Invasive meningococcal disease epidemiology and vaccination strategies in four Southern European countries: a review of the available data.

INTRODUCTION: Invasive meningococcal disease (IMD) is a major health concern which can be prevented through vaccination. Conjugate vaccines against serogroups A, C, W, and Y and two protein-based vaccines against serogroup B are currently available in the European Union. AREAS COVERED: We present epidemiologic data for Italy, Portugal, Greece, and Spain using publicly available reports from national reference laboratories and national or regional immunization programs (1999-2019), aiming to confirm risk groups, and describe time trends in overall incidence and serogroup distribution, as well as impact of immunization. Analysis of circulating MenB isolates in terms of the surface factor H binding protein (fHbp) using PubMLST is discussed as fHbp represents an important MenB vaccine antigen. Predictions of potential reactivity of the two available MenB vaccines (MenB-fHbp and 4CMenB) with circulating MenB isolates are also provided as assessed using the recently developed MenDeVAR tool. EXPERT OPINION: Understanding dynamics of IMD and continued genomic surveillance are essential for evaluating vaccine effectiveness, but also prompting proactive immunization programs to prevent future outbreaks. Importantly, the successful design of further effective meningococcal vaccines to fight IMD relies on considering the unpredictable epidemiology of the disease and combining lessons learnt from capsule polysaccharide vaccines and protein-based vaccines.

Quality of Life Outcomes in Frontal Sinus Surgery.

INTRODUCTION: Although significant experience has been gained in the technical nuances of endoscopic sinus surgery procedures, the patient-reported outcomes of frontal endoscopic sinus surgery procedures are still poorly understood. In this study we used the validated patient outcome measure Sino Nasal Outcome Test-22 (SNOT-22) to assess the preoperative and postoperative quality of life in patients undergoing extended endoscopic frontal sinus surgery (Draf type 2 and Draf type 3 procedures). METHODS: Out of a total of 680 patients undergoing endoscopic sinus and skull base surgery and 186 patients undergoing frontal sinus surgery, 99 chronic rhinosinusitis patients with (CRSwNP) or without (CRSnNP) nasal polyps undergoing Draf 2 or Draf 3 were assessed. RESULTS: The mean preoperative SNOT-22 was 45.6 points for patients undergoing Draf 2 and 59 for patients undergoing Draf 3, while the mean radiological Lund-Mackay Score was 14.3 and 14.5, respectively. Mean SNOT 22 improvement was 22.9 points for Draf 2 and 37 points for Draf 3 respectively and remained significant in all time intervals, including at 4 years after surgery. With the exception of loss of smell/taste, all symptoms improved by a far bigger extent in Draf 3 group, despite the considerably worse starting point. Effect size (Cohen / Standard Deviations) of Draf 3 was greatest in the following symptoms: "being frustrated/restless/irritable" (1.63), "nasal blockage" (1.43), "reduced concentration" (1.35), "fatigue" (1.29) "runny nose" (1.26) and "need to blow nose" (1.17). Frontal sinus (neo) ostium was patent (fully or partly) at last follow up in 98% of Draf 2 patients and in 88% of patients following Draf 3. Patients with non-patent frontal (neo-) ostium however had a mean postoperative SNOT 22 score of 43 compared to 20 of those with patent frontal sinus (neo-) ostium, although the difference was not statistically significant. CONCLUSION: Patients undergoing Draf 3 have a greater burden of disease, including both nasal and emotional/general symptoms compared to Draf 2 patients; surgery results in improvement in both groups, although Draf 3 patients have the greatest benefit, especially in emotional / general symptons. In this way both groups achieve similar postoperative quality of life, despite the different starting points.

Comparison Between Carbapenems and ß-Lactam/ß-Lactamase Inhibitors in the Treatment for Bloodstream Infections Caused by Extended-Spectrum ß-Lactamase-Producing Enterobacteriaceae: A Systematic Review and Meta-Analysis.

BACKGROUND: Carbapenems are widely used for the management of bloodstream infections (BSIs) caused by extended-spectrum ß-lactamase-producing Enterobacteriaceae (ESBL-PE). However, the wide use of carbapenems has been associated with carbapenem-resistant Enterobacteriaceae development. METHODS: We searched the PubMed and Scopus databases (last search date was on June 1, 2016) looking for studies that reported mortality in adult patients with ESBL-PE BSIs that were treated with carbapenems or ß-lactam/ß-lactamase inhibitors (BL/BLIs). RESULTS: Fourteen studies reported mortality data in adult patients with ESBL-PE BSI that were treated with carbapenems or BL/BLIs. Among them, 13 studies reported extractable data on empiric therapy, with no statistically significant difference in mortality of patients with ESBL-PE BSI that were treated empirically with carbapenems (22.1%; 121 of 547), compared with those that received empiric BL/BLIs (20.5%; 109 of 531; relative risk [RR], 1.05; 95% confidence interval [CI], 0.83-1.37; I2 = 20.7%; P = .241). In addition, 7 studies reported data on definitive therapy. In total, 767 patients (79.3%) received carbapenems and 199 patients (20.6%) received BL/BLIs as definitive therapy, and there was again no statistically significant difference (RR, 0.62; 95% CI, 0.25-1.52; I2 = 84.6%; P < .001). Regarding specific pathogens, the use of empiric BL/BLIs in patients with BSI due to ESBL-Escherichia coli was not associated with a statistically significant difference in mortality (RR, 1.014; 95% CI, 0.491-2.095; I2 = 62.5%; P = .046), compared with the use of empiric carbapenems. CONCLUSIONS: These data do not support the wide use of carbapenems as empiric therapy, and BL/BLIs might be effective agents for initial/empiric therapy for patients with BSI caused by likely ESBL-PE, and especially ESBL-E coli.

Vancomycin-resistant enterococci colonisation, risk factors and risk for infection among hospitalised paediatric patients: a systematic review and meta-analysis.

The objective of this study was to estimate the rate and significance of colonisation with vancomycin-resistant enterococci (VRE) among hospitalised children. The PubMed and EMBASE databases were systematically searched (last accessed on 29 May 2016) to identify studies evaluating VRE colonisation of the gastrointestinal tract of hospitalised children in non-outbreak periods. Of 945 non-duplicate citations, 19 studies enrolling 20 234 children were included. The overall and paediatric intensive care unit (PICU) rate of VRE colonisation were both 5% [95% confidence interval (CI) 3-8% overall and 95% CI 2-9% in the PICU] but was 23% in haematology/oncology units (95% CI 18-29%). Studies that were exclusively performed in haematology/oncology units reported significantly higher rates compared with all other studies in the univariate and multivariate analyses (P = 0.001). Previous vancomycin [risk ratio (RR) = 4.34, 95% CI 2.77-6.82] or ceftazidime (RR = 4.15, 95% CI 2.69-6.40) use was a risk factor for VRE colonisation. Importantly, VRE colonisation increased the risk of subsequent VRE infection (RR = 8.75, 95% CI 3.19-23.97). In conclusion, a high rate of VRE colonisation was found among hospitalised children in institutions that performed targeted screening. Importantly, colonised children were almost 9 times more likely to develop subsequent VRE infection. Judicious use of specific antibiotics along with intensification of infection control measures should be considered in high-prevalence institutions. Also, the high incidence of VRE colonisation among children with haematological/oncological diseases identifies a high-risk population.

Factors Associated with HIV Testing and HIV Treatment Adherence: A Systematic Review.

BACKGROUND: The impact of the global economic crisis on HIV-related access and care remains unclear. The objective of this systematic review of the literature was to evaluate the association between socioeconomic factors and HIV diagnosis, and adherence to treatment, following the 2008 global economic crisis. METHOD: A systematic search of PubMed and Scopus for studies published between January 2008 and October 2016 was conducted. Studies providing data on social, demographic, economic and cultural barriers associated with HIV diagnosis and treatment were included. RESULTS: Of 33 studies included, 22 evaluated HIV testing and 11 evaluated treatment adherence. Medical history of a sexually transmitted disease, knowledge of HIV-related risks, and age, were significantly associated with HIV testing in most of the included studies. Absence of social support, and alcohol or substance use, were the most common factors associated with adherence. Financial factors were not as commonly found to be related to access to HIV diagnosis and HIV treatment adherence, compared to knowledge of HIV-related risks and social support. CONCLUSION: The identification of persons who are less likely to test for HIV, and to adhere to HIV treatment, may serve as a guide for public health interventions, especially in resource-limited areas.

ICU Acquisition Rate, Risk Factors, and Clinical Significance of Digestive Tract Colonization With Extended-Spectrum Beta-Lactamase-Producing Enterobacteriaceae: A Systematic Review and Meta-Analysis.

OBJECTIVE: To evaluate the acquisition rate, identify risk factors, and estimate the risk for subsequent infection, associated with the colonization of the digestive tract with extended-spectrum beta-lactamase-producing Enterobacteriaceae during ICU-hospitalization. DATA SOURCES: PubMed, EMBASE, and reference lists of all eligible articles. STUDY SELECTION: Included studies provided data on ICU-acquired colonization with extended-spectrum beta-lactamase-producing Enterobacteriaceae in previously noncolonized and noninfected patients and used the double disk synergy test for extended-spectrum beta-lactamase-producing Enterobacteriaceae phenotypic confirmation. Studies reporting extended-spectrum beta-lactamase-producing Enterobacteriaceae outbreaks or data on pediatric population were excluded. DATA EXTRACTION: Two authors independently assessed study eligibility and performed data extraction. DATA SYNTHESIS: Thirteen studies (with 15,045 ICUs-patients) were evaluated using a random-effect model and a meta-regression analysis. The acquisition rate of digestive tract colonization during ICU stay was 7% (95% CI, 5-10) and it varies from 3% (95% CI, 2-4) and 4% (95% CI, 2-6) in the Americas and Europe to 21% (95% CI, 9-35) in the Western Pacific region. Previous hospitalization (risk ratio, 1.57 [95% CI, 1.07-2.31]) or antibiotic use (risk ratio, 1.65 [95% CI, 1.15-2.37]) and exposure to beta-lactams/beta-lactamase inhibitors (risk ratio, 1.78 [95% CI, 1.24-2.56]) and carbapenems (risk ratio, 2.13 [95% CI, 1.49-3.06]) during the ICU stay were independent risk factors for ICU-acquired colonization. Importantly, colonized patients were more likely to develop an extended-spectrum beta-lactamase-producing Enterobacteriaceae infection (risk ratio, 49.62 [95% CI, 20.42-120.58]). The sensitivity and specificity of prior colonization to predict subsequent extended-spectrum beta-lactamase-producing Enterobacteriaceae infection were 95.1% (95% CI, 54.7-99.7) and 89.2% (95% CI, 77.2-95.3), respectively. CONCLUSIONS: The ICU acquisition rate of extended-spectrum beta-lactamase-producing Enterobacteriaceae ranged from 5% to 10%. Previous use of beta-lactam/beta-lactamase or carbapenems and recent hospitalization were independent risk factors for extended-spectrum beta-lactamase-producing Enterobacteriaceae colonization, and colonization was associated with significantly higher frequency of extended-spectrum beta-lactamase-producing Enterobacteriaceae subsequent infection and increased mortality.

Colonisation with extended-spectrum ß-lactamase-producing Enterobacteriaceae and risk for infection among patients with solid or haematological malignancy: a systematic review and meta-analysis.

Cancer patients are vulnerable to infections, including those with extended-spectrum ß-lactamase-producing Enterobacteriaceae (ESBL-PE), and most of these infections are associated with colonisation of the gastrointestinal tract. The aim of this study was to estimate the prevalence of gastrointestinal colonisation with ESBL-PE cancer populations and to determine the risk for subsequent bloodstream infection (BSI) with these pathogens. PubMed and EMBASE databases were searched from 1 January 1991 to 1 March 2016 to identify studies regarding ESBL-PE colonisation among patients with malignancies. Ten studies (out of 561 non-duplicate articles) were included, providing data on 2211 patients. The pooled prevalence of ESBL-PE colonisation was 19% [95% confidence interval (CI) 8-32%]. Stratifying per region, the pooled prevalence in Europe was 15% (95% CI 10-21%), whereas in Asia the pooled prevalence was 31% (95% CI 4-69%). In addition, the pooled prevalence was 15% (95% CI 7-24%) among patients with haematological malignancy, whereas no studies were identified that included solely patients with solid tumours. Notably, cancer patients with ESBL-PE colonisation were 12.98 times (95% CI 3.91-43.06) more likely to develop a BSI with ESBL-PE during their hospitalisation compared with non-colonised patients. We found that, overall, one in five patients with cancer is colonised with ESBL-PE and the incidence can be as high as one in three in Asia. This is important because colonisation was associated with an almost 13 times higher risk for developing BSI with ESBL-PE. Screening measures should be evaluated to identify their clinical benefit in patients with malignancy.

The Impact of Shortages on Medication Prices: Implications for Shortage Prevention.

BACKGROUND: Medication shortages are frequent and have clinical and financial ramifications; however, their effect on drug prices remains unknown. OBJECTIVE: To examine price progression of medications affected by a shortage. METHODS: We collected prices of medications covered under Medicare Part B, reflective of general market prices, and data on clinically relevant shortages for the period 2005-16. We used linear mixed-effects models to examine the price growth of affected medications. RESULTS: Shortage medications demonstrated a quarterly price growth of -0.5 % (95 % confidence interval [CI] -1.6, 0.6) in the period preceding a shortage, 4.3 % (95 % CI 3.6, 4.5) during a shortage, and 4.1 % (95 % CI 2.6, 5.5) in the post-shortage period. Medications not affected by a shortage had a quarterly price growth of 0.2 % (95 % CI -0.3, 0.6). CONCLUSIONS: Medication shortages are associated with price increases, and these increases are likely reactive to the low profitability of the affected medications and thus, proactive collaboration between the US Food and Drug Administration and industry can serve to identify low-profit drugs and evaluate measures to ensure continued production.

Prevalence of ESBL-producing Enterobacteriaceae in paediatric urinary tract infections: A systematic review and meta-analysis.

OBJECTIVES: We aimed to evaluate the prevalence of paediatric urinary tract infections (UTIs) caused by extended spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-PE), identify predisposing factors and examine their effect on the length of hospital stay (LOS). METHODS: For this systematic review and meta-analysis, we searched the PubMed and EMBASE databases for studies that provide data on the rate of ESBL-PE among paediatric UTIs. RESULTS: Out of 1828 non-duplicate citations, 16 studies reporting a total of 7374 cases of UTI were included. The prevalence of ESBL-PE was 14% [(95%CI 8, 21)]. Vesicoureteral reflux (VUR) [OR = 2.79, (95%CI 1.39, 5.58)], history of UTI [OR = 2.89 (95%CI 1.78, 4.68)] and recent antibiotic use [OR = 3.92, (95%CI 1.76, 8.7)] were identified as risk factors. The LOS was significantly longer among children infected with ESBL-PE, compared to those infected with other uropathogens. [SMD = 0.88, (95%CI 0.40, 1.35)]. CONCLUSIONS: In the paediatric population, 1 out of 7 UTIs are caused by ESBL-PE. Patients with VUR, previous UTI or recent antibiotic use constitute a high risk group and these pathogens are associated with increased LOS. The significant incidence of ESBL-PE in this population should be taken into consideration in the development of empiric treatment protocols and antibiotic stewardship programmes, especially in high-prevalence areas.

National income inequality and declining GDP growth rates are associated with increases in HIV diagnoses among people who inject drugs in Europe: a panel data analysis.

BACKGROUND: There is sparse evidence that demonstrates the association between macro-environmental processes and drug-related HIV epidemics. The present study explores the relationship between economic, socio-economic, policy and structural indicators, and increases in reported HIV infections among people who inject drugs (PWID) in the European Economic Area (EEA). METHODS: We used panel data (2003-2012) for 30 EEA countries. Statistical analyses included logistic regression models. The dependent variable was taking value 1 if there was an outbreak (significant increase in the national rate of HIV diagnoses in PWID) and 0 otherwise. Explanatory variables included the growth rate of Gross Domestic Product (GDP), the share of the population that is at risk for poverty, the unemployment rate, the Eurostat S80/S20 ratio, the Gini coefficient, the per capita government expenditure on health and social protection, and variables on drug control policy and drug-using population sizes. Lags of one to three years were investigated. FINDINGS: In multivariable analyses, using two-year lagged values, we found that a 1% increase of GDP was associated with approximately 30% reduction in the odds of an HIV outbreak. In GDP-adjusted analyses with three-year lagged values, the effect of the national income inequality on the likelihood of an HIV outbreak was significant [S80/S20 Odds Ratio (OR) = 3.89; 95% Confidence Interval (CI): 1.15 to 13.13]. Generally, the multivariable analyses produced similar results across three time lags tested. INTERPRETATION: Given the limitations of ecological research, we found that declining economic growth and increasing national income inequality were associated with an elevated probability of a large increase in the number of HIV diagnoses among PWID in EEA countries during the last decade. HIV prevention may be more effective if developed within national and European-level policy contexts that promote income equality, especially among vulnerable groups.

Field application of SD bioline malaria Ag Pf/Pan rapid diagnostic test for malaria in Greece.

Greece, a malaria-free country since 1974, has experienced re-emergence of Plasmodium vivax autochthonous malaria cases in some agriculture areas over the last three years. In early 2012, an integrated control programme (MALWEST Project) was launched in order to prevent re-establishment of the disease. In the context of this project, the rapid diagnostic tests (RDT) of SD Bioline Malaria Ag Pf/Pan that detects hrp-2 and pan-LDH antigens were used. The aim of this study was to assess the field application of the RDT for the P. vivax diagnosis in comparison to light microscopy and polymerase chain reaction (PCR). A total of 955 samples were tested with all three diagnostic tools. Agreement of RDT against microscopy and PCR for the diagnosis of P. vivax was satisfactory (K value: 0.849 and 0.976, respectively). The sensitivity, specificity and positive predictive value of RDT against PCR was 95.6% (95% C.I.: 84.8-99.3), 100% (95% C.I.: 99.6-100.0) and 100% (95% CI: 91.7-100.0) respectively, while the sensitivity, specificity and positive predictive value of RDT against microscopic examination was 97.4% (95% C.I.: 86.1-99.6), 99.4% (95% C.I.: 98.6-99.8) and 86.1% (95% CI: 72.1-94.7), respectively. Our results indicate that RDT performed satisfactory in a non-endemic country and therefore is recommended for malaria diagnosis, especially in areas where health professionals lack experience on light microscopy.

Laboratory and surveillance studies following a suspected Dengue case in Greece, 2012.

OBJECTIVES: To describe the laboratory assays used to investigate a suspected dengue case in summer 2012 in western Greece and to report the public health response. DESIGN OF METHODS: Samples from the patient were tested for detection of Dengue virus (DENV) antibodies, NS1 antigen and RNA. Public health professionals interviewed residents of the village, and blood samples taken from 132 persons were tested for antibodies for DENV and West Nile virus (WNV). Samples from 10 persons who reported symptoms in the prior 15 days (including 3 persons who had fever at the time of sampling) were tested for DENV, WNV and additional arboviruses. Entomological missions were organized in the area of potential exposure to investigate the presence of competent DENV vectors. RESULTS: Based on a combination of serological and molecular methods, DENV infection was excluded, and the problems in the serology, especially in the DENV NS1 antigen, were attributed to interfering factors. A 6.1% WNV seroprevalence was detected in the region, and phlebovirus IgM and IgG antibodies were detected in two of three persons who had fever at the time of sampling. Aedes albopictus adult mosquitoes were present in the region. CONCLUSIONS: A multi-disciplinary field and laboratory investigation showed no evidence of DENV infection. There is a need for industries to improve the immunometric assays to avoid interference with rheumatoid or other factors, and increased awareness is needed for the evaluation of the diagnostic assays. The high WNV seroprevalence in the investigated region highlights the need for strengthening awareness on vector borne diseases. The presence of Ae. albopictus suggests that the possibility of introduction of DENV exists, and preparedness plans are needed.

Laboratory and clinical characteristics of human West Nile virus infections during 2011 outbreak in southern Greece.

During the summer-autumn of 2011, a human outbreak of West Nile virus (WNV) infection occurred in southern Greece, following the first outbreak during 2010 in northern Greece. An investigation was performed to analyze laboratory diagnosis, geographic distribution, and clinical features of WNV cases in southern Greece. Serum and cerebrospinal fluid (CSF) specimens from all patients seeking laboratory diagnosis for suspected WNV infection were tested for the presence of specific WNV immunoglobulin M (IgM) and IgG antibodies. Detection of WNV RNA in CSF and whole blood samples was accomplished by real-time PCR. During August-October of 2011, 31 confirmed or probable cases of WNV infection were identified. In 25 of them, individuals experienced severe neurological manifestations and were classified as WNV neuroinvasive disease cases. Risk factors such as advanced age, hypertension, and diabetes mellitus were identified in most cases with neurological complications. As many as 25 of the WNV cases occurred in the broader region of Athens; the majority of them (17 cases) were identified in municipalities of Eastern Attica, located almost 40 km from the metropolitan area of Athens and 500 km from Central Macedonia, where the 2010 WNV outbreak occurred. The spread of the virus in a newly affected area of the country suggests that WNV has been established in Greece and disease transmission will be continued in the future.

Greek NHS capacity constraints regarding intravenous treatment for rheumatoid arthritis patients.

Intravenous (iv) infusion of biologic agents is a highly effective therapeutic option for active rheumatoid arthritis (RA). In Greece, it is mandatory that all infusions are administered in a hospital setting; therefore, they are strongly correlated with the system's capacity in terms of resources. The objective of this paper was to assess the capacity of the Greek National Health System (NHS) hospitals to meet current/projected demand for iv treatment of RA patients. Semi-qualitative interviews on the basis of a strictly structured questionnaire were conducted with the Heads of all NHS RA infusion sites to record available resources, service utilization and ability to meet current/projected demand. Out of 31 NHS infusion sites, 28 responded (90.3%). On average, 41.6% of Greek NHS RA patients are treated with a biologic agent and 61.5% of respondents stated that available resources are insufficient to meet current demand. The most important constraints in selection order were as follows: space (93%), staff (89.5%), equipment (61.5%) and working hours (57%). Fifty-six percent of respondents stated that they may decline treatment to patients due to constraints. Overall, respondents estimated that the number of iv patients could be increased by 104%, were there no capacity constraints. An important proportion of the estimated 40.000 RA patients in Greece, for whom iv biologic treatment in the hospital setting is essential for disease control, may be declined treatment due to constraints in RA-specific resources. Rationalization and reallocation of NHS resources is required to ensure equity in access to effective treatment for all RA patients.

Outbreak of West Nile virus infection in Greece, 2010.

During 2010, an outbreak of West Nile virus infection occurred in Greece. A total of 197 patients with neuroinvasive disease were reported, of whom 33 (17%) died. Advanced age and a history of heart disease were independently associated with death, emphasizing the need for prevention of this infection in persons with these risk factors.

Fatal cases associated with pandemic influenza A (H1N1) reported in Greece.

Between 18 May 2009 and 3 May 2010, a total of 149 fatal cases associated with pandemic influenza A (H1N1) were reported in Greece. Detailed case-based epidemiological information was available for the large majority of fatal cases. The time distribution follows an epidemic curve with a peak in the beginning of December 2009 and a second peak one month later. This is similar to that of laboratory confirmed cases and influenza-like illness cases from our sentinel surveillance system, with two weeks delay. The most commonly reported underlying conditions were chronic cardiovascular disease and immunosuppression, while the most frequently identified risk factor was obesity. These findings should be taken into consideration, when vaccination strategies are employed.

An outbreak of gastroenteritis linked to seafood consumption in a remote Northern Aegean island, February-March 2010.

INTRODUCTION: Raw seafood consumption has frequently been linked to gastroenteritis and Norovirus is a common cause. In February and March 2010, there was an increase cases of gastroenteritis on the remote island of Agios Efstratios in the Northern Aegean Sea, Greece. A massive increase in seafood consumption associated with a religious festival a few days prior to the outbreak suggested seafood as the vehicle of transmission. METHODS: An outbreak investigation team visited the island in order to document the outbreak and find epidemiological evidence for its source. The whole island was used as a cohort in the retrospective cohort study that was conducted. RESULTS: Sixty-four of the 181 participants reported having had symptoms of gastroenteritis, of which 34 were considered primary cases. People who consumed any raw seafood imported to the island were 21.5 times (95% CI: 8.95-51.8) more likely to develop symptoms of gastroenteritis in the 72 hours following exposure. Consumption of local seafood was not found to be a risk factor. CONCLUSION: Despite the lack of laboratory evidence, all four Kaplan's criteria were met and the outbreak was thought to have been caused by Norovirus. The outbreak investigation demonstrates epidemiological methods for use in a remote setting, where the means for laboratory and environmental investigation may be absent or limited.