Comparison of diagnostic clinical samples and environmental sampling for enterovirus and parechovirus surveillance in Scotland, 2010 to 2012.

Human enteroviruses (EV) and parechoviruses (HPeV) within the family Picornaviridae are the most common causes of viral central nervous system (CNS)-associated infections including meningitis and neonatal sepsis-like disease. The frequencies of EV and HPeV types identified in clinical specimens collected in Scotland over an eight-year period were compared to those identified in sewage surveillance established in Edinburgh. Of the 35 different EV types belonging to four EV species (A to D) and the four HPeV types detected in this study, HPeV3 was identified as the most prevalent picornavirus in cerebrospinal fluid samples, followed by species B EV. Interestingly, over half of EV and all HPeV CNS-associated infections were observed in young infants (younger than three months). Detection of species A EV including coxsackievirus A6 and EV71 in clinical samples and sewage indicates that these viruses are already widely circulating in Scotland. Furthermore, species C EV were frequently identified EV in sewage screening but they were not present in any of 606 EV-positive clinical samples studied, indicating their likely lower pathogenicity. Picornavirus surveillance is important not only for monitoring the changing epidemiology of these infections but also for the rapid identification of spread of emerging EV and/or HPeV types.

Use of laboratory-based surveillance data to estimate the number of people chronically infected with hepatitis B living in Scotland.

It is paramount to understand the epidemiology of chronic hepatitis B to inform national policies on vaccination and screening/testing as well as cost-effectiveness studies. However, information on the national (Scottish) prevalence of chronic hepatitis B by ethnic group is lacking. To estimate the number of people with chronic hepatitis B in Scotland in 2009 by ethnicity, gender and age, the test data from virology laboratories in the four largest cities in Scotland were combined with estimates of the ethnic distribution of the Scottish population. Ethnicity in both the test data and the Scottish population was derived using a name-based ethnicity classification software (OnoMAP; Publicprofiler Ltd, UK). For 2009, we estimated 8720 [95% confidence interval (CI) 7490-10 230] people aged ⩾15 years were living with chronic hepatitis B infection in Scotland. This corresponds to 0·2% (95% CI 0·17-0·24) of the Scottish population aged ⩾15 years. Although East and South Asians make up a small proportion of the Scottish population, they make up 44% of the infected population. In addition, 75% of those infected were aged 15-44 years with almost 60% male. This study quantifies for the first time on a national level the burden of chronic hepatitis B infection by ethnicity, gender and age. It confirms the importance of promoting and targeting ethnic minority groups for hepatitis B testing.

Increased reports of Mycoplasma pneumoniae from laboratories in Scotland in 2010 and 2011 - impact of the epidemic in infants.

In common with reports from other European countries, we describe a substantial increase in the number of laboratory reports of Mycoplasma pneumoniae in Scotland in 2010 and 2011. The highest number of reports came from those aged one year and younger. However, reports from young children were more likely to come from PCR testing than serological testing.

High detection frequency and viral loads of human rhinovirus species A to C in fecal samples; diagnostic and clinical implications.

Human rhinoviruses (HRVs) can be divided into three species; HRV-A to HRV-C. Up to 148 different HRV (sero)types have been identified to date. Because of sequence similarity between 5'-NCR of HRVs and enteroviruses (EVs), it is problematic to design EV-specific RT-PCR assays. The aims of this study were to assess the rate of false-detection of different rhinoviruses by EV RT-PCR, and to evaluate the diagnostic and clinical significance of such cross-reactivity. In vitro RNA transcripts of HRV A-C created from cDNA templates were quantified spectrophotometrically. Six hundred twenty-one stool samples screened as part of routine diagnostic for EV, 17 EV-positive stool samples referred for typing, 288 stool samples submitted for gastroenteritis investigations, and 1,500 CSF samples were included in the study. EV-specific RT-PCR detected RNA transcripts of HRV-A1b, HRV-B14, and HRV-Crpat18 but with 10-1,000 reduced sensitivity compared to EV transcripts. Screening fecal samples by EV RT-PCR identified 13 positive samples identified subsequently as rhinoviruses; a further 26 HRV-positive samples were identified by nested HRV RT-PCR. All individuals were hospitalized and presented mostly with diarrhea. A total of 26 HRV types were identified (HRV-A: 46%; HRV-B: 13%; HRV-C: 41%). Results confirm that EV-specific RT-PCR can detect HRVs, and at a practical level, identify potential problems of interpretation if fecal samples are used for surrogate screening in cases of suspected viral meningitis. High detection frequencies (10%) and viral loads in stool samples provide evidence for enteric replication of HRV, and its association with enteric disease requires further etiological studies.

Population exposure to a novel influenza A virus over three waves of infection.

BACKGROUND: The influenza A(H1N1)2009 virus has been spreading throughout the world since April 2009. Since then, several studies have been undertaken to measure the frequency of antibodies that react against the virus. Microneutralisation assays have regularly been used for these analyses, and titres of ≥40 have conventionally been taken to represent significant levels of antibodies (this significance is derived from it being four times the minimum level of antibodies that the assay can detect rather an established correlate of protection). However a microneutralisation titre that correlates with protection against influenza A(H1N1)2009 has not been established. OBJECTIVES: Analysing influenza A(H1N1)2009 antibody seroprevalence in Scotland at multiple timepoints, and in different age groups and geographical locations, and comprehensively describing the spread of the virus in Scotland (taken alongside previously published data). This study presents for the first time the effects of a novel influenza virus on a naïve population that has been followed from the initial outbreak to a time when the majority of the population have reactive antibodies. STUDY DESIGN: A microneutralisation titre ≥10 represents the minimum level of antibodies detectable by the assay. Blood samples (taken in April 2009 and April 2010 in Edinburgh (n=400 each year), and in February 2011 in Aberdeen, Edinburgh, Glasgow, and Inverness (n=1600)) were tested for the presence of influenza A(H1N1)2009 antibodies at this titre. This represents an effective indicator of the proportion of a population who have been exposed to the virus. RESULTS: Following the 2010/2011 influenza season, there is evidence of exposure to influenza A(H1N1)2009 in approximately four fifths of the Scottish population. CONCLUSIONS: This study provides impetus to the call for further research in establishing robust correlates of susceptibility to influenza infection and the development of clinical illness, provides useful information for future outbreaks, and is relevant to public health policy in planning for future influenza seasons.

Influenza A(H1N1)2009 antibody seroprevalence in Scotland following the 2010/11 influenza season.

Following the 2010/11 influenza season, we determined the age- and location-specific seroprevalence of antibodies against the influenza A(H1N1)2009 virus in Scotland. Samples were analysed by microneutralisation assay. Age/seropositivity profiles varied significantly between cities. The increases in seroprevalence relative to the previous influenza season (2009/10) were similar across age groups and geographic locations. However, the increased seropositivity in older adults appeared to be driven by exposure to vaccination, indicating significantly lower levels of infection than in younger age groups.

2009 pandemic influenza A(H1N1) virus in Scotland: geographically variable immunity in Spring 2010, following the winter outbreak.

We determined the age- and location-specific seroprevalence of antibodies against 2009 pandemic influenza A(H1N1) virus in Scotland following the first two waves of infection. Serum samples collected following the winter outbreak were analysed by microneutralisation assay. The proportion of positive sera varied significantly between cities and, in the case of Inverness, between age groups (with younger adults more likely to be positive than older individuals). This study demonstrates that older people are no longer more likely to have antibodies against the virus than younger adults.

Hepatitis C virus infection among injecting drug users in Scotland: a review of prevalence and incidence data and the methods used to generate them.

It is estimated that of 50,000 persons in Scotland (1% of the county's population), infected with the hepatitis C virus (HCV), around 90% injected drugs. This paper reviews data on the prevalence and incidence of HCV, and the methods used to generate such information, among injecting drug users (IDUs), in Scotland. The prevalence estimate for HCV among IDUs in Scotland as a whole (44% in 2000), is comparable with those observed in many European countries. Incidence rates ranged from 11.9 to 28.4/100 person-years. The data have shaped policy to prevent infection among IDUs and have informed predictions of the number of HCV-infected IDUs who will likely progress to, and require treatment and care for, severe HCV-related liver disease. Although harm reduction interventions, in particular needle and syringe exchanges and methadone maintenance therapy, reduced the transmission of HCV among IDUs during the early to mid-1990s, incidence in many parts of the country remains high. The prevention of HCV among IDUs continues to be one of Scotland's major public health challenges.

Use of genomic analysis of varicella-zoster virus to investigate suspected varicella-zoster transmission within a renal unit.

BACKGROUND: The source of hospital-acquired chickenpox infection may be presumed from a known exposure, but has not been previously proven using genomic analysis. OBJECTIVE: Investigation of suspected VZV transmission was done using single nucleotide polymorphism genomic analysis. STUDY DESIGN: Comparison was made of viral isolates from two patients with chickenpox on the same ward who were not known to have had direct contact. RESULTS: An identical genotype in the variable R1 region of the VZV was isolated from the two patients. CONCLUSION: Inapparent hospital-acquired transmission was the most likely route of infection.

Hepatitis A virus and injecting drug misuse in Aberdeen, Scotland: a case-control study.

To describe an epidemiological investigation of an outbreak of hepatitis A virus (HAV) infection among injecting drug users in Aberdeen, Scotland. A case-control study to determine whether transmission was facilitated by poor personal hygiene or through sharing injecting equipment. Cases were more likely to report not washing their hands after using the toilet [odds ratio (OR) = 12.9, 95% confidence interval (CI) = 1.58-105.89] or before preparing food (OR = 4.0, 95% CI = 1.01-15.8), and less likely to have washed their hands prior to preparing drugs (OR = 10.67, 95% CI = 2.14-53.07). Cases were also more likely to report recipient sharing of needles/syringes (OR = 8.27, 95% CI = 1.68-40.57), and to have had injecting contact with someone who was jaundiced (OR = 29.4, 95% CI = 3.18-271.44). The results indicate that the lack of hygiene within the context of individuals gathering to prepare and inject drugs provides ample opportunity for the transmission of HAV. Although the promotion of good hygiene and the avoidance of sharing injecting equipment are important measures in preventing HAV transmission, they are unlikely to effect major behavioural change. Such measures should, therefore, be reinforced by routinely offering HAV vaccine to injectors.

Increasing incidence of acute hepatitis B virus infection referrals to the Aberdeen Infection Unit: a matter for concern.

OBJECTIVES: To assess the epidemiology and clinical outcomes of acute hepatitis B virus (HBV) infections presenting to a regional Infection Unit over a ten year period--with reference to the issues of injection drug use and strategies aimed at reducing transmission, notably needle exchange and immunisation programmes. METHODS: A retrospective casenote review of all patients with acute HBV managed at the Infection Unit in Aberdeen between 1991-2000. RESULTS: One hundred and nineteen (119) patients with acute HBV infection were managed during the period of review. The annual number of patients increased from a mean of 3.3/year during the years 1991-96 to 46 in 2000. The risk factors associated with HBV infection were being an injection drug user (IDU) in 57 (47.9%), heterosexual sex in 22 (18.5%), sex with an IDU in 4 (3.4%), men who had sex with men in 10 (8.4%), tattooing in 1 (0.8%), a needle stick injury in 1 (0.8%), trauma 1 (0.8%) and unknown in 23 (19.3%). Many of these patients had "dabbled" in drug use. Thirty-one (54.4%) of the IDU patients had previously been hospitalised with drug-related medical problems. Eighteen (31.6%) of the IDUs were receiving methadone at the time of presentation. CONCLUSIONS: There is an epidemic of HBV infection in the Grampian region of Scotland currently. Forty-six (65.7%) of the 70 infected patients diagnosed during 2000 were seen at the Infection Unit. The remainder had mild or asymptomatic disease and were managed in the community. This epidemic has occurred despite extensive use of local needle exchange facilities and might reflect missed opportunities to immunise IDUs against HBV infection. A co-ordinated approach is now in place to immunise IDUs and other high-risk groups, but the use of universal immunisation demands consideration.

Establishment of a database of diagnosed HCV-infected persons in Scotland.

To provide a comprehensive understanding of the epidemiology of hepatitis C virus (HCV) infection in Scotland, a database of all persons known to have been infected with HCV in Scotland was established. Non-identifying data, held on the computers and requests forms in Scotland's principal and confirmatory HCV testing laboratories, were entered onto a National Database at the Scottish Centre for Infection and Environmental Health. As at December 2001, records from 13,519 persons in Scotland known to have been infected with HCV had been entered on to the database (one in 378 of Scotland's population). Of the 13,519, 69% were male and 90% of the 9,092 for whom risk factor information was available had injected drugs; 37% were from Greater Glasgow. Fifty-six per cent of the 13,519 were diagnosed between 1998 and 2001; 1,727 (23%) of the new diagnoses from 1998 to 2001 were aged under 25 years. The data provide an insight into the epidemiology of HCV infection in Scotland. They support other data, which indicate that the current major risk factor for HCV in the country is injecting drug use.

Rotavirus gastroenteritis and central nervous system (CNS) infection: characterization of the VP7 and VP4 genes of rotavirus strains isolated from paired fecal and cerebrospinal fluid samples from a child with CNS disease.

Rotavirus RNA was detected in the cerebrospinal fluid (CSF) of a child with central nervous system disease symptoms associated with rotavirus gastroenteritis. The rotavirus isolates from the fecal and CSF samples were genotyped as G1P[8]. Sequence analysis of the VP7 and VP4 proteins derived from the fecal and CSF samples were remarkably similar to each other and to G1P[8] rotavirus strains commonly circulating in the community and associated with gastroenteritis.

Prevalence of hepatitis C among injectors in Scotland 1989-2000: declining trends among young injectors halt in the late 1990s.

We previously reported a continual decline in anti-HCV prevalence among young injectors from Glasgow and Lothian between 1990 and 1997. The original study was extended to ascertain if the anti-HCV prevalence among injectors from Glasgow, Lothian, Tayside and Grampian had changed since 1997. Residual sera from injectors who had undergone attributable anti-HIV testing were tested anonymously for anti-HCV. In all four regions, no significant changes in prevalence were found among those aged < 25 years during the late 1990s (Glasgow 1997-9/00: 43%-41%; Lothian 1997-9: 13%-17%; Tayside 1997-9: 45%-35%; Grampian 1996-9: 28%-29%). Among those aged > or = 25 years, significant decreases in prevalence were only observed in Glasgow (1997-9/00: 79%-72%, P = 0.03) and Lothian (1997-9: 54%-45%, P = 0.05). The findings highlight that existing harm reduction measures, acknowledged as having helped to reduce the spread of HCV, are not sufficient to bring this epidemic under control and reduce transmission to sporadic levels.

Hepatitis C virus among genitourinary clinic attenders in Scotland: unlinked anonymous testing.

Our objective is to gauge the prevalence of hepatitis C virus (HCV) antibodies among a population at risk of contracting sexually transmitted infections (STIs) and, thus, the efficiency with which the virus is transmitted sexually. The investigators undertook an unlinked anonymous HCV antibody testing study of residual syphilis serology specimens taken from attenders of genitourinary clinics in Glasgow, Edinburgh and Aberdeen during 1996/97. The results were linked to non-identifying risk information. Anti-HCV prevalences among non-injecting heterosexual men and women, and non-injecting homosexual/bisexual males ranged between 0 and 1.2%; the only exception to this was a 7.7% (4/52) prevalence among homosexual/bisexual males in Aberdeen. The overall anti-HCV prevalence for homosexual/bisexual males was 0.6% (4/668), for heterosexual males 0.8% (32/4135), for heterosexual females 0.3% (10/3035) and for injecting drug users 49% (72/148). Only 3 (all female) of the 46 non-injectors who were antibody positive were non-UK nationals or had lived abroad. HCV antibody positive injectors were less likely to have an acute STI and more likely to know their HCV status than non-injectors; no differences in these parameters were found between positive and negative non-injectors on anonymous HCV antibody testing. Our findings are in keeping with the prevailing view that HCV can be acquired through sexual intercourse but, for most people, the probability of this occurring is extremely low. Interventions to prevent the spread of HCV should be targeted mainly at injecting drug user (IDU) populations.

Sight-threatening varicella zoster virus infection after fludarabine treatment.

Varicella zoster virus (VZV) infection involving the posterior segment of the eye after fludarabine treatment has not previously been described. Two patients, who had completed fludarabine treatment 3 and 18 months previously, presented with visual loss that had been preceded by a recent history of cutaneous zoster. The use of the polymerase chain reaction (PCR) for VZV DNA from ocular specimens allowed rapid confirmation of clinical diagnosis and treatment with a good outcome in one patient. With the increasing use of fludarabine and other purine analogues, an awareness of such complications is important because of their potentially sight-threatening consequences.