Etiology, Disease Severity and Diagnostic Challenges of Bacterial Meningitis during Non-epidemic Seasons in Ethiopia
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Date
2017-06
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Addis Ababa Universty
Abstract
Bacterial meningitis (BM) is a severe infectious disease of the nervous system that needs
urgent medical attention. Ethiopia, a country located at the eastern end of the “meningitis
belt”, is frequently affected by meningitis epidemics. Studies have rarely focused on nonepidemic
season strains of BM and use of less sensitive diagnostic tools have impeded
characterization of its causative organisms. A prospective case-based study was launched
from 2012-2013 on 139 patients clinically diagnosed with BM. The objective of the study
was to obtain recent data on the frequent etiologies of BM, diagnostic challenges and
disease severity in Ethiopia during non-epidemic seasons. Cerebrospinal fluid (CSF)
samples taken from the study participants were subjected to bacterial culture, molecular
and immunological lab analyses while sera were evaluated by immunological assays.
The patient’s ages were varying from 2 days to 78 years old and > 50% of the total study
population were in ≤ 12 years old age category. Younger age groups than olders, males
than females faced higher level of BM induced disease severity (i.e. death or sequelae).
Bacterial culture detection test performed at the research lab recovered 14 (10.1%) live
isolates out of 139 CSFs. These comprises of N. meningitidis (n = 5, serogroups A (n =
4) + W-135 (n = 1)), S. pneumoniae (n= 8), and H. influenzae (n =1) from the CSFs of the
patients. Real time PCR (RT-PCR) detected a total of 46 (33.1%) etiologic agents of BM
composing N. meningitidis in 27/46 (58.7%), genogroups A (11/27, 40.7%), W-135
(7/27, 26%), C (1/27, 3.7%), X (1/27, 3.7%) and non-groupable (7/27, 26%),
S.pneumoniae in 18/46 (39.1%) and H. influenzae in 1/46 (2.2%). Hospital lab versus
research lab results for 50 patients whose clinical lab data were found were compared and the hospital lab results showed less specificity for N. meningitidis (91% versus 100%) and
S. pneumoniae (95% versus 100%), decreased PPV for N. meningitidis (50% versus
100%) and S. pneumoniae (33% versus 100%), decreased NPV for N. meningitidis (66%
versus 68%) and S. pneumoniae (85% versus 93%) respectively. Levels of IL-4, IL-8, IL-
12/p70, INF-g, MCP-1, MIP-1α, MIP-1β, RANTES, TRAIL and MMP9 in the CSF were
significantly elevated in BM caused by S. pneumoniae compared to that of
N.meningitidis, consistent with a worsened outcome by the former. Significantly different
(P < 0.05) levles of median endotoxin activities (measured by Limulus Amoebocyte
Lysate/LAL) were detected among N. meningitidis positive patients with different clinical
conditions. Streptococcus pneumoniae positive patients who died (n = 3) had significantly
high (P < 0.05) levels of MMP9 and IL-1b compared to the survived ones. Fifty patients
out of 139 were reported to develop sequelae in age groups £4 (epilepsy, n = 1), £ 4
(raised intracranial pressure, n = 1), ³ 40 (quadriparesis, n = 1), 20-29 (confusion in age
group, n = 20-29), while seizure was reported in age groups £4 (n = 22), 5-12 (n = 7), 13-
19 (n = 4), 20-29 (n = 7) and ³ 40 (n = 4). Seventeen patients out of the 48 with
specifically reported sequelae were RT-PCR confirmed positive for BM etiologic agents.
Types of sequelae were not specifically reported for two patients. Three N. meningitidis
and 6 S. pneumoniae positive patients who experienced sequelae showed increased trends
of IL-1b, IL-6 and IL-1ra compared to those with no sequelae and negative controls.
Affordable, multivalent meningitis vaccines composed of serogroups A, C, W-135 and X
are urgently needed for use in Ethiopia and possibly in all countries within the African
meningitis belt.
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Keywords
Bacterial Meningitis