We describe the first reported outbreak of West Nile virus (WNV) infection in humans in Serbia in August to October 2012 and examine the association of various variables with encephalitis and fatal outcome. Enzyme-linked immunosorbent assay (ELISA) was used for detection of WNV-specific IgM and IgG antibodies in sera and cerebrospinal fluid. A total of 58 patients (mean age: 61 years; standard deviation: 15) were analysed: 44 were from Belgrade and its suburbs; 52 had neuroinvasive disease, of whom 8 had meningitis, while 44 had encephalitis. Acute flaccid paralysis developed in 13 of the patients with encephalitis. Age over 60 years and immunosuppression (including diabetes) were independently associated with the development of encephalitis in a multivariate analysis: odds ratio (OR): 44.8 (95% confidence interval (CI): 4.93-408.59); p=0.001 (age over 60 years); OR: 10.76 (95% CI: 1.06-109.65); p=0.045 (immunosuppression including diabetes). Respiratory failure requiring mechanical ventilation developed in 13 patients with encephalitis. A total of 35 patients had completely recovered by the time they were discharged; nine patients died. The presence of acute flaccid paralysis, consciousness impairment, respiratory failure and immunosuppression (without diabetes) were found to be associated with death in hospital in a univariate analysis (p<0.001, p=0.007, p<0.001 and p=0.010, respectively).

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.

BackgroundTuberculous meningitis (TBM) caused by Mycobacterium tuberculosis resistant to antituberculosis drugs is an increasingly common clinical problem. This study aimed to evaluate drug resistance profiles of TBM isolates in adult patients in nine European countries involving 32 centers to provide insight into the empiric treatment of TBM.MethodsMycobacterium tuberculosis was cultured from the cerebrospinal fluid (CSF) of 142 patients and was tested for susceptibility to first-line antituberculosis drugs, streptomycin (SM), isoniazid (INH), rifampicin (RIF) and ethambutol (EMB).ResultsTwenty of 142 isolates (14.1 %) were resistant to at least one antituberculosis drug, and five (3.5 %) were resistant to at least INH and RIF, [multidrug resistant (MDR)]. The resistance rate was 12, 4.9, 4.2 and 3.5 % for INH, SM, EMB and RIF, respectively. The monoresistance rate was 6.3, 1.4 and 0.7 % for INH, SM and EMB respectively. There was no monoresistance to RIF. The mortality rate was 23.8 % in fully susceptible cases while it was 33.3 % for those exhibiting monoresistance to INH, and 40 % in cases with MDR-TBM. In compared to patients without resistance to any first-line drug, the relative risk of death for INH-monoresistance and MDR-TBM was 1.60 (95 % CI, 0.38–6.82) and 2.14 (95 % CI, 0:34–13:42), respectively.ConclusionINH-resistance and MDR rates seemed not to be worrisome in our study. However, considering their adverse effects on treatment, rapid detection of resistance to at least INH and RIF would be most beneficial for designing anti-TB therapy. Still, empiric TBM treatment should be started immediately without waiting the drug susceptibility testing.

Neurologic manifestations are prominent characteristic of West Nile virus (WNV) infection. The aim of this article was to describe neurological manifestations in patients with WNV neuroinvasive disease and their functional outcome at discharge in the first human outbreak of WNV infection in Serbia. The study enrolled patients treated in the Clinic for Infectious and Tropical Diseases, Clinical Center Serbia in Belgrade, with serological evidence of acute WNV infection who presented with meningitis, encephalitis and/or acute flaccid paralyses (AFP). Functional outcome at discharge was assessed using modified Rankin Scale (mRS) and Barthel index. Fifty-two patients were analysed. Forty-four (84.6 %) patients had encephalitis, eight (15.4 %) had meningitis, and 13 (25 %) had AFP. Among patients with AFP, 12 resembled poliomyelitis and one had clinical and electrodiagnostic findings consistent with polyradiculoneuritis. Among patients with encephalitis, 17 (32.7 %) had clinical signs of rhombencephalitis, and eight (15.4 %) presented with cerebellitis. Respiratory failure with subsequent mechanical ventilation developed in 13 patients with WNE (29.5 %). Nine (17.3 %) patients died, five (9.6 %) were functionally dependent (mRS 3-5), and 38 (73.1 %) were functionally independent at discharge (mRS 0-2). In univariate analysis, the presence of AFP, respiratory failure and consciousness impairment were found to be predictors of fatal outcome in patients with WNV neuroinvasive disease (p < 0.001, p < 0.001, p = 0.018, respectively). The outbreak of human WNV infection in Serbia caused a notable case fatality ratio, especially in patients with AFP, respiratory failure and consciousness impairment. Rhombencephalitis and cerebellitis could be underestimated presentations of WNV neuroinvasive disease.

Background Tuberculous meningitis (TBM) represents a diagnostic and management challenge to clinicians. The “Thwaites’ system” and “Lancet consensus scoring system” are utilized to differentiate TBM from bacterial meningitis but their utility in subacute and chronic meningitis where TBM is an important consideration is unknown. Methods A multicenter retrospective study of adults with subacute and chronic meningitis, defined by symptoms greater than 5 days and less than 30 days for subacute meningitis (SAM) and greater than 30 days for chronic meningitis (CM). The “Thwaites’ system” and “Lancet consensus scoring system” scores and the diagnostic accuracy by sensitivity, specificity, and area under the curve of receiver operating curve (AUC-ROC) were calculated. The “Thwaites’ system” and “Lancet consensus scoring system” suggest a high probability of TBM with scores ≤4, and with scores of ≥12, respectively. Results A total of 395 patients were identified; 313 (79.2%) had subacute and 82 (20.8%) with chronic meningitis. Patients with chronic meningitis were more likely caused by tuberculosis and had higher rates of HIV infection (P < 0.001). A total of 162 patients with TBM and 233 patients with non-TBM had unknown (140, 60.1%), fungal (41, 17.6%), viral (29, 12.4%), miscellaneous (16, 6.7%), and bacterial (7, 3.0%) etiologies. TMB patients were older and presented with lower Glasgow coma scores, lower CSF glucose and higher CSF protein (P < 0.001). Both criteria were able to distinguish TBM from bacterial meningitis; only the Lancet score was able to differentiate TBM from fungal, viral, and unknown etiologies even though significant overlap occurred between the etiologies (P < .001). Both criteria showed poor diagnostic accuracy to distinguish TBM from non-TBM etiologies (AUC-ROC was <. 5), but Lancet consensus scoring system was fair in diagnosing TBM (AUC-ROC was .738), sensitivity of 50%, and specificity of 89.3%. Conclusion Both criteria can be helpful in distinguishing TBM from bacterial meningitis, but only the Lancet consensus scoring system can help differentiate TBM from meningitis caused by fungal, viral and unknown etiologies even though significant overlap occurs and the overall diagnostic accuracy of both criteria were either poor or fair.

Summary:A retrospective study of the course and outcome of trichinellosis in a series of 50 patients hospitalized at the Institute for Infectious and Tropical Diseases in Belgrade between 2001 and 2008 was performed. Clinical diagnosis of trichinellosis was based upon the patients' clinical history, symptoms and signs, and eosinophilia. The occurrence of cases showed a strong seasonality (P < 0.0001). The incubation period ranged between one and 33 days. The mean time between onset of symptoms and admission was nine days. Family outbreaks were the most frequent. Smoked pork products were the dominant source of infection (76 %). Fever was the most frequent clinical manifestation (90 %), followed by myalgia (80 %) and periorbital edema (76 %). 43 patients were examined serologically and 72 % of them had anti-Trichinella antibodies. Eosinophilia and elevated levels of serum CK and LDH were detected in 94, 50 and 56 % of the patients, respectively. All patients responded favorably to treatment with mebendazole or albendazole, but eight developed transient complications. Trichinellosis remains a major public health issue in Serbia.

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.

Background:Trichinellosis is a zoonosis that can be prevented by veterinarian examination of meat and adequate cooking. Principal source of infection is meat of domestic or wild swine, infected with larval form of trichinella spiralis. The parasite is disseminated trough organism by blood stream,there is an inflammatory response in all tissues in which it is stuck, so any kind of complications can be expected, among them heart, brain and lung complications are tme most prominent.Methods & Materials: 53 patients were hospitalized. Illness was presented with swelling of the face, hands and feet, conjunctivitis or subconjunctival haemorrhages, with prominent muscle aches and fever. Suspicion was made on the basis of clinical findings and eosinophilia in peripheral blood count. Serology was performed as verification test. (ELISA method, Ridascreen and Novagnost).Results: Patients had 20 to 76 years (42.3 ± 14.5). Men/women ratio was 1:2,3 (p = 0,003). All were able to "blame" specific meat, to specify quantity, time and place when they eat infected meat. Time from beginning of symptoms to the suspicion was 3 to 30 days (11.09 ± 6.38). During that time they had fever, 60% had gastrointestinal symptoms, 27% eyelid swelling, 19% muscle aces. All patients (100%) had absolute eosinophilia and elevated C reactive protein (48,7 ± 31,1;norm. < 8). Lactat dechidrogenasis(LDH) was elevated in 90% of patients (682,2 ± 279,1;norm. < 400), creatin kinasis (CK) was elevated in 80% of patients (635 ± 351;norm. < 200). In two patients transitory EKG changes were seen, and another two patients had long time neurologic abnormalities. Hospitalization time was 15,6 ± 6 days. All of them were treated by albendasole or mebendasole. Highest number of cases was from January to March. Conclusion:Trichinellosis is constantly present in Belgrade aerie. It occurs relatively rarely, but we have to be aware of its presence and think of it before prominent features appear, in order to perform adequate early therapy, any delay in diagnosis could lead to worst illness. The most reliably tool is eosinophilia, supported by relevant epidemiologic data. Convalescent period during which muscle aches are prominent can last for years, what is especially important in sportsmen.