Etiology Disease Severity And Diagnostic Challenges Of Bacterial Meningitis During Non-epidemic Seasons In Ethiopia

Bacterial meningitis (BM) is a severe infectious disease of the nervous system that needsrnurgent medical attention. Ethiopia, a country located at the eastern end of the “meningitisrnbelt”, is frequently affected by meningitis epidemics. Studies have rarely focused on nonepidemicrnseason strains of BM and use of less sensitive diagnostic tools have impededrncharacterization of its causative organisms. A prospective case-based study was launchedrnfrom 2012-2013 on 139 patients clinically diagnosed with BM. The objective of the studyrnwas to obtain recent data on the frequent etiologies of BM, diagnostic challenges andrndisease severity in Ethiopia during non-epidemic seasons. Cerebrospinal fluid (CSF)rnsamples taken from the study participants were subjected to bacterial culture, molecularrnand immunological lab analyses while sera were evaluated by immunological assays.rnThe patient’s ages were varying from 2 days to 78 years old and > 50% of the total studyrnpopulation were in ≤ 12 years old age category. Younger age groups than olders, malesrnthan females faced higher level of BM induced disease severity (i.e. death or sequelae).rnBacterial culture detection test performed at the research lab recovered 14 (10.1%) livernisolates out of 139 CSFs. These comprises of N. meningitidis (n = 5, serogroups A (n =rn4) + W-135 (n = 1)), S. pneumoniae (n= 8), and H. influenzae (n =1) from the CSFs of thernpatients. Real time PCR (RT-PCR) detected a total of 46 (33.1%) etiologic agents of BMrncomposing N. meningitidis in 27/46 (58.7%), genogroups A (11/27, 40.7%), W-135rn(7/27, 26%), C (1/27, 3.7%), X (1/27, 3.7%) and non-groupable (7/27, 26%),rnS.pneumoniae in 18/46 (39.1%) and H. influenzae in 1/46 (2.2%). Hospital lab versusrnresearch 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%) andrnS. pneumoniae (95% versus 100%), decreased PPV for N. meningitidis (50% versusrn100%) and S. pneumoniae (33% versus 100%), decreased NPV for N. meningitidis (66%rnversus 68%) and S. pneumoniae (85% versus 93%) respectively. Levels of IL-4, IL-8, IL-rn12/p70, INF-g, MCP-1, MIP-1α, MIP-1β, RANTES, TRAIL and MMP9 in the CSF werernsignificantly elevated in BM caused by S. pneumoniae compared to that ofrnN.meningitidis, consistent with a worsened outcome by the former. Significantly differentrn(P < 0.05) levles of median endotoxin activities (measured by Limulus AmoebocyternLysate/LAL) were detected among N. meningitidis positive patients with different clinicalrnconditions. Streptococcus pneumoniae positive patients who died (n = 3) had significantlyrnhigh (P < 0.05) levels of MMP9 and IL-1b compared to the survived ones. Fifty patientsrnout of 139 were reported to develop sequelae in age groups £4 (epilepsy, n = 1), £ 4rn(raised intracranial pressure, n = 1), ³ 40 (quadriparesis, n = 1), 20-29 (confusion in agerngroup, n = 20-29), while seizure was reported in age groups £4 (n = 22), 5-12 (n = 7), 13-rn19 (n = 4), 20-29 (n = 7) and ³ 40 (n = 4). Seventeen patients out of the 48 withrnspecifically reported sequelae were RT-PCR confirmed positive for BM etiologic agents.rnTypes of sequelae were not specifically reported for two patients. Three N. meningitidisrnand 6 S. pneumoniae positive patients who experienced sequelae showed increased trendsrnof IL-1b, IL-6 and IL-1ra compared to those with no sequelae and negative controls.rnAffordable, multivalent meningitis vaccines composed of serogroups A, C, W-135 and Xrnare urgently needed for use in Ethiopia and possibly in all countries within the Africanrnmeningitis belt.

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