An outbreak of haemorrhagic fever with renal syndrome linked with mountain recreational activities in Zagreb, Croatia, 2017.

In 2017 Zagreb faced the largest outbreak of haemorrhagic fever with renal syndrome (HFRS) to date. We investigated to describe the extent of the outbreak and identify risk factors for infection. We compared laboratory-confirmed cases of Hantavirus infection in Zagreb residents with the onset of illness after 1 January 2017, with individually matched controls from the same household or neighbourhood. We calculated adjusted matched odds ratios (amOR) using conditional logistic regression. During 2017, 104 cases were reported: 11-81 years old (median 37) and 71% (73) male. Compared with 104 controls, cases were more likely to report visiting Mount Medvednica (amOR 60, 95% CI 6-597), visiting a forest (amOR 46, 95% CI 4.7-450) and observing rodents (amOR 20, 95% CI 2.6-159). Seventy per cent of cases (73/104) had visited Mount Medvednica prior to infection. Among participants who had visited Mount Medvednica, cases were more likely to have drunk water from a spring (amOR 22, 95% CI 1.9-265), observed rodents (amOR 17, 95% CI 2-144), picked flowers (amOR 15, 95% CI 1.2-182) or cycled (amOR 14, 95% CI 1.6-135). Our study indicated that recreational activity around Mount Medvednica was associated with HFRS. We recommend enhanced surveillance of the recreational areas during an outbreak.

Hepatitis E in patients with hepatic disorders and HIV-infected patients in Croatia: is one diagnostic method enough for hepatitis E diagnosis?

We assessed hepatitis E virus (HEV) seroprevalence in patients with hepatic disorders as well as in human immunodeficiency virus (HIV)-infected patients and emphasised the issue of possible non-specific anti-HEV seroresponse and need for combining diagnostic methods for hepatitis E diagnosis. Over a two-year period, from March 2011 to February 2013, we determined anti-HEV immunoglobulin M (IgM) and IgG by enzyme immunoassays (EIA; Mikrogen, Germany) in 504 hepatitis patients negative for acute viral hepatitis A-C. Furthermore, 88 samples from randomly selected consecutive HIV-infected patients were also analysed. All EIA reactive samples were additionally tested by line immunoblot assays (LIA; Mikrogen, Germany). HEV nested reverse transcription polymerase chain reaction (RT-PCR) was carried out in 14 anti-HEV IgM LIA-positive patients. Anti-HEV IgM or IgG were detected in 16.9 % of patients by EIA and confirmed by LIA in 10.7 % [95 % confidence interval (CI) 8.3-13.7 %] of hepatitis patients. HEV RNA was detected in five patients. The agreement between EIA and LIA assessed by Cohen's kappa was 0.47 (95 % CI 0.55-0.75) for IgM and 0.83 (95 % CI 0.78-0.93) for IgG. Anti-HEV IgM and IgG seroprevalence in HIV-infected patients was 1.1 %, respectively. Our findings show a rather high HEV seroprevalence in patients with elevated liver enzymes in comparison to HIV-infected patients. Discordant findings by different methods stress the need to combine complementary methods and use a two-tier approach with prudent interpretation of reactive serological results for hepatitis E diagnosis.

Molecular characterization of dengue virus 1 from autochthonous dengue fever cases in Croatia.

In the summer of 2010, two autochthonous dengue fever cases were detected in Croatia. Here we report the retrospective detection of an additional case of dengue fever, representing the first sustained autochthonous transmission in Europe since 1928. In addition, we present the phylogenetic analyses based on two sequences from the Peljesac peninsula, southern Croatia. The sequences were identified as dengue virus genotype 1 and recovered from two out of the three Peljesac patients in whom infection occurred.

Serum apoptosis markers in HIV-infected patients with human herpesvirus type 8 and herpes simplex virus type 2 co-infection.

This study aimed to examine the influence of human herpesvirus type 8 (HHV-8) and herpes simplex virus type 2 (HSV-2) co-infections on apoptosis serum markers in human immunodeficiency virus (HIV)-infected patients. Sera from 110 HIV-infected and 59 HIV-uninfected individuals were analyzed for soluble Fas (sFas), sFas ligand (sFasL), caspase-8, and Bcl-2. The findings of HIV-infected patients with no co-infection (n = 37), HIV-infected patients with HHV-8 co-infection (n = 22), HIV-infected patients with HSV-2 co-infection (n = 51), and patients with HSV-2 co-infection and no HIV infection (n = 20) were compared to controls (reference group) with no HIV, HSV-2, and HHV-8 co-infections (n = 39). Soluble Fas and sFasL concentrations were the highest in HIV and HHV-8 co-infected patients (medians, 912.7 pg/ml and 74.3 pg/mL, respectively). No difference in caspase-8 concentrations was found, whereas Bcl-2 concentrations were the highest in HIV and HHV-8 co-infected individuals. Older age was associated with higher sFas (p < 0.001) and lower sFasL (p = 0.04) concentrations. In a robust regression model adjusted for age, the log-transformed sFas concentrations were significantly lower in HIV-infected patients with no co-infections (ß = -0.244; p < 0.001) and higher in HIV and HHV-8 co-infected patients (ß = 0.216; p = 0.012) compared to the reference group. Soluble FasL was significantly lower in HIV-infected patients with no co-infections (ß = -0.284; p = 0.005) and in HIV-infected patients with HSV-2 co-infection (ß = -0.381; p < 0.001) compared to the reference group. Soluble FasL was also higher in HIV and HHV-8 co-infected patients compared to controls (ß = 0.248; p = 0.036). Our results suggest that HHV-8 and HSV-2 may have a significant effect on Fas-FasL-mediated apoptosis in HIV-1 patients. HHV-8 upregulates while HSV-2 downregulates sFas and sFasL.

Chlamydia pneumoniae and Mycoplasma pneumoniae pneumonia: comparison of clinical, epidemiological characteristics and laboratory profiles.

The purpose of our retrospective 3-year study was to analyse and compare clinical and epidemiological characteristics in hospitalized patients older than 6 years with community-acquired pneumonia (CAP) caused by Chlamydia pneumoniae (87 patients) and Mycoplasma pneumoniae (147 patients). C. pneumoniae and M. pneumoniae infection was confirmed by serology. C. pneumoniae patients were older (42.12 vs. 24.64 years), and were less likely to have a cough, rhinitis, and hoarseness (P<0.001). C. pneumoniae patients had higher levels of C-reactive protein (CRP), and aspartate aminotransferase (AST) than M. pneumoniae patients (P<0.001). Pleural effusion was recorded more frequently in patients with M. pneumoniae (8.84 vs. 3.37%). There were no characteristic epidemiological and clinical findings that would distinguish CAP caused by M. pneumoniae from C. pneumoniae. However, some factors are indicative for C. pneumoniae such as older age, lack of cough, rhinitis, hoarseness, and higher value of CRP, and AST.

Clinical efficacy and safety of a short regimen of azithromycin sequential therapy vs standard cefuroxime sequential therapy in the treatment of community-acquired pneumonia: an international, randomized, open-label study.

An international, randomized, open-label, comparative study was undertaken in order to assess the efficacy and safety of azithromycin and cefuroxime, short sequential vs standard sequential therapy, respectively, in the treatment of patients with community-acquired pneumonia (CAP). 180 adult patients were included in the study. 89 patients received azithromycin 500 mg intravenously (i.v.) once daily for 1-4 days followed by azithromycin 500 mg orally once daily for 3 days. 91 patients received cefuroxime 1.5 g i.v. three times daily for 1-4 days followed by cefuroxime axetil 500 mg orally twice daily for 7 days. Clinical efficacy was achieved in 67/82 (81.7%) patients treated with azithromycin, and in 73/89 (82.0%) patients treated with cefuroxime. The mean duration of total (i.v. and oral) therapy was significantly shorter for the azithromycin group than for the cefuroxime group (6.2 days vs 10.1 days). Adverse events were recorded in 38.2% of patients treated with azithromycin, and in 29.7% of patients treated with cefuroxime (p = 0.20). Shorter sequential i.v.-to-oral azithromycin therapy of patients with CAP was as effective as standard sequential i.v.-to-oral cefuroxime therapy.

Increased numbers of CD38 molecules on bright CD8+ T lymphocytes in infectious mononucleosis caused by Epstein-Barr virus infection.

The aim of this study was to quantify the expression of CD38 on CD8+ T lymphocytes of patients with infectious mononucleosis (IM) caused by Epstein-Barr virus (EBV) and cytomegalovirus (CMV). CD38 quantification technique chosen for this study was based on the enumeration of CD38 antibody binding sites in comparison to the quantification standards rather than determining relative fluorescence, which is difficult to standardize. The study enrolled 19 patients with typical clinical and laboratory parameters compatible with EBV-induced IM as well as 10 patients with atypical clinical presentation of this disease. Furthermore, CD38 expression was analysed in a group of 13 patients with IM caused by CMV infection. CD38 quantification was performed within 6 days of the presentation of symptoms. All three groups of IM patients showed a statistically significant increase in the number of anti-CD38 antibody binding sites (which correspond to the number of CD38 molecules) on bright CD8+ T lymphocytes compared to healthy controls. The numbers of CD38 molecules expressed on CD8+ T lymphocytes did not differ significantly between IM patients with typical and atypical clinical presentation of the disease. Patients with CMV-induced IM had significantly lower numbers of CD38 molecules expressed on CD8+ T lymphocytes. Therefore, we conclude that CD38 quantification could be helpful in differential diagnostics of IM cases with atypical clinical presentation.

-Immunization of hospital personnel at the Sestre Milosrdnice Hospital against viral hepatitis B. / Zastita djelatnika klinicke bolnice "Sestre milosrdnice" od infekcije virusom hepatitisa B.

The results of vaccination against hepatitis B among health-care workers in "Sestre Milosrdnice" University Hospital are presented. Out of 1884 health-care workers 920 (48.8%) were tested for serum HbsAg, as well as anti-HBs and anti-HBc antibodies. There were 111 (12.1%) persons with one or more positive HBV markers. Seven of them (0.8%) were HBV (HbsA-positive) carriers, and 104 (11.3%) had positive anti-HBc and/or anti-HBs. A significant difference of frequency of positive HBV markers between women and men was not found using the chi 2 test for statistical analysis. The vaccination was started in 583 (72.1%) out of 809 examinees with negative HBV markers, out of which 339 (41.9%) received complete three doses and 244 (30.2%) only one or two doses of vaccine. Even 226 (27.9%) persons susceptible to HBV infection refused the vaccination, and other 244 (30.2%) examinees did not receive the complete vaccination course. Therefore, the pre-testing showed that in 12.1% of examinees there was no need for vaccination, which means the saving of 333 bottles of vaccine. Totally 470 health-care workers out of 809 liable to HBV infection were not protected by this action, in full 58.1%! Out of 1884 health-care workers in "Sestre Milosrdnice" University Hospital even 964 (51.2%) refused the testing.