Olga Dulovic

The microbiological diagnosis of tuberculous meningitis: results of Haydarpasa-1 study

We aimed to provide data on the diagnosis of tuberculous meningitis (TBM) in this largest case series ever reported. The Haydarpasa-1 study involved patients with microbiologically confirmed TBM in Albania, Croatia, Denmark, Egypt, France, Hungary, Iraq, Italy, Macedonia, Romania, Serbia, Slovenia, Syria and Turkey between 2000 and 2012. A positive culture, PCR or Ehrlich-Ziehl-Neelsen staining (EZNs) from the cerebrospinal fluid (CSF) was mandatory for inclusion of meningitis patients. A total of 506 TBM patients were included. The sensitivities of the tests were as follows: interferon-γ release assay (Quantiferon TB gold in tube) 90.2%, automated culture systems (ACS) 81.8%, Löwenstein Jensen medium (L-J) 72.7%, adenosine deaminase (ADA) 29.9% and EZNs 27.3%. CSF-ACS was superior to CSF L-J culture and CSF-PCR (p <0.05 for both). Accordingly, CSF L-J culture was superior to CSF-PCR (p <0.05). Combination of L-J and ACS was superior to using these tests alone (p <0.05). There were poor and inverse agreements between EZNs and L-J culture (κ = -0.189); ACS and L-J culture (κ = -0.172) (p <0.05 for both). Fair and inverse agreement was detected for CSF-ADA and CSF-PCR (κ = -0.299, p <0.05). Diagnostic accuracy of TBM was increased when both ACS and L-J cultures were used together. Non-culture tests contributed to TBM diagnosis to a degree. However, due to the delays in the diagnosis with any of the cultures, combined use of non-culture tests appears to contribute early diagnosis. Hence, the diagnostic approach to TBM should be individualized according to the technical capacities of medical institutions particularly in those with poor resources.

Varicella complications: Is it time to consider a routine varicella vaccination?

BACKGROUND/AIM Varicella is a common and benign disease of childhood. Complications are rare, but in some patients, even without risk factors, severe, life treathening complications could be seen. The aim of this study was to establish the type and frequency of varicella complications among hospitalised patients over an 8-year period. METHODS This retrospective analysis included medical charts of the patients hospitalised in the Infectious Disease Clinic, Belgrade, Serbia, from 2001-2008 (4.85% of all registered patients with varicella in Belgrade, 2001-2008). Among hospitalised patients dermografic characteristics were analysed: hospitalisation lenght, presence and type of complications, presence of immunocompromising conditions and outcome of the disease. The diagnosis of varicella was made on clinical grounds, and in persons >40 years, with negative epidemiological data of contacts, serological confirmation (ELISA VZV IgM/IgG BioRad) and avidity of IgG antibodies were done to exclude the possibility of disseminated herpes zoster. RESULTS A total of 474 patient were hospitalised over an 8-year period. The age of patients was from 5 months to 75 years (mean 22.4 +/- 16.1, median 23.5 years). The majority of patients were adults (n=279; 58.9%) and 195 (41.1%) patients were < or =15 years old. Complications were found in 321/474 (67.7%) patients. The registered complications were: varicella pneumonia (n=198; 41.38%), bacterial skin infections (n=40; 8.4%), cerebelitis (n=28; 5.9%), bacterial respiratory infection (n=21; 4.4%), viral meningitis (n=10; 2.31%), encephalitis (n=9; 1.9%), thrombocytopenia (n=2; 0.4%); 11 (2.3%) patients had more than one complication, among them were sepsis, myopericarditis and retinal hemorrhages. When complications were analysed according to the age, there were no statistical significance, but when type of complication was analysed statistical significance was found (p < 0.05). In adults, pneumonia was the most common complication: 173/279 (62%), followed by skin infections (2.9%), bacterial respiratory infections (2.2%), and more than one complication (2.3%). Pneumonia was more common in adults than in children (7:1). In children skin infections were the most common complications (16.4%), followed by cerebelitis (13.3%), viral pneumonia (12.8%), bacterial respiratory infections (7.7%), encephalitis (3.6%), and more than one complication (4.1%). Neuroinfections were more common in children than in adults (6:1), as well as bacterial skin infections (4:1). Two patients died (0.4%). CONCLUSION There was no difference in the incidence of varicella complication in children and adults, but the type of complication differed. In children the most common complications were skin and neurological infections, while in adults it was varicella pneumonia. These data provide a baseline for estimating the burden of varicella in Belgrade and support the inclusion of varicella vaccine in childhood immunisation program in Serbia.

Hydrocephalus and vasculitis delay therapeutic responses in tuberculous meninigitis: Results of Haydarpasa-III study

AIMS There is no report on the factors affecting the resolution of symptoms related to meningitis during treatment of tuberculous meningitis (TBM). Thus, we examined the factors associated with early therapeutic responses. MATERIALS AND METHODS This multicenter study included 507 patients with microbiologically confirmed TBM. However, 94 patients eligible for the analysis were included in this study from 24 centers. Six out of 94 patients died and the statistical analysis was performed with 88 survivors. Early and late responder groups were compared in the statistical analysis. P < 0.05 were considered to show a significant difference. RESULTS In the multivariate analysis, the presence of vasculitis (P = 0.029, OR = 10.491 [95% CI, 1.27-86.83]) was found to be significantly associated with a delayed fever response whereas hydrocephalus was associated with altered mental status for >9 days duration (P = 0.005, OR = 5.740 [95% CI, 1.68-19.57]). According to linear regression analysis, fever was significantly persisting (>7 days) in the presence of vasculitis (17.5 vs. 7, P< 0.001) and hydrocephalus (11 vs. 7, P = 0.029). Hydrocephalus was significantly associated with persisting headache (21 vs. 12, P = 0.025), delayed recovery of consciousness (19.5 vs. 7, P = 0.001), and a delay in complete recovery (21 vs. 14, P = 0.007) in the linear regression analysis. Following institution of treatment, the complaints seemed to disappear in up to 2 weeks among TBM survivors. CONCLUSIONS In the absence of hydrocephalus or vasculitis, one week of anti-tuberculosis treatment seems to be adequate for the resolution of TBM symptoms. Hydrocephalus and vasculitis delay the resolution of TBM symptoms in response to antimycobacterial treatment.

Molecular characterization of vancomycin-resistant enterococci in Serbia: intensive care unit as the source.

The purpose of this study was to evaluate the molecular relatedness of clinical isolates of vancomycin-resistant enterococci (VRE) collected from patients of the Clinic for Infectious and Tropical Diseases in Belgrade. Among 40 isolates available for the investigation, 36 were identified as Enterococcus faecium, whereas 2 were Enterococcus faecalis and Enterococcus raffinosus, respectively. Pulsed-field gel electrophoresis (PFGE) typing revealed 21 strain types, comprising 7 clusters which contained at least two isolates and 14 unique PFGE patterns. Although we searched for pathogenicity factor genes (gelE, cylB, asa1, efaAfs, esp, cpd, cob) in representatives of all macro-restriction patterns, they have been confirmed in only one clone of E. faecalis. Genes esp and hyl, commonly found in E. faecium, were yilded in 10 macro-restriction patterns of this species, and their presence could not be ascribed to clonally related strains (p = 0.05). All VRE isolates were multiresistant and positive for vanA gene. Twenty strains of VRE and 6 clusters obtained from Intensive care unit (ICU) are proof of intensive transmission of these microorganisms at this department. The results of this study suggest wide genotypic variability among the clinical VRE isolates, but also intrahospital dissemination of some of them.

The Importance of Haematological and Biochemical Findings in Patients with West Nile Virus Neuroinvasive Disease

Summary Background: West Nile virus neuroinvasive disease (WNND) occurs in less than 1% of infected people. Leukocytosis with lymphocytopenia, mild anaemia, thrombocytopenia, elevated liver and muscle enzymes and hyponatremia are occasionally present in patients with WNND. Cerebrospinal fluid (CSF) findings resemble other viral neuroinfections. The purpose of this study is to present some of the most important laboratory findings of our patients with WNND and to evaluate their correlation with fatal outcome. Methods: The study included 161 patients with WNND. Their blood and CSF samples were cytobiochemically analysed and the obtained variables were then tested for predictive significance of the disease outcome, or used for differentiation between two clinical syndromes (encephalitis vs meningitis). Results: West Nile encephalitis was present in 127 (78.9%) patients and West Nile meningitis was diagnosed in 34 (21.1%) cases. Leukocytosis was found in 45.9% patients. CRP level higher than 100 mg/L was registered only in those with encephalitis (p=0.020). CSF leukocyte count was 146±171 per microlitre, with slight lymphocytic predominance (mean 52%). Hypoglycorrhachia was registered in 9.3% of our patients with WNND. Twenty-eight (17.4%) patients died and all of them had encephalitis. Independent predictors of fatal outcome in WNND were serum CRP > 100 mg/L (p=0.011) and CSF proteins > 1 g/L (p=0.002). Conclusions: WNND usually affects older males. Prolonged neutrophilic predominance in CSF can occasionally be present, as well as hypoglycorrhachia. Patients with encephalitis, high serum CRP and high CSF protein level have a higher risk of fatal outcome.