Tamrat AbebeJemal Aman2026-06-222026-06-222025https://etd.aau.edu.et/handle/123456789/8285Background: Meningitis poses a major public health challenge in sub-Saharan Africa, often triggering devastating epidemics. Although it can affect individuals of all ages, infants, children, and immunocompromised persons are at the greatest risk. In Ethiopia, meningitis continues to be a significant public health concern due to its potential for outbreaks, high mortality rates, and the considerable burden it places on the healthcare system. Objective: This study was aimed to assess the prevalence of etiologic agents causing meningitis and to evaluate immune correlates of risk among clinically suspected meningitis cases in Ethiopia. Methods: An institutional-based cross-sectional study was conducted from August 2023 to June 2024 at ALERT Comprehensive Specialized Hospital and Hawassa University Comprehensive Specialized Hospitals. A total of 201 clinically suspected meningitis cases of all age groups (except neonates) were enrolled. Cerebrospinal fluid (CSF) samples were analyzed using conventional culture, microscopy, and Conventional multiplex PCR to identify bacterial and viral pathogens. Immune correlates of risk including CD4+ T-cell counts and plasma complement levels (C5, C5a, C9, Factor D, MBL, Factor I, Properdin)- were compared among cases with bacterial meningitis, viral meningitis cases and healthy individuals. Univariate and multivariate logistic regression analyses were performed to identify significant associations. Results: The overall prevalence of bacterial meningitis detected by classical CSF culture was 5.5% (n = 11), with Klebsiella pneumoniae 3/11(1.5%) being the most frequently isolated organism. In contrast, multiplex PCR identified a substantially higher prevalence of bacterial meningitis at 36.8% (n = 74), with Escherichia coli 30/74(14.9%), Streptococcus pneumoniae 15/74(7.5%), and Neisseria meningitidis 11/74(5.5%) as the predominant pathogens. Klebsiella pneumoniae 9/74(4.5%), Streptococcus agalactiae 4/74(2%), and Listeria monocytogenes 2/74(1%) were also rarely detected. Antimicrobial resistance was alarmingly high, with 72.7% of bacterial isolates exhibiting resistance to three or more antibiotics. The overall prevalence of viral meningitis was 34.3% (n = 69), with Human Enteroviruses (28.9%) representing the most common viral etiology. Overall 65% [13/20] of patients with viral meningitis have CD4 deficiency [<200cells/mm3]. 54% [27/50] of patient with bacterial meningitis have Properdin deficiency followed by 52% [26/50] C5- Deficiency and 46% [23/50] C9- deficiency. Analysis of immune correlates revealed that deficiencies in complement components C5 (AOR = 2.50, 95% CI: 1.60–3.90, p < 0.001), C9 (AOR = 3.09, 95% CI: 1.31 7.30, p = 0.007), and Properdin (AOR = 1.80, 95% CI: 1.20–2.70, p = 0.003) were significantly associated with an increased risk of bacterial meningitis. For viral meningitis, low CD4+ T-cell levels were significantly associated with increased risk (AOR = 2.59, 95% CI: 1.60–3.90, p = 0.035). Conclusion and recommendation: In conclusion, our study confirms a significant burden of bacterial and viral meningitis in our study settings, disproportionately affecting young children. Our findings highlight specific immune correlates of risk for meningitis: deficiencies in terminal complement components (C5, C9, and Properdin) significantly increase susceptibility to bacterial meningitis, whereas low CD4+ T-cell levels are associated with a higher risk of viral meningitis. These findings highlight the urgent need for enhanced diagnostic capabilities, expanded vaccination programs, stringent antibiotic stewardship, and the implementation of immune profiling for better patient management in Ethiopia. Future research should track long-term outcomes and evaluate intervention effectiveness.enMeningitis bacterial meningitis viral meningitis immune correlates complement components CD4 counts Ethiopia.Thesis