Cytokine profile in patients with acute bacterial meningitis.

BACKGROUND: Bacterial meningitis is a life-threatening disease with high mortality and common long-term sequelae. The inflammatory response in the subarachnoid space, modulated by different cytokines, plays a major role in the pathogenesis of acute central nervous system infections. We aimed to examine correlations of interleukin (IL)-6, IL-8, IL-10, IL-12(p40), and tumor necrosis factor (TNF)-α levels with disease severity, complications, and outcome in patients with acute bacterial meningitis. METHODS: The study involved 30 patients with bacterial meningitis/meningoencephalitis admitted to the University Hospital St. George, Plovdiv over a period of 4 years. Patients were selected based on clinical presentation and laboratory abnormalities, consistent with a neuroinfection. Enzyme-linked immunosorbent assay was used to measure the studied cytokines in both cerebrospinal fluid (CSF) and serum in parallel. For microbiological diagnosis multiplex, polymerase chain reaction, and CSF culture were used. RESULTS: In patients with acute bacterial meningitis CSF levels of IL-6, IL-8, IL-10, and TNF-α are significantly increased than in serum. CSF TNF-α, CSF IL-8, and CSF IL-10 had a moderate negative correlation to CSF glucose. It was found that serum IL-8 is significantly elevated in patients who experienced neurological complications, have severe clinical course, and in deceased patients. CSF IL-10 is increased only in patients with severe acute bacterial meningitis. CONCLUSION: Among patients with acute bacterial meningitis serum IL-8 could delineate these with increased risk of neurological complications, severe clinical course, and fatal outcome. Serum IL-8 and CSF IL-10 could be used as indicators of disease severity.

Combined testing of cerebrospinal fluid IL-12 (p40) and serum C-reactive protein as a possible discriminator of acute bacterial neuroinfections.

INTRODUCTION: Central nervous system infections (CNS) are life-threatening diseases, with meningitis being the most common. Viral infections are usually self-limiting diseases but bacterial pathogens are associated with higher mortality rates and persistent neurological sequelae. We aimed to study the role of IL-6, IL-8, IL-10, IL-12(p40), TNF-α cytokines, classical cerebrospinal fluid (CSF) parameters, and serum C-reactive protein levels (CRP) for discriminating bacterial from viral central nervous system infections. MATERIAL AND METHODS: This prospective study included 80 patients with clinical signs and abnormal cerebrospinal fluid laboratory findings typical for neuroinfection admitted to St. George University Hospital-Plovdiv. Routine methods such as direct microscopy, culturing and identification were used for microbiological analysis as well as latex-agglutination test and multiplex PCR. Cytokines' concentrations were measured by ELISA. CRP and CSF parameters were collected from the patients' medical records. RESULTS: We observed the highest discriminatory power among cytokines for cerebrospinal IL-12(p40) (AUC = 0.925; p = 0.000). CSF protein levels were the best predictor for bacterial neuroinfection (AUC = 0.973; p = 0.000). The AUC for the serum CRP as a stand-alone biomarker was estimated to be 0.943. The discriminatory power can be increased up to 0.995 (p = 0.000) when combining cerebrospinal fluid IL-12(p40) and serum CRP, with an optimal cut-off value of 144 (Sensitivity 100%; Specificity 90.9%). CONCLUSION: The combined testing of CSF IL-12(p40) and serum CRP is associated with the highest diagnostic accuracy.

Clinical aspects of hantavirus infections in Bulgaria.

BACKGROUND: Hantaviruses cause two distinct human diseases: hemorrhagic fever with renal syndrome (HFRS) in Asia and Europe and hantavirus pulmonary syndrome (HPS) in America. In Europe, mainly Puumala, Dobrava and Seoul viruses cause HFRS. A total of 23 cases of HFRS were detected in Bulgaria over a 2­year period 2013-2014. The aim of the study was to present epidemiology, clinical manifestations and laboratory findings of these patients. METHODS: Patients with HFRS were diagnosed using PCR, ELISA and immunoblotting tests. RESULTS: Dobrava-Belgrade virus (DOBV) was revealed as etiological agent in 16 (69.6%) patients and Puumala virus (PUUV) in 7 (30.4%) patients. All 23 patients were men aged 22-66 years of which 6 (26.1%) patients originated from regions in northern and western Bulgaria previously thought to be non-endemic. Patients with HFRS, despite the infecting hantavirus, manifested acute renal failure, asthenia and less pronounced hemorrhagic syndrome. Patients with DOBV infection were much more likely to present with arthromyalgia, severe headache, severe to moderately severe asthenoadynamia, abdominal pain, vomiting, hypotension, nervous system disorders as well as kidney enlargement, leucopenia and higher levels of blood creatinine, requiring hemodialysis procedures more often and for a longer period of time than patients with PUUV infection. CONCLUSIONS: The present report describes for the first time comparative analysis of epidemiological features, clinical manifestations and laboratory findings of DOBV and PUUV infections in Bulgaria.

Aseptic meningitis outbreak caused by echovirus 30 in two regions in Bulgaria, May-August 2012.

An aseptic meningitis outbreak emerged in two regions in Bulgaria in 2012 and echovirus 30 (E30) was established as the aetiological agent by cell culture isolation, serological test, and molecular-based techniques. A total of 157 patients with aseptic meningitis were investigated, of which 117 were confirmed as having E30-associated disease. Molecular analysis of 12 E30 isolates revealed 99-100% nucleotide and amino-acid identity between them and a close correlation with a Greek strain involved in an E30 outbreak in 2012. Children aged 5-14 years were mainly affected, which could reflect the absence of E30 epidemics in Bulgaria for a period of 11 years. The first case with E30 isolation (a 2-year-old patient from Plovdiv) was notified at the end of April 2012. This was most likely the index case, from which the spread of the virus started, causing sporadic cases first, which later led to an aseptic meningitis outbreak facilitated by person-to-person viral transmission.