Recommendations for respiratory syncytial virus surveillance at the national level.

Respiratory syncytial virus (RSV) is a common cause of acute lower respiratory tract infections and hospitalisations among young children and is globally responsible for many deaths in young children, especially in infants aged <6 months. Furthermore, RSV is a common cause of severe respiratory disease and hospitalisation among older adults. The development of new candidate vaccines and monoclonal antibodies highlights the need for reliable surveillance of RSV. In the European Union (EU), no up-to-date general recommendations on RSV surveillance are currently available. Based on outcomes of a workshop with 29 European experts in the field of RSV virology, epidemiology and public health, we provide recommendations for developing a feasible and sustainable national surveillance strategy for RSV that will enable harmonisation and data comparison at the European level. We discuss three surveillance components: active sentinel community surveillance, active sentinel hospital surveillance and passive laboratory surveillance, using the EU acute respiratory infection and World Health Organization (WHO) extended severe acute respiratory infection case definitions. Furthermore, we recommend the use of quantitative reverse transcriptase PCR-based assays as the standard detection method for RSV and virus genetic characterisation, if possible, to monitor genetic evolution. These guidelines provide a basis for good quality, feasible and affordable surveillance of RSV. Harmonisation of surveillance standards at the European and global level will contribute to the wider availability of national level RSV surveillance data for regional and global analysis, and for estimation of RSV burden and the impact of future immunisation programmes.

The clinical presentation, treatment and outcome of serologically confirmed paediatric Lyme disease in the Republic of Ireland over a 5-year period: a retrospective cohort study.

Lyme disease (LD) is the most common tick-borne illness in Europe. Population-based studies in European children are few. This study aimed to assess the incidence, clinical presentation, treatment and outcome of serologically confirmed paediatric LD in the Republic of Ireland over a 5-year period. A retrospective review of records from accredited laboratories performing Borrelia burgdorferi serological testing was undertaken. Proformas were distributed to clinicians of children and adolescents with positive Lyme serology. Data were requested regarding clinical presentation, treatment and outcome. Updated NICE guidelines were used to classify clinical cases. Serology testing for B. burgdorferi was performed on 2908 samples. Sixty-three (2.2%) children were two-tier positive, generating a crude annual incidence rate of 1.15/100,000. Proformas were returned for 55 (87%) and 47 met clinical and laboratory criteria for LD. Twenty-seven (57%) presented with non-focal symptoms (erythema migrans and/or influenza-like symptoms), and 20 (43%) with focal symptoms (cranial nerve involvement, 11; CNS involvement, 8; arthritis, 1). Median age at presentation was 8.2 (2.5-17.9) years. Seventeen (36%) acquired LD overseas. Twenty-five (83%) of the remaining 30 children acquired infection in the West/Northwest of Ireland. Full resolution of symptoms was reported in 97% of those with available data. Serologically confirmed LD in children is relatively rare in the Republic of Ireland. Ninety-eight percent of children tested were seronegative. Of the seropositive cases, 40% could have been diagnosed based on clinical findings alone. Neurological presentations (40%) were common. Full resolution of symptoms occurred in almost all (97%) where data were available.

Hepatitis E virus - key points for the clinical haematologist.

In recent years there has been a paradigm shift in our understanding of the epidemiology and clinical features of hepatitis E virus (HEV) infection. Once classically described as an acute hepatitis associated with waterborne outbreaks in areas of poor sanitation, HEV is now recognised to be endemic in Europe and is probably zoonotic in origin. Evidence for transfusion-transmitted HEV has prompted the introduction of blood donor screening in a number of countries, but the risk to the haematology patient from food sources remains. The aim of this review therefore, is to equip the clinical haematologist with the knowledge required to diagnose HEV infection and to aid decision-making in patient management. The article also provides information on addressing patient concerns about their risk of acquiring hepatitis E and how this risk can be mitigated.

Seroepidemiological and phylogenetic characterization of neurotropic enteroviruses in Ireland, 2005-2014.

Enteroviruses (EVs) are associated with a broad spectrum of clinical presentation, including aseptic meningitis (AM), encephalitis, hand, foot and mouth disease, acute flaccid paralysis, and acute flaccid myelitis. Epidemics occur sporadically and are associated with increased cases of AM in children. The present study describes the seroepidemiological analysis of circulating EVs in Ireland from 2005 to 2014 and phylogenetic characterization of echovirus 30 (E-30), enterovirus A71 (EV-A71), and enterovirus D68 (EV-D68). EV VP1 genotyping was applied to viral isolates and clinical samples, including cerebrospinal fluid (CSF), and those isolates that remained untypeable by neutralising anti-sera. An increase in AM cases from 2010 to 2014 was associated with an E-30 genogroup variant VII and sequences clustered phylogenetically with those detected in AM outbreaks in France and Italy. EV-D68 viral RNA was not detected in CSF samples and no neurological involvement was reported. Three EV-A71 positive CSF samples were identified in patients presenting with AM. A phylogenetic analysis of respiratory-associated EV-D68 and EV-A71 cases in circulation was performed to determine baseline epidemiological data. EV-D68 segregated with clades B and B(1) and EV-A71 clustered as subgenogroup C2. The EV VP1 genotyping method was more sensitive than neutralising anti-sera methods by virus culture and importantly demonstrated concordance between EV genotypes in faecal and CSF samples which should facilitate EV screening by less invasive sampling approaches in AM presentations.

Hepatitis C Virus Core Mutations Associated with False-Negative Serological Results for Genotype 3a Core Antigen.

Genetic characterization of the genotype 3a (GT3a) hepatitis C virus (HCV) core region from HCV core antigen (HCVcAg)-negative/RNA-positive cases and HCVcAg-positive/RNA-positive controls identified significant associations between the substitutions A48T and T49A/P and failure to detect HCVcAg (P < 0.05). Polymorphisms at residues 48 and 49 in the core protein are present across all major epidemic and endemic GTs. These findings have implications for HCV diagnosis, particularly in low-income regions in which GT3a HCV is endemic.

Pregnancy Outcomes of Mothers with Detectable CMV-Specific IgM Antibodies: A Three-Year Review in a Large Irish Tertiary Referral Maternity Hospital.

A retrospective audit was performed for all obstetric patients who had positive CMV IgM results between January 2012 and December 2014 in the Rotunda Hospital, Ireland. In total, 622 CMV IgM positive tests were performed on samples from 572 patients. Thirty-seven patients had a positive CMV IgM result (5.9%) on the Architect system as part of the initial screening. Three patients were excluded as they were not obstetric patients. Of the 34 pregnant women with CMV IgM positive results on initial screening, 16 (47%) had CMV IgM positivity confirmed on the second platform (VIDAS) and 18 (53%) did not. In the 16 patients with confirmed positive CMV IgM results, four (25%) had acute infection, two (12.5%) had infection of uncertain timing, and ten (62.5%) had infection more than three months prior to sampling as determined by the CMV IgG avidity index. Two of the four neonates of women with low avidity IgG had CMV DNA detected in urine. Both these cases had severe neurological damage and the indication for testing their mothers was because the biparietal diameter (BPD) was less than the 5th centile at the routine 20-week gestation anomaly scan.

Necrotizing fasciitis: The need for urgent surgical intervention and the impact of intravenous drug use.

BACKGROUND: Necrotizing fasciitis (NF) is a relatively rare infection of soft tissues. This study reviewed the epidemiology and pathophysiology of admissions to a tertiary referral hospital over a twelve year period comparing outcomes and findings with international norms and to identify potential areas of change to optimise outcomes. STUDY DESIGN: A retrospective review of patients diagnosed with NF from Jan 1st 1999 to Dec 31st 2011 was performed. Patient demographics, risk factors, operative procedures, microbiology results and outcomes were recorded. Comparative analysis was performed. RESULTS: 37 patients were admitted with NF, comprising 30 males and 7 females with a median age of 55 years. The most common site of infection was the perineum (51%). The overall mortality rate was 29% and was significantly associated with age greater than 60 years (p = 0.0018) and the presence of one or more risk factor (p = 0.0046). The number of surgical procedures ranged from one to fifteen with a median length of stay of 35.5 days. There was a significant increase in the number of admissions in 2009-2010 (p < 0.001), coinciding with the emergence of NF in intravenous drug users (IVDU). 43% of patients (n = 16/37) required skin grafting, which was significantly higher in the IVDU group (n = 5/6, p = 0.0232). CONCLUSIONS: Necrotizing fasciitis remains a significant life-threatening event. The diversity of causative pathogens emphasises the need for prompt microbiology/infectious diseases consultation. The increased occurrence within the IVDU cohort in this study highlights the need for a heightened level of clinical suspicion in these patients to prompt early surgical intervention.

Cytokine responses to Staphylococcus aureus bloodstream infection differ between patient cohorts that have different clinical courses of infection.

BACKGROUND: The clinical course of Staphylococcus aureus bloodstream infection is unpredictable and bacterial virulence, host immune response and patient characteristics are among the factors that contribute to the clinical course of infection. To investigate the relationship between cytokine response and clinical outcome, circulating cytokine levels were investigated in response to S. aureus bloodstream infection in patients with different clinical courses of infection. METHODS: A prospective study was carried out in 61 patients with S. aureus bloodstream infection and circulating levels of IL-6, GRO-γ, RANTES and leptin were assessed over the course of the infection. Levels were compared in patients with complicated courses of infection (e.g. infective endocarditis) versus uncomplicated courses of S. aureus bloodstream infection and methicillin-resistant S. aureus Vs methicillin-susceptible S. aureus infection. RESULTS: Significantly lower leptin levels (p < 0.05) and significantly higher IL-6 levels (p < 0.05) were detected at laboratory diagnosis in patients with complicated compared to uncomplicated S. aureus bloodstream infection. Significantly higher levels of GRO-γ were associated with MRSA infection compared to MSSA infection. CONCLUSIONS: IL-6 may be an early inflammatory marker of complicated S. aureus bloodstream infection. Leptin may be protective against the development of a complicated S. aureus bloodstream infection.

Detection of hepatitis E RNA in pork products at point of retail in Ireland - Are consumers at risk?

Hepatitis E (HEV), a zoonotic virus, is the leading cause of acute viral hepatitis in Europe. The presence of HEV in domestic pigs can result in infections in humans through consumption of pork products which are undercooked or where processing methods are insufficient to inactivate the virus. In Ireland, pork accounts for 34 % of all meat consumption (CSO, 2022) and the prevalence of HEV in products at point of retail has not previously been characterised. A sampling strategy was designed in which high pork content sausages, fresh pork liver and raw fermented sausages were systematically purchased from three types of retailers between May 2018 and March 2019. In total, 200 pork products were tested using a lysing agent to release the HEV from the product for detection. RT-PCR for HEV was performed on samples with an extraction efficiency >1 % (n = 188/200) (94 %). Low level HEV RNA was detected in 9/188 (4.8 %) pork products tested. The highest incidence of HEV RNA was in pork liver where 6/25 (24 %) samples were positive. The concentration of HEV ranged from 0.02 - to 9.4 genome copies/g of pork. Based on these data an exposure assessment was performed which found that if consumers followed advice from the Food Safety Authority of Ireland to achieve core temperatures of 70 °C or higher when cooking, the risk was likely to be negligible.

Detection of Hepatitis A RNA, Hepatitis E RNA, Human Adenovirus F DNA, and Norovirus RNA in Fresh and Frozen Berry Products at Point of Retail in Ireland.

Soft fruits are at particular risk of contamination with enteric viruses such as Hepatitis A virus (HAV), Hepatitis E Virus (HEV), Norovirus (NoV), Human Adenovirus (HAdV) and Sapovirus (SaV). The aim of this study was to investigate, for the first time, the presence of these biological agents in ready to eat (RTE) berries at point of retail in Ireland. A sampling strategy was designed in which RTE fresh and frozen strawberries and raspberries were purchased from five retailers between May and October 2018. Reverse Transcriptase Polymerase Chain Reaction (RT-qPCR) assays for HEV RNA, Nov RNA, SaV RNA, and human Adenovirus species F DNA (HAdV-F) were performed on 239 samples (25g portions). Viral nucleic acid was present in 6.7% (n = 16) of samples tested as follows: HAV RNA (n = 5), HAdV-F DNA (n = 5), HEV RNA (n = 3) and NoV GII RNA (n = 3). Sapovirus RNA was not detected in any product. No significant differences were found between berry type, fresh/frozen status, or supermarket source. This study suggests a risk that exists across all retail outlets however only low levels of nucleic acid ranging from 0 to 16 genome copies/g were present. Although these findings may reflect non-viable/non-infectious virus the continued provision of risk mitigation advice to consumers is warranted and further work is required to ensure control measures to reduce contamination are implemented and enforced.

An interpretation algorithm for molecular diagnosis of bacterial vaginosis in a maternity hospital using machine learning: proof-of-concept study.

Allplex Bacterial vaginosis assay (Seegene, South Korea) is a molecular test for bacterial vaginosis (BV). A machine learning algorithm was devised on 200 samples (BV = 23, non-BV = 177) converting 7 identified bacterial strains polymerase chain reaction results to binary output of BV detected or not. Comparing algorithm interpretation of molecular results to the consensus Gram stain (Hay's criteria), the sensitivity was 65% [95% confidence interval (CI) 42-83%], specificity was 98% (95% CI 95-99%), positive predictive value was 83% (95% CI 58-96%), and negative predictive value was 95% (91-98%) with area under the curve of 0.82 (95% CI 0.76-0.87). For the second phase, 100 samples were processed using the 2 techniques in parallel, with the scientists blinded to the result of the other method. There was agreement 90% of the cases (n = 90/100). The samples that were called BV by the algorithm but non-BV by Gram stain all cluster with the concordant BV samples, suggesting that the molecular test was correct.

Standardising surveillance of hepatitis E virus infection in the EU/EEA: A review of national practices and suggestions for the way forward.

BACKGROUND: Hepatitis E virus (HEV) infection is not notifiable at EU/EEA level, therefore surveillance relies on national policies only. Between 2005 and 2015, more than 20,000 cases were reported in EU/EEA countries. HEV testing is established in 26 countries and 19 countries sequence HEV viruses. OBJECTIVE AND STUDY DESIGN: WHO's European Action plan for viral hepatitis recommends harmonised surveillance objectives and case definitions. ECDC's HEV expert group developed minimal and optimal criteria for national hepatitis E surveillance to support EU/EEA countries in enhancing their capacity and to harmonise methods. RESULTS: The experts agreed that the primary objectives of national surveillance for HEV infections should focus on the basic epidemiology of the disease: to monitor the incidence of acute cases and chronic infections. The secondary objectives should be to describe viral phylotypes or subtypes and to identify potential clusters/outbreaks and possible routes of transmission. Seventeen of 20 countries with existing surveillance systems collect the minimal data set required to describe the epidemiology of acute cases. Eleven countries test for chronic infections. Twelve countries collect data to identify potential clusters/outbreaks and information on possible routes of transmission. DISCUSSION: Overall, the majority of EU/EEA countries collect the suggested data and meet the outlined requirements to confirm an acute case.

Complete Genome Sequence of a Human Sapovirus GI.2 Variant, Isolated from a Patient in Ireland in 2016.

We report here the first near-complete genome sequence (7,463 nucleotides) of a human sapovirus GI.2 variant from Dublin, Ireland, detected in an adult with gastroenteritis in 2016.

Low predictive value of positive transplant perfusion fluid cultures for diagnosing postoperative infections in kidney and kidney-pancreas transplantation.

AIMS: Infection following transplantation is a cause of morbidity and mortality. Perfusion fluid (PF) used to preserve organs between recovery and transplantation represents a medium suitable for the growth of microbes. We evaluated the relevance of positive growth from PF sampled before the implantation of kidney or kidney-pancreas (KP) allografts. METHODS: Between January 2007 and January 2011, 548 kidney/KP transplants were performed in our centre. A retrospective review of patient records with culture-positive PF was performed. RESULTS: PF was received from 483 (88%) patients, of which 35 (7%, 95% CI 5.3% to 9.9%) were positive for bacteria (31/483, 6.4%, 95% CI 4.6% to 9.8%) and fungi (4/483, 0.8%, 95% CI 0.3% to 2.1%). Thirty-two of the 35 culture-positive PF (91.4%, 95% CI 77.6% to 97%) were considered insignificant. The remaining three patients developed sepsis postoperatively, which was considered to be possibly related to growth in PF; Escherichia coli in one and Klebsiella pneumoniae in two. Of the non-skin flora bacteria cultured from PF, six were resistant to the prophylactic antibiotic given intraoperatively, but only one developed infection postoperatively (E coli, resistant to the co-amoxiclav). CONCLUSIONS: Significant attributable morbidity associated with PF-positive culture results was relatively rare. Culture of organisms other than Enterobacteriaceae or fungi are likely to represent contamination.

Nosocomial infections in a cohort of extracorporeal life support patients.

OBJECTIVES: To examine nosocomial infections in a cohort of patients receiving extracorporeal life support (ECLS) at our institution and to identify the types of infections, impact of prophylaxis, and any apparent risk factors for infection. METHODS: In a retrospective cohort study, we examined the records of all patients who received ECLS at our institution between August 2009 and March 2011. A prospective, daily, multidisciplinary assessment of all microbiological issues in these patients was carried out, including assessment of microbiological culture positivity and clinical evidence of infection. The results of these assessments were analysed in relation to HELICS (Hospital in Europe Link for Infection Control through Surveillance) and CDC (Centers for Disease Control and Prevention) diagnostic criteria. The use of antimicrobials in these patients was also assessed, as well as the overall bloodstream infection rate in ICU patients. RESULTS: Seventeen patients received ECLS during the study period, with a total of 445 ECLS days. Of these patients, 13 received respiratory (venovenous) ECLS and four received cardiac (venoarterial) ECLS. There were 17 infections in the cohort: 11 ventilator-associated pneumonias; four bloodstream infections (likely all catheter related, yielding a rate of 9.0 infections/1000 ECLS days); one skin and soft tissue infection; and one urinary tract infection. The bloodstream infection rate in the ICU population as a whole was 9.30/1000 bed-days in 2009 and 7.21/1000 bed-days in 2010. Resistant organisms were identified in 3/17 infections: one methicillin-resistant Staphylococcus aureus, one multidrug-resistant strain of Pseudomonas and one extended-spectrum Β-lactamase-producing Escherichia coli. The median time to acquiring nosocomial infection was 25 days (interquartile range, 13-33 days). The first four ECLS patients received antibacterial (vancomycin) and antifungal (caspofungin) prophylaxis for the duration of ECLS, whereas the later cohort of 13 did not. In patients who received prophylactic antimicrobials, the defined daily dose (DDD) per 100 ECLS days was 49.54 for vancomycin and 49.63 for meropenem. In patients who did not receive prophylaxis, the corresponding DDDs were 25.31 and 37.73, respectively. In ICU patients overall, the DDD per 100 bed-days over the same time period was 13.60 for vancomycin and 19.75 for meropenem. There were 21/445 ECLS days on which antimicrobials were not used. CONCLUSION: Although ECLS patients are at high risk of acquiring nosocomial infections, the infection rate in our cohort was low. The bloodstream infection rate compared favourably with previously published rates, and was comparable with the bloodstream infection rate among ICU patients as a whole over the same time period. Increased duration of ECLS in this cohort may correlate with an increased rate of infection, consistent with data from other ECLS centres. Antimicrobial use in ECLS patients was high relative to overall use in ICU patients. Larger studies are warranted to evaluate the diagnosis, treatment and overall approach to managing nosocomial infection in ECLS patients.