A patient with respiratory toxigenic diphtheria in Greece after more than 30 years.

The introduction of treatment and systematic vaccination has significantly reduced diphtheria mortality; however, toxigenic strains continue to circulate worldwide. The emergence of an indigenous diphtheria case with fatal outcome in Greece, after 30 years, raised challenges for laboratory confirmation, clinical and public health management. Toxigenic Corynebacterium diphtheriae was isolated from an incompletely vaccinated 8-year-old boy with underlying conditions. The child passed away due to respiratory distress syndrome, before the administration of diphtheria antitoxin (DAT). All close contacts in family, school and hospital settings were investigated. Pharyngeal swabs were obtained to determine asymptomatic carriage. Chemoprophylaxis was given for 7 days to all close contacts and a booster dose to those incompletely vaccinated. Testing revealed a classmate, belonging to a subpopulation group (Roma), and incompletely vaccinated, as an asymptomatic carrier with an indistinguishable toxigenic strain (same novel multilocus sequence type, designated ST698). This case highlights the role of asymptomatic carriage, as the entry of toxigenic strains into susceptible populations can put individuals and their environment at risk. Maintenance of high-level epidemiological and microbiological surveillance, implementation of systematic vaccination in children and adults with primary and booster doses, availability of a DAT stockpile, and allowing timely administration are the cornerstone to prevent similar incidents in the future.

A case of imported Middle East Respiratory Syndrome coronavirus infection and public health response, Greece, April 2014.

On 18 April 2014, a case of Middle East Respiratory Syndrome coronavirus (MERS-CoV) infection was laboratory confirmed in Athens, Greece in a patient returning from Jeddah, Saudi Arabia. Main symptoms upon initial presentation were protracted fever and diarrhoea, during hospitalisation he developed bilateral pneumonia and his condition worsened. During 14 days prior to onset of illness, he had extensive contact with the healthcare environment in Jeddah. Contact tracing revealed 73 contacts, no secondary cases had occurred by 22 April.

Effect of hepatitis C virus on immunological and virological responses in HIV-infected patients initiating highly active antiretroviral therapy: a meta-analysis.

Co-infection of human immunodeficiency virus (HIV) with hepatitis C virus (HCV) is rather common. In the era of highly active antiretroviral therapy (HAART), viral hepatitis could result in adverse outcomes in HIV+ patients. The current meta-analysis aims to evaluate the impact of HCV on immunological and virological responses after HAART initiation in HIV/HCV co-infected individuals by synthesizing the existing scientific evidence. A comprehensive search of electronic databases was performed. Eligible studies were analysed using univariate and multivariate meta-analytic methods. Totally, 21 studies involving 22533 individuals were eligible. The estimated summary difference in CD4 cell counts increase between HIV and HIV/HCV co-infected subjects after 3-12 months on HAART was 34.86 cells/mm(3) [95% confidence interval (CI): 16.82-52.89]. The difference was more prominent in patients with baseline CD4 counts below 350 cells/mm(3) (38.97, 95% CI: 20.00-57.93) and attenuated 2 years later (13.43, 95% CI: 0.83-26.04). The analysis of ratio measures yielded similar findings. The virological control remained unaffected by the presence of HCV (adjusted Hazard Ratio for co-infected patients vs those with HIV alone: 0.99, 95% CI: 0.91-1.07). The bivariate meta-analytic method confirmed the results of the univariate approaches. This meta-analysis supports the adverse effect of HCV on immune recovery of HIV+ patients initiating HAART, especially of those with initially impaired immunologic status. Although this effect diminishes over time, early administration of HAART in the setting of co-infection seems to be justified.

Risk factors for sporadic Campylobacter jejuni infections in children in a Greek region.

A case-control study was conducted in the urban area of Attica, Greece to investigate risk factors for sporadic Campylobacter jejuni infections in children aged <15 years. Over a 2-year period, 205 cases and 205 controls, matched by age group (<1, 1-4, 5-9, 10-14 years) and gender, were selected from the registries of the paediatric hospitals of this area. In conditional multivariate logistic regression analysis, ethnicity [odds ratio (OR) 5·06, 95% confidence interval (CI) 2·49-10·28], consumption of chicken the week prior to disease onset (OR 1·97, 95% CI 1·10-3·55) and playing in the garden (OR 1·83, 95% CI 1·05-3·19) were independently associated with disease occurrence; consumption of raw vegetables was a 'protective' factor (OR 0·48, 95% CI 0·27-0·85).

Heart transplantation in a low-organ-donation environment: a single center experience.

OBJECTIVE: Heart transplantation is the "gold standard" for treating patients in end-stage heart failure who satisfy strict selection criteria. However, infrequent transplant performance, eg, less than nine per year, may be associated with suboptimal results. METHODS: We reviewed our 13-year clinical experience (1996-2008) with 73 orthotopic heart transplants performed under strict selection criteria and followed closely thereafter at the only accredited center in Greece, a country with an annual rate of only seven donors per million population. RESULTS: Low perioperative (5.47%) and long-term (7.5%) mortality rates were responsible for a 94% survival rate in the first year, 92% at five years, and 70% at ten years-similar to those reported worldwide-along with excellent functional recovery. CONCLUSION: Strict recipient and donor selection criteria, combined with a rigorous multidisciplinary follow-up, yield excellent results despite the existing shortage of available grafts.

Predictive value of complete and partial early virological response on sustained virological response rates of genotype-4 chronic hepatitis C patients treated with PEG-interferon plus ribavirin.

OBJECTIVES: To investigate early viral kinetics, sustained virological response (SVR) rates and their predictors, in treatment-naïve, genotype-4-infected, chronic hepatitis C (CHC) patients treated with PEG-IFNalpha2b plus ribavirin. PATIENTS AND METHODS: In total, 58 patients were retrospectively analyzed. Early virological response (EVR) was defined as undetectable HCV-RNA (<50 IU/ml) at week 12 (complete, cEVR) or at least a 2 log decrease in HCV-RNA levels (partial, pEVR). RESULTS: Thirty-one patients exhibited SVR (53.4%), 17 (29.3%) were non-responders and 10 (17.2%) relapsed. Thirty-seven patients (63.8%) exhibited EVR. The positive predictive values of EVR, cEVR and pEVR for the SVR achievement were 83.87, 54.83, and 29.03%, whereas their negative predictive values were 59.25, 77.77, and 81.48%, respectively. Both cEVR (OR 0.040, p = 0.042) and EVR (OR 0.016, p = 0.006) independently predicted SVR. Baseline viral load (p < 0.001), age (p = 0.035) and stage of liver disease (p = 0.04) were significantly related to the EVR achievement, whereas only baseline viral load (p = 0.003) and ethnicity (p = 0.025) predicted cEVR. CONCLUSIONS: Partial or complete EVR represent independent predictors of SVR in genotype-4-infected CHC patients, regardless of their baseline parameters. The absence of pEVR, rather than the absence of cEVR, should be used as an early indication for discontinuation of treatment in these patients.

KPC-2-producing Klebsiella pneumoniae infections in Greek hospitals are mainly due to a hyperepidemic clone.

To verify the presence of Klebsiella pneumoniae carbapenemase-producing (KPC-producing) Klebsiella pneumoniae in Greece, we asked 40 Greek hospitals participating in the Greek System for the Surveillance of Antimicrobial Resistance (GSSAR) to apply a combination of the modified Hodge test plus EDTA synergy test on all K. pneumoniae clinical isolates obtained from February 2008 which displayed reduced susceptibility to carbapenems (MIC of imipenem > or = 1 mg/L). The presence of the blaKPC gene was confirmed by PCR and sequencing. This procedure revealed the presence of KPC-2 in isolates from 173 patients in 18 hospitals during a period of 11 months. Of these, 166 isolates belonged to a single pulsotype a fact consistent with possible epidemic spread, whereas the remaining seven isolates were further classified into four different pulsotypes. BlaKPC-2 gene was found to be transferable by conjugation in the four pulsotypes other than the prevailing one. The emergence of a new carbapenemase gene in Greece, where high resistance rates to carbapenems in K. pneumoniae due to the spread of the VIM type metalloenzyme have been observed, emphasises the urgent need for the implementation of public health measures in the field of infection control and antibiotic consumption. It also underlines the need to supplement surveillance systems based on susceptibility data with the surveillance of resistance mechanisms.

Clinical significance of hepatitis B surface antigen in cord blood of hepatitis B e-antigen-negative chronic hepatitis B virus-infected mothers.

Vertical transmission of hepatitis B virus (HBV) infection during the perinatal period is the major cause of HBV transmission. The aim of our study was to evaluate the serological and virological profiles of HBV infection in cord blood samples obtained from HBeAg-negative chronic HBV-infected women, at delivery, and to investigate their relationship with the clinical outcome (possible transmission of HBV) in neonates receiving the currently approved passive-active immunoprophylaxis schedule. Sixteen women (32%) exhibited HBsAg positivity in the cord blood but HBV-DNA has not been detected in any of the 50 cord blood samples evaluated. We conclude that HBsAg can be transferred through the placental barrier, as with other proteins, in about one third of HBeAg-negative chronic HBV-infected pregnant women, irrespective of the maternal viral load, the mode of delivery or the placenta HBV pathology. The clinical impact of this phenomenon on the intrauterine-transplacental or perinatal transmission of HBV infection and/or passive-active immunoprophylaxis failure does not seem to be important.

Differential viral kinetics in treated genotype 4 chronic hepatitis C patients according to ethnicity.

Data concerning the efficacy of PEG-IFN alpha 2a plus ribavirin treatment in treatment-naive, genotype 4-infected chronic hepatitis C (CHC) patients from Europe are limited. Hence the aim of this study was to investigate the viral kinetics as well as the sustained virological response (SVR) rates and their predictors, in these patients. One hundred and twenty-three patients were retrospectively analysed. Early (EVR) and late virological response (LVR) was confirmed by undetectable (<50 IU/mL) serum HCV-RNA at week 12 and week 24 of treatment, respectively. SVR was confirmed by undetectable serum HCV-RNA at the end of treatment as well as 6 months later. Overall, 43.5% of patients exhibited SVR, 42.6% were nonresponders and 13.9% were relapsers. EVR was observed in 40.74% and LVR in 59.25% of them. The positive predictive values of EVR and LVR were 72.97% and 86.27% whereas their negative predictive values were 64.29% and 92.85%, respectively. EVR independently predicted SVR in Caucasian patients (P < 0.001) but not in Egyptian patients (P = 0.613), in whom the only independent predictor of SVR was the absence of cirrhosis (P = 0.004). LVR seems to be a better predictor of SVR than EVR in the vast majority of genotype 4-infected CHC patients, irrespective of ethnicity and all the other baseline parameters.

Surveillance for hepatitis B virus infection in pregnant women in Greece shows high rates of chronic infection among immigrants and low vaccination-induced protection rates: preliminary results of a single center study.

Epidemiological data on the prevalence of serological markers of hepatitis B virus (HBV) infection in pregnant women in Greece are limited. We evaluated the prevalence of HBV serological markers in a multinational population of pregnant women in Athens, Greece. The overall prevalence of hepatitis B surface antigen (HbsAg) was 4.1% with the highest rates among Albanian immigrants (12%). Relatively low vaccination-induced protection rates (32.5%) were observed, a finding suggesting that surveillance and immunisation programmes targeted at pregnant women are necessary.

Prospective monitoring of BK virus replication in renal transplant recipients.

BACKGROUND: BK virus-associated nephropathy (BKVAN) can be diagnosed only with renal graft biopsy. Definitive diagnosis of BKVAN requires demonstration of BK virus (BKV) replication in renal allograft tissues. Non-invasive analysis of urine and blood is considered essential in screening renal transplant recipients. PATIENTS AND METHODS: This study evaluated prospectively the replication of BKV in plasma and urine with qualitative and quantitative real-time polymerase chain reaction in 32 de novo (group A) and 34 chronic (group B) renal transplant recipients and the long-term impact on graft function. RESULTS: In group A, 456 samples (228 plasma, 228 urine) were examined and BKV was detected in 31 (31/228, 14%) samples of plasma and 57 (57/228, 25%) samples of urine in 20 (20/32, 62.5%) and 23 (23/32, 72%) recipients, respectively. Incidence of viremia and viruria increased during the first 6 months presenting a peak the third postoperative month (viremia: 28% and viruria: 31%). Immune suppressive treatment with tacrolimus showed significant relation with viremia. Renal graft function in de novo renal transplant recipients remained stable throughout the follow-up period without influence of BKV replication. In group B, incidence of viremia and viruria were 3% (1/34) and 9% (3/34) correspondingly, indicating that after the first post-transplant year the risk of BKV re-activation is diminished. CONCLUSION: The highest incidence of BK viremia and viruria is observed the third post-transplantation month, confirming previously published studies in Europe and the United States, and long-term follow up shows that BKV replication decreases significantly after the third post-transplant month and even transient viremia or viruria does not have an impact on renal function.

Coxsackievirus B3 sequences in the myocardium of fatal cases in a cluster of acute myocarditis in Greece.

AIM: The investigation of three fatal cases during a nationwide cluster of cases of an upper respiratory tract infection (URTI) associated with myocarditis and/or pericarditis in Greece in 2002. METHODS: In the three women who died, necropsies were performed and tissue sections were taken for histological examination, antigen detection by immunohistochemistry and indirect immunofluorescence assay (IFA), amplification of viral genomes by nested reverse transcription polymerase chain reaction (RT-PCR), and sequence analysis. RESULTS: All samples showed histological signs of active myocarditis. Immunohistochemistry revealed the presence of the enterovirus VP1 family of proteins and IFA revealed the presence of coxsackievirus B3 antigen. Nested RT-PCR amplified enteroviral alleles of the 5'-untranslated region which were identical to each other and to the coxsackievirus B3 sequences. CONCLUSIONS: This study provides pathological evidence of enteroviral infection among fatal myocarditis cases in a nationwide URTI cluster of cases associated with myocarditis and/or pericarditis.

Infective endocarditis in Greece: a changing profile. Epidemiological, microbiological and therapeutic data.

The epidemiology, and clinical and microbiological spectrum, of infective endocarditis (IE) in Greece was analysed in a prospective 4-year study in a tertiary hospital and a heart surgery centre in Athens. In total, 101 cases of IE (71 men, 30 women, aged 54.4 +/- 17.1 years) were studied, with a follow-up period of 3 months. Seventy-seven cases were definite and 24 possible; 59 involved native valves (native valve endocarditis; NVE), 31 prosthetic valves (prosthetic valve endocarditis; PVE), of which nine were early and 22 late, and 11 permanent pacemakers (pacemaker endocarditis; PME). There was a predominant involvement of aortic (48/101) and mitral (40/101) valves. Seven patients had rheumatic valvular disease, two had mitral valve prolapse, and eight had a previous history of IE. Thirteen and six patients had undergone dental and endoscopic procedures, respectively. In 13 patients, intravenous catheters were used within the 3 months before diagnosis of IE. There were three intravenous drug users among the patients. Staphylococcus aureus was the most important pathogen, isolated in 22% of cases, followed by viridans streptococci (19%) and coagulase-negative staphylococci (16%). Enterococcus spp. were responsible for 3%, HACEK group for 2%, and fungi for 6% of cases. Viridans streptococci were the leading cause of NVE (29%), Staphylococcus epidermidis of PVE (16%), and S. aureus of PME (54.5%). Six of 22 S. aureus and ten of 16 S. epidermidis isolates were methicillin-resistant. Surgical intervention, including total pacemaker removal, was performed in 51.5% of patients. Overall mortality was 16%, but was 29% with PVE, and was significantly higher with medical than with combined surgical and medical therapy (24.5% vs. 8%). Compared with previous studies, there were changing trends in the epidemiology, microbiology, treatment and prognosis of IE in Greece.

Algorithm for statistical detection of peaks--syndromic surveillance system for the Athens 2004 Olympic Games.

INTRODUCTION: No generally accepted procedure exists for detecting outbreaks in syndromic time series used in the surveillance of natural epidemics or biologic attacks. OBJECTIVES: This report evaluates the usefulness for syndromic surveillance of the Pulsar approach, which is based on removing long-term trends from an observed series and identifying peaks in the residual series of surveillance data with cutoffs determined by using a combination of peak height and width. METHODS: Simulations were performed to evaluate the Pulsar method and compare it with other approaches. The daily syndromic counts in emergency departments of four major hospitals in the Athens area during August 2002-August 2003 were analyzed for two common syndromes. A standardized residual series was generated by omitting trends and noise in the original data series; this series was examined for the presence of peaks (i.e., points having magnitude higher than at least one of three probabilistically determined cutoffs). The whole process was iterated, and the baseline was recalculated by assigning reduced weight to the identified peaks. RESULTS: For the specific simulation schema used, the Pulsar method fared well when compared with other approaches in meeting the performance criteria of sensitivity, specificity, and timeliness. CONCLUSIONS: Although the suggested algorithm needs further validation regarding the correspondence between detected peaks and true biologic alerts, the Pulsar technique appears effective for observing peaks in time series of syndromic events. The simplicity of the algorithm, its ability to detect peaks based not only on height but also on width, and its performance in the simulated data sets make it a promising candidate for further use in syndromic surveillance.

Detection of enterococcal surface protein gene (esp) and amplified fragment length polymorphism typing of glycopeptide-resistant Enterococcus faecium during its emergence in a Greek intensive care unit.

The emergence of glycopeptide-resistant Enterococcus faecium (GREF) in a Greek intensive care unit was studied by amplified fragment length polymorphism analysis and esp gene detection. Three GREF clones harboring the esp gene were recovered from 17 out of 21 patients, indicating the dissemination of genetically homogenous and virulent strains of GREF.

Mutations associated with genotypic resistance to antiretroviral therapy in treatment naïve HIV-1 infected patients in Greece.

The widespread use of antiviral drugs against HIV has increased the prevalence of HIV-1 resistant strains among naïve individuals due to transmission of resistant strains. The purpose of this study was to investigate the presence of HIV-1 strains harboring resistance mutations in naïve patients in Greece. Blood samples were collected from 25 individuals. The DNA sequence of protease and partial reverse transcriptase regions (codons 41-223) were obtained by direct sequencing. Our results showed the absence of any primary resistance mutations in the study population. However, we were able to identify high prevalence of sequence polymorphisms at positions in reverse transcriptase region associated mainly with resistance to NNRTIs. Moreover, in protease region several secondary mutations were detected, suggesting the higher genetic variability of this region. The clinical significance of the polymorphisms associated with reduced susceptibility to NNRTIs remains to be clarified.

Enterococcal infections in a Greek intensive care unit: a 5-y study.

In this study we determined the incidence, resistance pattern, and mortality rate associated with infection caused by Enterococcus faecalis and Enterococcus faecium among patients in a multidisciplinary intensive care unit (ICU). A total of 111 patients with E. faecalis and 60 with E. faecium infections were identified during a 5-y period (1992-96). We observed an increase in the incidence of enterococcal infections (from 5.46 to 8.46 per 1000 patients-days, p = 0.0112), due mainly to the increased incidence of E. faecium (from 0.45 to 4.06 per 1000 patients-days, p = 0.002). Blood was the most common site of enterococcus isolation. E. faecium was more resistant to antibiotics than E. faecalis, but no vancomycin resistant enterococcus was isolated. Patients with E. faecium infection had a significantly higher mortality than patients with E. faecalis infection (66% vs. 41.5%, p = 0.0035 for infection from any site and 85.7 vs. 47.7%, p = 0.012 for bacteremic patients). r 4n- D I .- .- - .. . .