Title: Redefining HIV encephalopathy in children living in SSA
1Redefining HIV encephalopathy in children living
in SSA
Charles RJC Newton Kenya Medical Research
Institute/ Wellcome Trust Collaborative
Programme, Kilifi, Kenya
2Epidemiology of HIV in Children living SSA
- In 2001 2.2 M children infected
- Acquired infection
- Mother (gt95)
- Blood transfusions
- Contaminated needles
- Sexual
3Maternal Transmission
- Cumulative 40
- Breast-feeding
- 10-20
- Accounts for gt40 of the transmission overall
- At birth
- 10-20
- In utero
- 5-10
4Prognosis for Children
- Of those infected
- 35 die by 1 year
- 52 die by 2 years
- Mortality higher in
- East and West Africa
- Mortality likely to be greater in those not in
the trials.
Newell et al Lancet 2004364 1236-43
5Comparison of clinical features of NeuroAIDS in
Western countries
- Adults
- Horizontal acquisition
- Long latency
- Deterioration of mature CNS
- Motor deterioration
- Cognitive decline
- CNS OI frequent
- Brain atrophy
- Cerebrovascular disease common
- Children
- Vertical acquisition
- Short latency
- Impairment of immature CNS
- Progressive motor dysfunction
- Neurodevelopmental decline
- CNS OI infrequent
- Impaired brain growth
- Cerebrovascular disease rare
6Comparison between CNS pathology of HIV infected
children in USA and Cote dIvoire
Bell et al. J Neuropath Exp Neurol 1997 56
686-692
7Definition of HIV encephalopathy in children
- HIV positive child who is
- neurologically normal at baseline
- Meets one of the criteria in the major domains
- Neurologically abnormal at baseline
- Meets two of the criteria in the major domains
- In the absence of another cause for these
features - Working group on ARV and medical management of
infants, children and adolescents Pediatrics
1998 102 105-66
8Major Domains
- Impairment of brain growth
- Decline of cognitive (neurodevelopment) function
- Clinical motor dysfunction
9Impairment of brain growth
- In the absence of other aetiologies
- Documented by either
- Infants with HC lt 5th percentile
- Children lt3 yrs crossing 2 major percentiles from
baseline HC - Children HC falling below lt 5th percentile
- Children with serial neuroimagining studies
showing loss of brain parenchyma
10Decline of neurodevelopment function
- Documented by psychometric testing
- At least 2 individual, valid measurements
separated by at least 1 month - Child lt 3 years
- Fall of 2 SD on a standardized non-screening
developmental assessment - Child gt 3 years
- Fall of at least 1SD on standardised test of
intelligence - Any age
- Loss of previously attained cognitive or language
milestones confirmed by standardized testing
11Clinical motor dysfunction
- Progressive on 2 individual examinations
separated by at least 1 month - Loss or significant deterioration of motor skills
in any two of the following criteria - diffuse and symmetric loss or deterioration of
power that is not the results of systemic,
nutritional or metabolic compilation - diffuse and symmetric abnormalities of tone
- diffuse and symmetrical increases in tendon
reflexes
12In resource poor countries
- Impaired brain growth
- Infants with HC lt 5th percentile
- Children lt3 yrs crossing 2 major percentiles from
baseline HC - Children HC falling below lt 5th percentile
- Children with serial neuroimagining studies
showing loss of brain parenchyma - Neurodevelopment decline
- Child lt 3 years Fall of 2 SD on a standardized
non-screening developmental assessment - Child gt 3 years Fall of at least 1SD on
standardised test of intelligence - Any age Loss of previously attained cognitive or
language milestones confirmed by standardized
testing - Motor impairment
- Loss or significant deterioration of motor skills
13In the absence of another cause
- Many causes of progressive encephalopathy in
children - CNS infections
- Non-infectious causes
- Diagnosis needs
- Neuroimagining
- Blood tests
- extensive
- expensive
14Other causes of progressive encephalopathy
- Aminoacidurias
- 1. Homocystinuria
- 2. Maple syrup urine disease
- a. Intermediate form
- b. Thiamine-responsive form
- 3. Phenylketonuria
- Lysosomal Enzyme Disorders
- 1. Glycoprotein degradation disorders
- a. Mannosidosis type I
- b. Fucosidosis types I and II
- c. Sialidosis type II (infantile form)
- 2. Mucolipidoses
- a. Type II (1-cell)
- b. Type IV
- 3. Mucopolysaccharidoses
- a. Type I (Hurler)
- b. Type II (Sanfilippo)
- 4. Sphingolipidoses
- Hypothyroidism
- Mitochondrial Disorders
- 1. Mitochondrial myopathy, encephalopathy,
lactic acidosis, stroke - 2. Progressive infantile poliodystophy (Alper).
- 3. Subacute necrotizing encephalomyelopathy
- (Leigh)
- 4. Trichopoliodystrophy (Menkes)
- Neurocutaneous Syndromes
- 1. Chediak-Higashi syndrome
- 2. Neurofibromatosis
- 3. Tuberous sclerosis
- Other Genetic Disorders of Gray Matter
- 1. Infantile ceroid lipofuscinosis (Santavuori)
- 2. Infantile neuroaxonal dystrophy
- 3. Lesch-Nyhan disease
-
15Opportunistic CNS infections
- Fungal
- Candida
- Cryptococcus
- Aspergillus sp
- Actinomyces
- Histoplasma
- Bacterial
- Pseudomonas sp
- Streptococcus sp.
- Toxoplasmosis
- Viral
- CMV
- Varicella Zoster
- Herpes simplex
- papovavirus
- Ebstein Barr
- Mycobacterium
- M. tuberculosis
- M. avium intracellulare
16Major Domains
- Impairment of brain growth
- Decline of cognitive function
- Clinical motor dysfunction
17In Kilifi Kenya
- Kilifi community
- Second poorest area in Kenya
- Underweight
- (WAZ lt -2) 24
- Alone 5.7
- Underweight and stunted 19.7
18Head circumferences in Kilifi community
19Prevalence of Microcephaly and Macrocephaly in
Community children
20Major Domains
- Impairment of brain growth
- Decline of neurodevelopment function
- Clinical motor dysfunction
21Considerations.
- High prevalence of neurodevelopment impairment in
communities - In the age group in which most children with
vertical HIV transmission manifest lt 3 years - Motor function most easily assessed
- Lack of cultural appropriate tests for cognitive
and language tests
22Prevalence of Neurocognitive Impairment
23Motor development in 6 centres
WHO Acta Pædiatrica, 2006 Suppl 450 66/75
24Interobserver variation in assessment of motor
signs
Thomas et al Dev Med Child Neurol 2001 43 97-102
25Major Domains
- Impairment of brain growth
- Decline of cognitive function
- Clinical motor dysfunction
26Clinical motor dysfunction
- Loss or significant deterioration of motor skills
in any two of the following criteria - diffuse and symmetric loss or deterioration of
power that is not the results of - systemic,
- nutritional or
- metabolic compilation
- diffuse and symmetric abnormalities of tone
- diffuse and symmetrical increases in tendon
reflexes - Interobserver variation
27So what do we need to do.
- Study a cohort of HIV ve children in sub-Saharan
African with encephalopathy - Identify CNS infections
- Obtain Neuroimagining
- Investigate possible metabolic causes
- Identify neurodevelopmental skills that can be
applied across SSA in the age range 6 48 months - Develop cultural and language appropriate
assessments of neurodevelopment - Standardised on large populations
- Improve neurological examination
- Training videos
28In the meantime.
- So can we define HIV encephalopathy in SSA?
- Child who is HIV positive
- Lack of growth in head circumference
- Serial measurements at least 3 months apart
- ? lt 2 years
- Neurodevelopmental milestones
- Loss of skills, particularly motor
- Lack of acquisition of neurodevelopment skills
- Diffuse symmetrical hyperreflexia
- Lumbar puncture to exclude CNS infections
29Acknowledgements
- Kilifi, Kenya
- Sadik Mithwani
- Penny Holding
- Amina Abubakar
- Jay Berkley
- New York University School and Family Care
Clinic, Coast Province General Hospital, Mombasa,
Kenya - Shaffiq Essajee
30Thank you
31Laboratory Evaluations for Children With Acute
CNS Manifestations
- Blood
- Complete blood count
- Blood culture
- Electrolytes
- Toxicology screen
- Toxoplasmosis antibody
- Cryptococcal Ag culture
- Lumbar puncture
- Opening pressure
- Cell count, Gram stain
- Protein, Glucose
- Bacterial culture
- Cryptococcal antigen and culture
- PCR for EBV, CMV, VZV and HSV
- Viral, fungal and mycobacterial cultures
- VDRL