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Etiology, Disease Severity and Diagnostic Challenges of Bacterial Meningitis during Non-epidemic Seasons in Ethiopia

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dc.contributor.advisor Petros, Beyene (Professor)
dc.contributor.author Mihret, Wude
dc.date.accessioned 2018-07-19T08:14:36Z
dc.date.available 2018-07-19T08:14:36Z
dc.date.issued 2017-06
dc.identifier.uri http://localhost:80/xmlui/handle/123456789/9423
dc.description.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. en_US
dc.language.iso en en_US
dc.publisher Addis Ababa Universty en_US
dc.subject Bacterial Meningitis en_US
dc.title Etiology, Disease Severity and Diagnostic Challenges of Bacterial Meningitis during Non-epidemic Seasons in Ethiopia en_US
dc.type Thesis en_US

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