. 2009;10(6):675-80; Shears D, et al. J Am Acad Child Adolesc Psychiatry, 2007;46(1):76-82; Shears D, et al. Pediatr Crit Care Med. 2005;6:39-43.
Admission to Paediatric Intensive Care
Major stressful event for child and their family
Families experience overwhelming shock and disbelief, accompanied by feelings of helplessness
Parents faced with worries about outcome of treatment and acute life-threatening illness in their child
PICU experience is intense—sights and sounds in the environment, and seeing other children undergo painful, distressing procedures or even death
PICU admission imposes an immense burden on critically ill children, their siblings, parents and other family members, potentially increasing risk of adverse psychological outcomes
Clinical evidence of neuropsychological effects
Prospective observational case-control study of 88 children aged 5-16y admitted to ICUs between 2007-2010 c.f. 100 healthy controls
Follow-up 3-6 months after PICU admission
Demographic and critical illness details were obtained, and children were assessed using tests of intellectual function, memory, and attention
Questionnaires addressing academic performance were returned by teachers
Measurement tools IQ:
Wechsler Abbreviated Scale of Intelligence (WASI; The Psychological Corporation, 1999) – 6 yrs and older
Wide Range Intelligence Test (WRIT; Glutting et al) – 5 yr olds
Verbal memory and learning: Children’s Memory Scale (CMS; Cohen, 1997)
Visual memory, learning and attention: Cambridge Neuropsychological Test Automated Battery (CANTAB; Cambridge Cognition, 2006)
Psychiatric risk
0
10
20
30
40
50
60
70
% at risk for PTSD
Septic Illness M-Encephalitis
Patient Ctr
PTSD risk
Neuropsychologic function after PICU admission
Cognitive function
Als LC, et al. Crit Care Med. 2013;41(4):1094-1103.
• Summary: Meningoencephalitis and sepsis particularly associated with reduced neuropsychological function
Deteriorating academic performance in school post PICU (Sepsis worst performance)
Number of days off since returning to school 11.50 ME 9.00 Sepsis 6.00 Patient Contr
Als LC, et al. Crit Care Med. 2013;41(4):1094-1103.
Conclusions from this studyAls LC, et al. Crit Care Med. 2013;41(4):1094-1103.
In children with sepsis, meningo-encephalitis and other disorders admitted to PICU:
PICU admission was followed by an increase in child psychopathology persisting at 12 months
Children with more severe illness, those with septic shock and those with impairing pre-morbid emotional and behavioural problems have the highest risk
Changes in parenting and maternal mental health may contribute to the persistence of the psychological morbidities and may be potentially treatable
What is known about the outcomes of meningitis?
CNS infections acquired in childhood lead to impairment in motor and cognitive functions (Carter et al. 2003)
12-year follow-up of children with bacterial meningitis found general performance and executive function impairments in comparison to controls (Anderson et al. 2004)
Academic limitations identified in 32% children 4–10 years following bacterial meningitis (Koomen et al. 2005)
Teenagers from national incidence study of infantile meningitis in England & Wales passed significantly fewer 16+ exams compared with controls (De Louvois et al. 2007)
Long-term outcomesSurvivors of meningococcal septic shock that required PICU treatment
Long-term skin scarring & orthopaedic sequelae
n=170, 4-16 years after discharge
Long-term overall outcome and health-related QoL
n=120, 3-18 years after discharge
Long-term health status
n=120, 10 years after discharge
48% scarring61% (73 of 120) had 1 of 4 major adverse outcome variables
35% one or more neurological impairment
8% amputations26 of 73 had >1 major adverse outcome
3% severe mental retardation
6% lower limb length discrepancy
47 of 73 had 1 major adverse outcome
• 13 major physical• 19 mild neurological• 7 problem behaviour• 8 IQ<85
3% epilepsy
All had higher severity of illness scores
Longer LOS and higher severity score predicted worse outcome
2% hearing loss
6% focal neurology (i.e. paresis)
Buysse CMP, et al. Arch Dis Child 2009;94:381–386.
Buysse CMP, et al. Crit Care 2010;14:R124.
Buysse CMP, et al. Arch Pediatr Adolesc Med 2008;162(11):1036-1041.
245 survivors of group B meningococcal disease (3 years after disease)
Age and sex matched healthy controls 2% profound bilateral SNHL 5% moderate bilateral SNHL 6% any SNHL (control < 1%) 4% speech/communication difficulty IQ, memory and executive function significantly worse Significantly higher risk of mental health disorder
(26% vs 10% in controls)
Lancet Neurol 2012;11:774–783.
Outcomes in adolescents
Outcomes from MD - 2003
Cohort of 101 case-control pairs
Short and long term memory and attention deficits
Deficit in cognitive flexibility Higher rates of depression in MCD sufferers This should be attended to in follow up
18 , 36 month follow up of cohort
57% of survivors had physical disability- much higher than studies with younger children
- Serogroup C disease, septicaemia had worse physical outcome
Adolescents who were younger at time of MD- greater degree of cognitive deficit at follow up
- Development of “social brain” in adolescence
QoL worse than peers
• Mental Health – twice as many survivors had depressive score in clinical range
• Social support – lower social support scores
• Educational outcomes- fewer passes at GCSE, 2x more likely to have failed exam in past year
Wide range of significant sequelae from Invasive Meningococcal Disease
1. Singhi PD, et al. In: Helfaer MA, et al, eds. Rogers’ Handbook of Pediatric Intensive Care. Philadelphia, PA: Lippincott, Williams & Wilkins; 2009:500-519; 2. Brandtzaeg P. In: Frosch M, et al, eds. Handbook of Meningococcal Disease: Infection Biology, Vaccination, Clinical Management. Weinheim, Germany: Wiley-VCH Verlag GmbH & Co. KGaA; 2006:427-479; 3. Granoff DM, et al. In: Kleigman RM, et al, eds. Nelson Textbook of Pediatrics, 19th ed. Philadelphia, PA: Saunders Elsevier; 2011;929-935; 4. Judge D, et al. Intensive Care Med. 2002;28:648-650; 5. Anderson V, et al. J Pediatr Psychol. 2004;29:67-81; 6. Bedford H, et al. BMJ. 2001;323:533-536.
Subacute and Chronic Sequelae of IMD Hearing loss/deafness Ossification of the inner ear Blindness Brain abscess Seizure disorders/epilepsy Cranial nerve palsies Hemiparesis or quadriparesis Obstructive hydrocephalus Neuropsychiatric disorders
Post-traumatic stress disorder Learning deficits Motor deficits/ataxia Neurodevelopment deficits Cerebral infarction/stroke Cerebral arterial or venous thrombosis Subdural effusion
Limb loss Digit amputation Growth plate damage Skin grafts/scar repair Necrotic skin loss Arthritis Renal impairment Chronic organ damage Adrenal failure Cognitive impairment Nonsuppurative complications—eg,
immune complex disorders, vasculitis, arthritis
Empyema Endocrinopathies
Some sequelae do not become evident until years after the illness, long after routine follow-up has ceased.
In Conclusion
Surviving sepsis and meningitis is difficult business
Patients are very inspiring and capable and able
Education about after effects very important
Thank you