The effect of HIV infection on acute bacterial meningitis in children

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The effect of HIV infection on acute bacterial
meningitis in children

• Elizabeth Molyneux
• Department of Paediatrics
• College of Medicine
• Malawi

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Bacterial meningitis

• Every year
• 125,000 children die from BM
• 96 occur in less developed world
• where case fatality rate 18 -47
• where sequelae 25-50

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Global AIDS 2002

• 2.2 MILLION CHILDREN lt15 YRS HAVE AIDS/HIV
• 90 live in sub-Saharan Africa
• 640,000 new infections in children in 2004
• 510,000 child deaths due to AIDS in 2004
• 12 MILLION ORPHANS IN AFRICA

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IN MALAWI 2002

• 44 OF POPULATION lt15YRS
• 8.8 POPULATION WITH AIDS 900,000
• 14.4 of 15-49 yrs
• 16 30 of pregnant women (10 MTCTM)
• of the total
  
• 6 0-4yrs
• 3 5-9yrs
• 86,000 deaths per annum
• 700,000 vulnerable children
• ORPHANS 850,000

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Positive CSFs in 2004 498 (19.7)
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Paediatric Meningitis Bacterial Pathogens
1996-May 2001Queen Elizabeth Hospital,
Blantyre, Malawi
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Trends in Hi Sp paediatric (lt5y) meningitis
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Background
Bacterial meningitis - mortality 12-50 in
developing countries - survivors
30 left with sequelae HIV seropositivity is
increasing prevalence study QECH, 18.9 HIV
admissions HIV seropositivity increased
infections ? HIV status alters course and
outcome of ABM
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Background - Overall HIV prevalence in
QECH Rogerson et al Trans Roy Soc Trop MH 2004
98544-552
187/991 18.9 53/166 lt 6 months old 32
Malnutrition 40 Lower respiratory
infection 29 Sepsis 28 Malaria 11
Surgical problems 11 Mortality HIV
infected 30 HIV uninfected 8.9
40 of all inpatient deaths in HIV infected
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Background

• In Blantyre - HIV infection rates in the hospital
• 62 of marasmus
• 22 of kwashiorkor
• 71 of TB
• 34 bacterial meningitis
• In RSA Madhi et al
• 64.5 in S pneumoniae pneumonia /- meningitis

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Study details
QECH July 1997 -Sept
2000 Double blind randomised placebo controlled
study of adjuvant steroid therapy in
ABM Definition of ABM CSF gt100 WBC/cmm, and/or
Gram stain and/or culture positive HIV testing
after precounselling and consent. If Elisa test
positive repeated x 1. If results discordant
repeated x 2. If child lt15months confirmed by PCR
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General data
Number of patients entered 598 HIV tested
459 (139 not tested, 100 before permission to
proceed 33 inadvertently missed, 5 refused, 1 no
guardian HIV 157 (34)
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CLINICAL FINDINGS OVERALL ()
N 597 ?
HIV seropositivity HIV HIV -
Number of children 157 302 Median
Age(months) 12 12 Male Female 4753 60
40 Median Wgt for Age 73 81 Median
fever (days) 3 3
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CLINICAL FINDINGS OVERALL ()
N 597 ?
HIV seropositivity HIV HIV
Number of children 157 302 Median
Age(months) 12 12 Male Female 4753 60
40 Median Wgt for Age 73 81 Median
fever (days) 3 3 History of
seizures 94 (61) 132 (44) P0.001 Not
sucking 90 (57) 128 (42) P0.03
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CLINICAL FINDINGS OVERALL ()
N 597 ?
HIV seropositivity HIV HIV -
Number of children 157 302 Median
Age(months) 12 12 Male Female 4753 6040
Median Wgt for Age 73 81 Median fever
(days) 3 3 History of
seizures 94(61) 132(44) P0.001 Not
sucking 90 (57) 128 (42) P0.03 Prior
antibiotics 73 (47) 101 (47) Ear
infection 32 (21) 24 (8) P0.0002 Focus of
infection 85 (64) 57 (19) P0.0001 Malaria
parasites (13.4) (16.4)
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HIV seropositivity HIV HIV - Number of
children 157 302 Skin rash 18 (11) 11
(7) P0.02 Generalised LN 32 (21) 12
(4) P0.00001 Hepatomegaly 65 (41) 51
(17) P0.00001 Splenomegaly 43 (27) 59
(19.5) P0.07 Shock 33 (11) 12
(2.5) P0.00001 Coma Score lt2 67 (43) 111
(37) P0.26 Mean Bd glucose mmol/L 5.6 5.9 M
edian Temp 0C 38 38.4 Median Haematocrit
29 30
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Causative agents HIV HIV_
H. Influenzae 32 (20) 98 (32) P 0.009
S.Pneumonae 92 (52) 98 (32) P0.0001
N.Meningitides 4 (2) 32 (10.5) P
0.004 Salmonellae spp 10 (6) 14 (5)
P0.56 No growth 14 (9) 50 (16.5)
P0.035 Other 5 (3) 10 (3)
P0.8 ?includes 16 cases
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Progress in hospital
HIV seropositivity HIV HIV- No of
children 157 302 Median Time (hrs) for
33 24 Temp to lt 37 C 6-264 1-456 No
requiring anticonvulsant 74 (47) 119
(39) USS of head done 28 82 Abnormal
findings 13 (46) 34 (41) No
requiring 2nd antibiotic 43 (27) 114
(38) Subdural/abscess tapped 3 ( 2) 6
( 2) Blood transfusion 3 ( 2) 6 (
2)
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Lab Results in HIV and HIV - patients
Blood glucose, malaria parasitaemia peripheral
WCC similar CSF WCC mean 2918 0-100,000 in
HIV CSF WCC mean 5267 0-100,000 in
HIV- p NS
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Overall Outcome
HIV serostatus HIV HIV- Number of children
157 302 Died in Hospital 88 (56)
89 (29) Died after discharge of
meningitis related problem 6 (3)
14 (4.6) Died after discharge of non meningitis
problem 8 (5) 6
(2) Survivors with full recovery 27 (17) 92
(30) Total with sequelae 30 (19) 88
(29) All hearing loss 21(37) of surv 55
(30.5) All neuro sequelae 26(46) of surv
71 (39)
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HEARING RESULTS in SURVIVORS
HIV STATUS HIV HIV- Number of
survivors 57 180 Hearing normal 24 (42) 103
(57) Bilateral loss 12 (57) 35
(64) Bilateral reduction 6 (10.5) 7
(13) Unilateral loss 1 (2) 14
(25) Conductive loss 6 10 Inconclusive
test 10 19 Not tested 3 14
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Role of HIV status in steroid treated and
placebo groups
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Affect of HIV status on bacterial sensitivities

• No overall difference in bacterial resistance
• except of pneumococci from HIV
• (less resistant to chloramphenicol than HIV-
• (3 v 16 p0.006)
• HIV- 15 H influenzae (15/99)
• 13 (13/97) S. pneumoniae fully sensitive.
• HIV 12.5 (4/32) H. influenzae
• 4.4 (4/89) S pneumoniae fully sensitive.

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CONCLUSIONS

• HIV present with more foci of infection
  (54v19)
• more shock (21v 4)
• Otherwise no sicker on arrival.
• HIV took longer to become afebrile than HIV- but
  progress similar.
• HIV more deaths (65v36)
• HIV less full recovery (15v30)

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CONCLUSIONS

• Sequelae similar
• Hearing loss less common in HIV
• 47.2v 66.3 p 0.029
• Steroids ? increased CFR in HIV -
• but not sequelae in either HIV or
• Recurrence not due to drug resistant
• (occurred after 2-77/52).
• Recurrence much more common in HIV

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Madhi et al 2003 South Africa Severe S
pneumoniae infection 41.7 (26.5-65.6) greater in
HIV Gwanzura et al 2003 Zimbabwe S. Pneumoniae
infections (BC and CSF) 75 HIV Nathoo et al
1998 Zimbabwe NTS (BC) 13.2 in HIV compared
with 3.6 in HIV ve
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• Madhi et al 2000 South Africa
• S pneumoniae resistance to penicillin
• 46 in HIV 28 in HIV
• CoT
• 19 HIV v 4.5 HIV
• S Aureus
• 60 methicillin resistant in HIV
• E.Coli
• 85.7 resistant to CoT
• Gwanzura et al 2003 Zimbabwe
• S pneumoniae resistance to penicillin
• 16 in HIV 6 in HIV -

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• Scott JA et al 1998 Kenya
• Serotype 1 S pneumoniae caused 44 infections in
  HIV-
• 98 sensitive to penicillin
• caused 5 infections in HIV
• Zar et al 2003 South Africa
• Use of CoT
• S aureus carriage increased to
• 22 HIV- and 44 in HIV

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Increasing Hib antibiotic resistance 1996-June
2002Queen Elizabeth Hospital, Blantyre, Malawi
Wellcome Trust Laboratory QEH, October 2004
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