Pamela Molyneaux

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 countys 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 Scotlands major public health challenges.

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.

Recombination of Globally Circulating Varicella Zoster Virus

ABSTRACT Varicella-zoster virus (VZV) is a human herpesvirus, which during primary infection typically causes varicella (chicken pox) and establishes lifelong latency in sensory and autonomic ganglia. Later in life, the virus may reactivate to cause herpes zoster (HZ; also known as shingles). To prevent these diseases, a live-attenuated heterogeneous vaccine preparation, vOka, is used routinely in many countries worldwide. Recent studies of another alphaherpesvirus, infectious laryngotracheitis virus, demonstrate that live-attenuated vaccine strains can recombine in vivo, creating virulent progeny. These findings raised concerns about using attenuated herpesvirus vaccines under conditions that favor recombination. To investigate whether VZV may undergo recombination, which is a prerequisite for VZV vaccination to create such conditions, we here analyzed 115 complete VZV genomes. Our results demonstrate that recombination occurs frequently for VZV. It thus seems that VZV is fully capable of recombination if given the opportunity, which may have important implications for continued VZV vaccination. Although no interclade vaccine-wild-type recombinant strains were found, intraclade recombinants were frequently detected in clade 2, which harbors the vaccine strains, suggesting that the vaccine strains have already been involved in recombination events, either in vivo or in vitro during passages in cell culture. Finally, previous partial and complete genomic studies have described strains that do not cluster phylogenetically to any of the five established clades. The additional VZV strains sequenced here, in combination with those previously published, have enabled us to formally define a novel sixth VZV clade. IMPORTANCE Although genetic recombination has been demonstrated to frequently occur for other human alphaherpesviruses, herpes simplex viruses 1 and 2, only a few ancient and isolated recent recombination events have hitherto been demonstrated for VZV. In the present study, we demonstrate that VZV also frequently undergoes genetic recombination, including strains belonging to the clade containing the vOKA strain.

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

Summary.  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.

Rise in testing and diagnosis associated with Scotland's Action Plan on Hepatitis C and introduction of dried blood spot testing

Background A key aim of the Hepatitis C Action Plan for Scotland was to reduce the undiagnosed population through awareness-raising activities, for general practitioners and those at risk, and the introduction of dried blood spot (DBS) sampling in community drug services to overcome barriers to testing. This study evaluates the impact of these activities on testing and diagnosis. Methods Data on hepatitis C virus (HCV) testing undertaken between January 1999 and December 2011 in Scotlands four largest health boards were analysed. Segmented regression analysis was used to examine changes in testing following the (1) launch of the Action Plan and (2) introduction of DBS testing. Results Between the pre-Action Plan and Action Plan periods, increases were observed in the average number of HCV tests (19 058–29 045), positive tests (1993–2405) and new diagnoses (1221–1367). Since July 2009, 26% of new diagnoses were made in drug services. The trend in the number of positive tests was raised during the Action Plan, compared to pre-Action Plan, particularly in drug services (rate ratio (RR)=1.4, p<0.001) and prisons (RR=1.2, p<0.001); no change was observed in general practice. Following introduction of DBS testing, there was a 3-fold increase in testing (RR=3.5, p<0.001) and 12-fold increase in positives (RR=12.1, p<0.001) in drug services. Conclusions The introduction of DBS sampling in community drug services has made an appreciable contribution to efforts to diagnose the HCV-infected population in Scotland. These findings are important to other countries, with injecting-related HCV epidemics, needing to scale-up testing/case-finding initiatives.

Parenteral ganciclovir treatment of acute CMV infection in the immunocompetent host

SummaryThe treatment with ganciclovir of two non-compromised patients who required hospitalisation with acute cytomegalovirus (CMV) infection is described. Ganciclovir has rarely been used in such circumstances but, in four previously reported patients and in the patients described here, a rapid response to therapy was seen. In contrast to previous reports, relatively short courses of treatment (3–5 days) were given to our patients. The drug was well tolerated in each case and may have a role to play in the treatment of severe acute CMV infection in the normal host.

Trends in the incidence of HIV in Scotland, 1988–2009

Objectives To estimate temporal trends in HIV incidence and prevalence in Scotland, according to three main risk groups for infection: men who have sex with men (MSM), injecting drug users (IDUs) and heterosexuals. Methods The authors extracted data for all single- and multiple-tested individuals from the national HIV test database covering the period 1980–2009 and calculated the incidence of HIV infection in each risk group and estimated RRs by fitting Poisson regression models. Results 620 of 59 807 individuals tested positive following an initial negative HIV test, generating an overall incidence rate of 3.7/1000 person-years (95% CI 3.4 to 4.0); 60%, 20% and 37% of the 620 were associated with the risk behaviour categories MSM, IDU and heterosexual, respectively. The incidence rate among MSM in Scotland remained relatively stable between the periods <1995 and 2005–2009 (overall: 15.3/1000 person-years, 95% CI 13.8 to 17.0), whereas the incidence among IDUs decreased between the periods <1995 and 2005–2009, from 5.1/1000 to 1.7/1000 person-years, and also decreased among heterosexuals, from 2.9/1000 to 1.4/1000 person-years. Conclusions The reduction in the incidence rate among IDUs suggests that harm reduction measures initiated from the late 1980s were effective in reducing HIV transmission in this risk group; however, the absence of a reduction in HIV incidence rates among MSM is disappointing and highlights the need for renewed efforts in the prevention of HIV in this major risk group.

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.

Severe Pneumonia After Cardiac Surgery as a Result of Infection With Parainfluenza Virus Type 4

UMAN PARAINFLUENZA VIRUS type 4 (HPIV4) is generally associated with mild respiratory disease. A case is presented in which the immunologic effects of cardiopulmonary bypass (CPB) and an undiagnosed community-acquired infection with HPIV4 conspired to cause fulminant respiratory and renal failure in a patient undergoing routine surgery. The benign reputation of HPIV4 may be related to the fact that the polymerase chain reaction (PCR) for the identification of HPIV4 is not widely available in routine diagnostic virology laboratories. HPIV4 is probably underdiagnosed and may be associated with severe illness. CASE REPORT

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.