Invasive cervical cancer incidence following bivalent human papillomavirus vaccination: a population-based observational study of age at immunization, dose, and deprivation.

BACKGROUND: High-risk human papillomavirus causes cervical cancer. Vaccines have been developed that significantly reduce the incidence of preinvasive and invasive disease. This population-based observational study used linked screening, immunization, and cancer registry data from Scotland to assess the influence of age, number of doses, and deprivation on the incidence of invasive disease following administration of the bivalent vaccine. METHODS: Data for women born between January 1, 1988, and June 5, 1996, were extracted from the Scottish cervical cancer screening system in July 2020 and linked to cancer registry, immunization, and deprivation data. Incidence of invasive cervical cancer per 100 000 person-years and vaccine effectiveness were correlated with vaccination status, age at vaccination, and deprivation; Kaplan Meier curves were calculated. RESULTS: No cases of invasive cancer were recorded in women immunized at 12 or 13 years of age irrespective of the number of doses. Women vaccinated at 14 to 22 years of age and given 3 doses of the bivalent vaccine showed a significant reduction in incidence compared with all unvaccinated women (3.2/100 000 [95% confidence interval (CI) = 2.1 to 4.6] vs 8.4 [95% CI = 7.2 to 9.6]). Unadjusted incidence was significantly higher in women from most deprived (Scottish Index of Multiple Deprivation 1) than least deprived (Scottish Index of Multiple Deprivation 5) areas (10.1/100 000 [95% CI = 7.8 to 12.8] vs 3.9 [95% CI = 2.6 to 5.7]). Women from the most deprived areas showed a significant reduction in incidence following 3 doses of vaccine (13.1/100 000 [95% CI = 9.95 to 16.9] vs 2.29 [95% CI = 0.62 to 5.86]). CONCLUSION: Our findings confirm that the bivalent vaccine prevents the development of invasive cervical cancer and that even 1 or 2 doses 1 month apart confer benefit if given at 12-13 years of age. At older ages, 3 doses are required for statistically significant vaccine effectiveness. Women from more deprived areas benefit more from vaccination than those from less deprived areas.

The changing nature of HPV associated with high grade cervical lesions in vaccinated populations, a retrospective study of over 1700 cases in Scotland.

BACKGROUND: Understanding the pattern and dominance of HPV types in high grade cervical disease within increasingly vaccinated populations will help inform the development of appropriate screening and management protocols. METHODS: Over 1700 cases of cervical intraepithelial neoplasia (CIN) diagnosed between 2011 and 2017 in women younger than 25 were genotyped for HPV. Logistic regression was used to assess the association between HPV 16/18 positivity with biopsy-collection year, birth year, deprivation and vaccination status. Regression analysis was repeated for cross-protective types (31, 33 and 45). Type specific detail of non-vaccine types by vaccination status was presented descriptively. RESULTS: Detection of HPV 16/18 or 16/18/31/33 and 45 was lower in CIN2 associated with full vaccination vs no vaccination (OR 0.3; 95% CI 0.2-0.5 & 0.4; 95% CI 0.3-0.6 respectively) Similar observations were made for CIN3. The relative contribution of non-established high-risk types including those considered low risk was greater among vaccinated women with CIN2+ vs unvaccinated women with CIN2+. CONCLUSIONS: The change in HPV distribution in CIN2+ in vaccinated populations is a further marker of vaccine impact. Additionally, the progression rate of CIN2+ in vaccinated populations may be lower given the shift in type distribution. The definition of high grade disease in vaccinated populations may warrant reassessment.

Adeno-associated virus 2 infection in children with non-A-E hepatitis.

An outbreak of acute hepatitis of unknown aetiology in children was reported in Scotland1 in April 2022 and has now been identified in 35 countries2. Several recent studies have suggested an association with human adenovirus with this outbreak, a virus not commonly associated with hepatitis. Here we report a detailed case-control investigation and find an association between adeno-associated virus 2 (AAV2) infection and host genetics in disease susceptibility. Using next-generation sequencing, PCR with reverse transcription, serology and in situ hybridization, we detected recent infection with AAV2 in plasma and liver samples in 26 out of 32 (81%) cases of hepatitis compared with 5 out of 74 (7%) of samples from unaffected individuals. Furthermore, AAV2 was detected within ballooned hepatocytes alongside a prominent T cell infiltrate in liver biopsy samples. In keeping with a CD4+ T-cell-mediated immune pathology, the human leukocyte antigen (HLA) class II HLA-DRB1*04:01 allele was identified in 25 out of 27 cases (93%) compared with a background frequency of 10 out of 64 (16%; P = 5.49 × 10-12). In summary, we report an outbreak of acute paediatric hepatitis associated with AAV2 infection (most likely acquired as a co-infection with human adenovirus that is usually required as a 'helper virus' to support AAV2 replication) and disease susceptibility related to HLA class II status.

Investigation into cases of hepatitis of unknown aetiology among young children, Scotland, 1 January 2022 to 12 April 2022.

On 31 March 2022, Public Health Scotland was alerted to five children aged 3-5 years admitted to hospital with severe hepatitis of unknown aetiology. Retrospective investigation identified eight additional cases aged 10 years and younger since 1 January 2022. Two pairs of cases have epidemiological links. Common viral hepatitis causes were excluded in those with available results. Five children were adenovirus PCR-positive. Other childhood viruses, including SARS-CoV-2, have been isolated. Investigations are ongoing, with new cases still presenting.

The experiences of people who inject drugs of skin and soft tissue infections and harm reduction: A qualitative study.

BACKGROUND: Bacterial skin and soft tissue infections (SSTI) among people who inject drugs (PWID) are considered a public health concern. There is a lack of qualitative research examining the lived experience of PWID who have had SSTI. This paper explores PWID views and experiences of their SSTI, their perceptions on the causes of their SSTI and their harm reduction (HR) behaviours. The implications for HR service delivery and practice will be discussed. METHODS: Between October 2015-January 2016, 22 in-depth interviews were conducted with PWID who had experienced a SSTI within the past year. Interviewees were recruited from an injecting equipment provision service and a drug treatment service in Glasgow and Edinburgh respectively. The interview transcripts were transcribed verbatim and underwent thematic analysis. RESULTS: We found that the experience of SSTI can cause strong negative feelings, including panic and stigma and that there was limited knowledge of SSTI prior to first hand experience. The awareness of the unacceptable social and physical consequences of SSTI fostered a sense of personal responsibility and agency which led to the introduction or improved HR uptake. However, when PWID were struggling to inject or when their physical and political environments were compromised there was an increased risk for SSTI and reduced effectiveness of HR. CONCLUSION: Compared to HCV and HIV, SSTI as an injecting related harm has received less policy attention. Policy makers need to address SSTI HR within enabling environments, such as 'safer environment interventions'. It is recommended that peer based support, improved NSP provision and medically supervised injecting facilities are needed to deliver SSTI HR.

A pragmatic harm reduction approach to manage a large outbreak of wound botulism in people who inject drugs, Scotland 2015.

BACKGROUND: People who inject drugs (PWID) are at an increased risk of wound botulism, a potentially fatal acute paralytic illness. During the first 6 months of 2015, a large outbreak of wound botulism was confirmed among PWID in Scotland, which resulted in the largest outbreak in Europe to date. METHODS: A multidisciplinary Incident Management Team (IMT) was convened to conduct an outbreak investigation, which consisted of enhanced surveillance of cases in order to characterise risk factors and identify potential sources of infection. RESULTS: Between the 24th of December 2014 and the 30th of May 2015, a total of 40 cases were reported across six regions in Scotland. The majority of the cases were male, over 30 and residents in Glasgow. All epidemiological evidence suggested a contaminated batch of heroin or cutting agent as the source of the outbreak. There are significant challenges associated with managing an outbreak among PWID, given their vulnerability and complex addiction needs. Thus, a pragmatic harm reduction approach was adopted which focused on reducing the risk of infection for those who continued to inject and limited consequences for those who got infected. CONCLUSIONS: The management of this outbreak highlighted the importance and need for pragmatic harm reduction interventions which support the addiction needs of PWID during an outbreak of spore-forming bacteria. Given the scale of this outbreak, the experimental learning gained during this and similar outbreaks involving spore-forming bacteria in the UK was collated into national guidance to improve the management and investigation of future outbreaks among PWID.

Spore forming bacteria infections and people who inject drugs: Implications for harm reduction.

BACKGROUND: There is no research on public health interventions that alert people who inject drugs (PWID) to clusters/outbreaks of severe bacterial infections. In Scotland, during the botulism cluster/outbreak of Dec 2014-July 2015 harm reduction (HR) messages detailed on a postcard (Botulism Postcard) were distributed to PWID between Feb-April 2015. We examined the impact of the Botulism Postcard on cluster/outbreak awareness, healthcare seeking and HR behaviours among PWID; and their views on such clusters/outbreaks. METHODS: The Botulism Postcard questionnaire survey was undertaken with 288 PWID recruited in Greater Glasgow and Clyde between May-August 2015. Multivariate logistic regression was undertaken. Between Oct 2015-January 2016 22 in-depth interviews were conducted with PWID in Glasgow and Edinburgh, these underwent thematic analysis. RESULTS: 38% (108/284) had never seen the postcard, 14% (40/284) had only seen it, 34% (98/284) read but not discussed it and 13% (38/284) had discussed it with service staff. Cluster/outbreak awareness was higher among those who had read (adjusted odds ratio (aOR) = 5.374, CI 2.394-11.349, p < 0.001) or discussed the postcard (aOR = 25.114, CI 3.188-190.550, p < 0.001); and symptom awareness was higher among those who had read (aOR = 2.664, CI 1.322-4.890, p < 0.001) or discussed the postcard (aOR = 6.707, CI 2.744 16.252, p < 0.001) than among those who had never seen it. The odds of introducing HR was higher among those who had discussed the postcard (AOR = 3.304 CI 1.425 7.660, p < 0.01) than those who had only read it. PWID learnt about clusters/outbreaks from several sources and despite concerns they continued to inject during such events. CONCLUSION: More widespread exposure to the Botulism Postcard during the outbreak/cluster was needed. The Botulism Postcard distributed to PWID may raise awareness of such events, the symptoms, and may encourage HR particularly when used as a tool by frontline staff to initiate discussion. Acknowledging that people continue to inject during clusters/outbreaks of such infections necessitates a pragmatic HR approach.

Association between harm reduction intervention uptake and skin and soft tissue infections among people who inject drugs.

BACKGROUND: Bacterial skin and soft tissue infections (SSTIs) are a health issue for people who inject drugs (PWID). There is a lack of evidence on the associations between harm reduction (HR) uptake and SSTIs. This paper examines the associations between the uptake of injecting equipment (IE) and opiate substitution treatment (OST) on SSTIs among PWID, and the injecting behaviours associated with having had an SSTI. This is the first large-scale, national study to examine the association between IE uptake and SSTIs. METHODS: A cross-sectional, voluntary and anonymous survey was undertaken with PWID recruited from pharmacies/agencies providing IE across mainland Scotland during 2013-2014. Participants were asked: if they had an SSTI within the past year; about their uptake of HR within the past 6 months (including needle/syringes (N/S), paraphernalia and OST); and about their frequency of injecting, sharing of IE and re-use of own N/S. Data from 1876 PWID who had reported injecting within the past 6 months were analysed. FINDINGS: In multivariate logistic regression, those with high combined IE-OST uptake (adjusted odds ratio [AOR] 0.614, 95% CI 0.458-0.823, p=0.001) and medium combined IE-OST uptake (AOR 0.725, 95% CI 0.546-0.962, p=0.026) had lower odds of having had an SSTI compared to those with low combined IE-OST uptake. CONCLUSIONS: IE and OST uptake may reduce the level of SSTIs among PWID, suggesting increasing combined uptake may be beneficial. Nevertheless, a sizeable proportion of PWID with high HR uptake experienced SSTIs, suggesting the importance of other interventions.

Polyelectrolyte Layer-by-Layer Assembly on Organic Electrochemical Transistors.

Oppositely charged polyelectrolyte multilayers (PEMs) were built up in a layer-by-layer (LbL) assembly on top of the conducting polymer channel of an organic electrochemical transistor (OECT), aiming to combine the advantages of well-established PEMs with a high performance electronic transducer. The multilayered film is a model system to investigate the impact of biofunctionalization on the operation of OECTs comprising a poly(3,4-ethylenedioxythiophene) polystyrenesulfonate (PEDOT:PSS) film as the electrically active layer. Understanding the mechanism of ion injection into the channel that is in direct contact with charged polymer films provides useful insights for novel biosensing applications such as nucleic acid sensing. Moreover, LbL is demonstrated to be a versatile electrode modification tool enabling tailored surface features in terms of thickness, softness, roughness, and charge. LbL assemblies built up on top of conducting polymers will aid the design of new bioelectronic platforms for drug delivery, tissue engineering, and medical diagnostics.

The seroprevalence of hepatitis C virus infection among children and their mothers attending for dental care in Glasgow, Scotland, United Kingdom.

This paper describes a voluntary anonymous survey to investigate the seroprevalence of Hepatitis C (HCV) in children in Glasgow, UK attending a Dental Hospital and the proportion of HCV positive mothers who have a child who is HCV seropositive. The study was undertaken among children and accompanying parents and household contacts attending a general anaesthetic assessment clinic at Glasgow Dental Hospital and School. Children were asked to provide an oral fluid specimen for HCV testing. Accompanying adults were asked to provide demographic data on the child and information on familial risk factors for HCV infection using a standardised questionnaire. Birth mothers were also asked to provide an oral fluid specimen. Specimens and questionnaires were linked by a unique anonymous study number. Between June 2009 and December 2011, samples were collected from 2141 children and 1698 mothers. None of the samples from the children were HCV seropositive but 16 (0.9%, 95% CI 0.6-1.5%) of the specimens from mothers were HCV antibody positive. In summary, the prevalence of HCV seropositivity in the birth mothers of the children was similar to that estimated in the general population served by the hospital and showed no evidence of mother-to-child transmission of HCV.

Interventions to prevent HIV and Hepatitis C in people who inject drugs: a review of reviews to assess evidence of effectiveness.

BACKGROUND: Injecting drug use is a major risk factor for the acquisition and transmission of HIV and Hepatitis C virus (HCV). Prevention of these infections among people who inject drugs (PWID) is critical to reduce ongoing transmission, morbidity and mortality. METHODS: A review of reviews was undertaken involving systematic literature searches of Medline, Embase, CINAHL, PsychINFO, IBSS and the Cochrane Library (2000-2011) to identify English language reviews regarding the effectiveness of harm reduction interventions in relation to HIV transmission, HCV transmission and injecting risk behaviour (IRB). Interventions included needle and syringe programmes (NSP); the provision of injection paraphernalia; opiate substitution treatment (OST); information, education and counselling (IEC); and supervised injecting facilities (SIFs). Reviews were classified into 'core' or 'supplementary' using critical appraisal criteria, and the strength of review-level evidence was assessed. RESULTS: Twelve core and thirteen supplementary reviews were included. From these reviews we identified: (i) for NSP: tentative review-level evidence to support effectiveness in reducing HIV transmission, insufficient review-level evidence relating to HCV transmission, but sufficient review-level evidence in relation to IRB; (ii) for OST: sufficient review-level evidence of effectiveness in relation to HIV transmission and IRB, but tentative review-level evidence in relation to HCV transmission; (iii) for IEC, the provision of injection paraphernalia and SIFs: tentative review-level evidence of effectiveness in reducing IRB; and either insufficient or no review-level evidence for these interventions in relation to HIV or HCV transmission. CONCLUSION: Review-level evidence indicates that harm reduction interventions can reduce IRB, with evidence strongest for OST and NSP. However, there is comparatively little review-level evidence regarding the effectiveness of these interventions in preventing HCV transmission among PWID. Further studies are needed to assess the effectiveness and impact of scaling up comprehensive packages of harm reduction interventions to minimise HIV and HCV transmission among PWID.

Infections with spore-forming bacteria in persons who inject drugs, 2000-2009.

Since 2000 in the United Kingdom, infections caused by spore-forming bacteria have been associated with increasing illness and death among persons who inject drugs (PWID). To assess temporal and geographic trends in these illnesses (botulism, tetanus, Clostridium novyi infection, and anthrax), we compared rates across England and Scotland for 2000-2009. Overall, 295 infections were reported: 1.45 per 1,000 PWID in England and 4.01 per 1,000 PWID in Scotland. The higher rate in Scotland was mainly attributable to C. novyi infection and anthrax; rates of botulism and tetanus were comparable in both countries. The temporal and geographic clustering of cases of C. novyi and anthrax into outbreaks suggests possible contamination of specific heroin batches; in contrast, the more sporadic nature of tetanus and botulism cases suggests that these spores might more commonly exist in the drug supply or local environment although at varying levels. PWID should be advised about treatment programs, injecting hygiene, risks, and vaccinations.

Benchmarking self-reported practice regarding Scottish Executive guidance on hepatitis C-infected health care workers.

BACKGROUND: The 2002 Scottish Executive guidance 'hepatitis C-infected health care workers' advised NHS Scotland occupational health departments regarding screening health care workers (HCW) who perform or who may perform exposure-prone procedures (EPPs) for hepatitis C virus (HCV) infection. In 2004, 2 years following the launch of the guidance, there was anecdotal evidence of challenges to implementation and clinical and ethical concerns regarding the screening process. AIM: To benchmark the implementation of the Executive guidance on hepatitis C-infected HCW in NHS Scotland. METHODS: Lead occupational health practitioners in 15 Scottish NHS Boards completed a questionnaire and provided relevant local policies. RESULTS: All 15 NHS Boards responded: 87% (n = 13) had implemented the guidance with partial implementation in the remaining boards. While 87% required identified and validated samples (IVS), no consistent method was reported for how results from an IVS were recorded. There was also no consensus as to the duration a result was considered valid or consistency in charging for tests required by other employers. Across Scotland, some employee groups were being screened over and above those recommended within the guidance. Overall, there was agreement on the value of a standardized NHS hepatitis C status certificate and the importance of explicit screening criteria and identifying EPP workers. CONCLUSION: The survey confirms the challenges in implementing the guidance on managing HCV-infected HCW within NHS Scotland. These include lack of clarity regarding who, when and how frequently a HCW should be screened and how the results of such tests should be recorded.

Does the recent increase in HIV diagnoses among men who have sex with men in the UK reflect a rise in HIV incidence or increased uptake of HIV testing?

OBJECTIVES: To determine whether the increase in HIV diagnoses since 1997 among men who have sex with men (MSM) in the UK reflects a rise in HIV incidence or an increase in HIV testing. METHODS: Estimates of HIV incidence were derived using data from UK HIV surveillance systems (HIV diagnoses; CD4 surveillance; unlinked anonymous surveys) for 1997-2004. Data on HIV testing were provided by KC60 statutory returns, voluntary testing and unlinked anonymous surveys in sentinel genitourinary medicine (GUM) clinics. RESULTS: HIV diagnoses among MSM in the UK rose by 54% between 1997 and 2004 (from 1382 to 2124), with variation by age and geographical location. The number of HIV diagnoses among MSM <35 years of age in London showed no increase, but in all other groups it increased. Throughout the UK, uptake of HIV testing increased significantly among MSM attending GUM clinics between 1997 and 2004, including "at-risk" MSM (p<0.001). Direct incidence estimates (serological testing algorithm for recent HIV seroconversion assay) provided no evidence of a statistically significant increase or decrease in HIV incidence. Indirect estimates suggested that there may have been a rise in HIV incidence, but these estimates were influenced by the increased uptake of HIV testing. CONCLUSIONS: The number of HIV diagnoses increased among MSM in the UK between 1997 and 2004, except among younger MSM in London, in whom there was no change. The increase in HIV diagnoses among MSM in the UK since 1997 seems to reflect an increase in HIV testing rather than a rise in HIV incidence.

Anonymous pilot study of hepatitis C virus prevalence in liver transplant surgeons.

The risk of hepatitis C virus (HCV) transmission to surgeons is related to the HCV prevalence in the surgical patient population. As HCV-related cirrhosis is the commonest indication for liver transplantation in Europe and North America, liver transplant surgeons are at particular risk. The prevalence of HCV infection in liver transplant surgeons is unknown. The aim of this study was to estimate the prevalence of HCV infection in liver transplant surgeons attending the 9th Congress of the International Liver Transplantation Society using unlinked anonymous testing for HCV. Surgeons attending the conference were invited to complete an anonymised questionnaire regarding their surgical and transplant practice and provide an unlinked anonymised blood spot sample by finger prick. Samples were screened for antibodies to HCV (enzyme-linked immunosorbent assay III, Ortho Diagnostics, Raritan, NJ). Polymerase chain reaction testing for HCV RNA was performed on reactive samples.A total of 117 liver transplant surgeons (79 European, 16 North American, 10 Asian, 9 South American, 3 Australasian) provided a blood spot sample. Two (1.7%) surgeons had antibodies to HCV, 1 (0.8%) had detectable HCV RNA (genotype 1a). Assuming that both infections were acquired during surgery, the estimated maximum rate of HCV transmission is 1 per 743 to 1,045 years of surgical (0.96 to 1.35 HCV transmissions per 1,000 years of general surgical practice) and 449 to 683 years of liver transplant practice (1.46 to 2.23 HCV transmissions per 1,000 years of liver transplantation practice). In conclusion, risk of HCV transmission to liver transplant surgeons appears to be low despite the particular risks associated with frequently operating on HCV infected patients.

Investigating the source of hepatitis C virus infection among individuals whose route of infection is undefined: a study of ten cases.

Hepatitis C virus (HCV) transmission is predominantly parenteral via infected blood products or shared injecting equipment. Many infected individuals, however, deny these risk factors. This study set out to determine whether an in-depth interview would determine the likely source of infection for those whose route of infection was undefined. Between May 1999 and July 1999, risk factor information was sought, through in-depth interview, from 10 patients whose source of hepatitis C infection was undefined. The clinical notes of the patients were scrutinized to complement the information provided through the questionnaire. Despite undertaking an in-depth interview, it was not possible to establish the likely route of infection for 9 of the 10 individuals studied as they reported several risk events. There is little benefit to interviewing routinely those HCV-infected people who have no history of injecting drugs or having received a contaminated blood/blood product transfusion, to ascertain their likely source or time of infection; at best, such effort might only increase one's confidence that infection was acquired through means other than these 2 routes.

Prevalence of GBV-C infection among dental personnel.

Healthcare workers who carry out exposure-prone procedures are theoretically at increased risk of acquiring blood-borne virus infections. GB virus C (GBV-C) is a recently described blood-borne virus that is related distantly to hepatitis C virus. The occupational risk of GBV-C infection to healthcare workers is unknown. This study collected detailed occupational and personal risk data in parallel with a blood specimen, to establish the prevalence and determinants of GBV-C infection among dental healthcare workers. The presence of GBV-C antibodies was detected using commercially available ELISA; GBV-C RNA was detected by nested PCR using primers from the conserved 5' noncoding region. The overall prevalence of GBV-C antibodies among the study population was 11.1% (98/880, 95% confidence interval [CI], 9.1-13.4%) and 4.6% were positive for GBV-C RNA (46/879, 95% CI, 2.5-5.1%), resulting in a cumulative prevalence of 15.7%. These figures are similar to those described in other populations. There was no significant difference in lifetime exposure to GBV-C between dentists (17.7%) and dental nurses/hygienists (14.3%). Significantly more dental nurses/hygienists aged 16-30 years had been exposed to GBV-C compared to dentists of the same age (chi(2) = 13.75; P < 0.001). Conversely, significantly more dentists 46 years or older had evidence of exposure to GBV-C compared to dental nurses/hygienists (chi(2) = 6.79; P = 0.009). The high prevalence of GBV-C infection did not seem to be related to past parenteral exposure, and the data suggest that sexual transmission, rather than occupational transmission, was a more important route for GBV-C infection among this population.