Epidemiology of SARS-CoV-2 during the first three waves in Scotland: a national record linkage study.

BACKGROUND: The early COVID-19 pandemic in Scotland-defined as the era before widespread access to vaccination and monoclonal antibody treatment-can be characterised into three distinct waves: March-July 2020, July 2020-April 2021 and May-August 2021. Each wave was met with various societal restrictions in an effort to reduce disease transmission and associated morbidity and mortality. Understanding the epidemiology of infections during these waves can provide valuable insights into future pandemic planning. METHODS: Scottish RT-PCR testing data reported up until 8 August 2021, the day prior to most restrictions being lifted in Scotland, were included. Demographic characteristics including age, sex and social deprivation associated with transmission, morbidity and mortality were compared across waves. A case-control analysis for each wave was then modelled to further compare risk factors associated with death over time. RESULTS: Of the 349 904 reported cases, there were 18 099, 197 251 and 134 554 in waves 1, 2 and 3, respectively. Hospitalisations, intensive care unit admissions and deaths appeared highest in wave 2, though risk factors associated with COVID-19 death remained similar across the waves. Higher deprivation and certain comorbidities were associated with higher deaths in all waves. CONCLUSIONS: Despite the higher number of cases reported in waves 2 and 3, case fatality rates were lower: likely a combination of improved detection of infections in younger age groups, introduction of social measures and vaccination. Higher social deprivation and comorbidities resulted in higher deaths for all waves.

Population-level effectiveness of a national HIV preexposure prophylaxis programme in MSM.

OBJECTIVE: The aim of this study was to evaluate Scotland's national HIV preexposure prophylaxis (PrEP) programme in relation to PrEP uptake and associated population-level impact on HIV incidence among MSM. DESIGN: A retrospective cohort study within real-world implementation. METHODS: Comparison of HIV diagnoses from national surveillance data and HIV incidence within a retrospective cohort of HIV-negative MSM attending sexual health clinics from the National Sexual Health information system between the 2-year periods pre(July 2015-June 2017) and post(July 2017-June 2019) introduction of PrEP. RESULTS: Of 16 723 MSM attending sexual health services in the PrEP period, 3256 (19.5%) were prescribed PrEP. Between pre-PrEP and PrEP periods, new HIV diagnoses among MSM declined from 229 to 184, respectively [relative risk reduction (RRR): 19.7%, 95% confidence interval (95% CI) 2.5-33.8]; diagnosed recently acquired infections declined from an estimated 73 to 47, respectively (35.6%, 95% CI 7.1-55.4). Among MSM attending sexual health clinics, HIV incidence per 1000 person-years declined from 5.13 (95% CI 3.90-6.64) pre-PrEP to 3.25 (95% CI 2.30-4.47) in the PrEP period (adjusted IRR 0.57, 95% CI 0.37-0.87). Compared with the pre-PrEP period, incidence of HIV was lower in the PrEP period for those prescribed PrEP (aIRR 0.25, 95% CI 0.09-0.70) and for those not prescribed PrEP (aIRR 0.68, 95% CI 0.43-1.05). CONCLUSION: We demonstrate national population-level impact of PrEP for the first time in a real-world setting. HIV incidence reduced in MSM who had been prescribed PrEP and, to a lesser extent, in those who had not. Promotion of the benefits of PrEP needs to extend to MSM who do not access sexual health clinics.

Investigating the decline in Lymphogranuloma venereum diagnoses in men who have sex with men in the United Kingdom since 2016: an analysis of surveillance data.

Background Following an upward trajectory in Lymphogranuloma venereum (LGV) diagnoses in the UK from 2004 to 2016, with annual diagnoses increasing from 28 to 904, diagnoses fell to 641 in 2017; this was inconsistent with the upward trend in other bacterial sexually transmissible infections (STIs) between 2016 and 2017. An analysis of surveillance data from multiple sources to investigate the possible factors contributing to this decline in LGV was performed. METHODS: LGV tests and diagnoses in the UK from 2004 to 2018 were captured through laboratory data from the LGV Reference Laboratories and laboratories conducting in-house LGV testing. These data and clinical diagnoses data from England were analysed alongside the national management guidelines issued over the course of the epidemic. RESULTS: LGV diagnoses increased between 2004 and 2015 and then decreased between 2016 and 2018. LGV testing increased from 2010 to 2018 (2690-10850). Test positivity halved between 2015 (14.8%, 929-6272) and 2018 (7.3%, 791-10850). Peaks in LGV testing and diagnoses appeared to coincide with the publication of national LGV management guidelines and changes to clinical practice. The proportion of LGV diagnoses among HIV-positive men who have sex with men (MSM) fell between 2013 and 2018 (74-48%). CONCLUSIONS: The fall in diagnoses and positivity were likely due to increasing earlier clinical diagnosis and treatment. Changes to the national management guidelines, the clinical policy and practice of some larger clinics and potentially changes to the guidelines for the treatment of chlamydia broadened the scope of testing and increased testing in asymptomatic patients which, in combination, likely had a positive effect on the control of LGV infection.

A brief recent history of the epidemiology of congenital syphilis in the United Kingdom.

Within a century, congenital syphilis has been reduced from a major cause of morbidity and mortality to a condition rarely seen in the UK. Here, newly-derived literature and information searches were used to create a contemporary overview of the epidemic, including its epidemiology. Although constrained by high-quality healthcare services and with an incidence below the World Health Organization elimination threshold, congenital syphilis still has the potential to cause major consequences for the health and life chances of affected infants. If the complex challenges presented by this preventable disease are to be resolved, intervention strategies need to be optimised, rigorously assessed and extended across Europe.

100 years of STIs in the UK: a review of national surveillance data.

OBJECTIVES: The 1916 Royal Commission on Venereal Diseases was established in response to epidemics of syphilis and gonorrhoea in the UK. In the 100 years since the Venereal Diseases Act (1917), the UK has experienced substantial scientific, economic and demographic changes. We describe historical and recent trends in STIs in the UK. METHODS: We analysed surveillance data derived from STI clinics' statistical returns from 1917 to 2016. RESULTS: Since 1918, gonorrhoea and syphilis diagnoses have fluctuated, reflecting social, economic and technological trends. Following spikes after World Wars I and II, rates declined before re-emerging during the 1960s. At that time, syphilis was more common in men, suggestive of transmission within the men who have sex with men (MSM) population. Behaviour change following the emergence of HIV/AIDS in the 1980s is thought to have facilitated a precipitous decline in diagnoses of both STIs in the mid-1980s. Since the early 2000s, gonorrhoea and syphilis have re-emerged as major public health concerns due to increased transmission among MSM and the spread of antimicrobial-resistant gonorrhoea. Chlamydia and genital warts are now the most commonly diagnosed STIs in the UK and have been the focus of public health interventions, including the national human papillomavirus vaccination programme, which has led to substantial declines in genital warts in young people, and the National Chlamydia Screening Programme in England. Since the 1980s, MSM, black ethnic minorities and young people have experienced the highest STI rates. CONCLUSION: Although diagnoses have fluctuated over the last century, STIs continue to be an important public health concern, often affecting more marginalised groups in society. Prevention must remain a public health priority and, as we enter a new era of sexual healthcare provision including online services, priority must be placed on maintaining prompt access for those at greatest risk of STIs.

Association between universal hepatitis B prison vaccination, vaccine uptake and hepatitis B infection among people who inject drugs.

BACKGROUND AND AIMS: In Scotland, hepatitis B virus (HBV) vaccination for all prisoners was introduced in 1999; here, we examine the impact of this programme among people who inject drugs (PWID) in the community. This study aimed to compare rates of HBV vaccine uptake before and after implementation of the prison programme and to estimate the determinants of vaccine uptake, the levels of ever/current HBV infection and the associations between vaccine uptake and ever/current HBV infection. DESIGN: Data collected via serial cross-sectional surveys were used to compare the proportion who reported being vaccinated over time. For the 2013-14 survey, rates of ever/current HBV infection were calculated and the associations between vaccine uptake and ever/current HBV infection were examined using logistic regression. SETTING: Services providing injecting equipment and drug treatment and street sites in Glasgow (1993-2002) and throughout Scotland (2008-14). PARTICIPANTS: More than 10 000 PWID in total were recruited in the surveys. MEASUREMENTS: Participants completed a questionnaire (all years) to ascertain self-reported vaccine uptake and provided a blood spot (in 2013-14), tested for HBV core antibodies (anti-HBc) and surface antigen (HBsAg). FINDINGS: Among recent-onset PWID in Glasgow, vaccine uptake increased from 16% in 1993 to 59% in 2008-14 (P < 0.001). Among all PWID in Scotland, uptake increased further from 71% in 2008-09 to 77% in 2013-14 (P < 0.001) and was associated with incarceration [adjusted odds ratio (aOR) = 2.91, 95% confidence interval (CI) = 2.23-3.79]. The prevalence of anti-HBc and HBsAg in Scotland was 2.6 and 0.3%, respectively, among PWID who had commenced injecting in the decade since the programme's introduction. Vaccination was associated with reduced odds of ever (aOR = 0.60, CI = 0.37-0.97) and current (aOR = 0.40, CI = 0.16-0.97) HBV infection. CONCLUSIONS: In Scotland, uptake of hepatitis B virus (HBV) vaccination among people who inject drugs (PWID) in the community has increased since the 1999 introduction of universal prison vaccination, and current levels of HBV infection among PWID are low compared with other European countries.

Development of an avidity assay for detection of recent HIV infections.

HIV avidity can measure the incidence of recent infections within the population. The aim of this study was to evaluate an HIV avidity assay, initially from a clinically defined group of patients and then apply the assay to a prospective study to determine the false recency rate and mean duration of recency for the assay. The assay is a commercial ELISA modified with 7 M urea. The validation of the assay used plasma from patients split into Group 1 (recently infected N=25) and group 2 (established infection N=301). The prospective study tested 178 newly diagnosed HIV patients for avidity. A total of 326 retrospective samples of known HIV status were collected and tested. The initial evaluation gave a sensitivity 100% (CI 86.16-100%) and specificity of 98.65% (95% CI 97.05-99.78%). The prospective study incorporating 178 newly diagnosed patients found 22 patients with low avidity. Follow-up samples obtained from low avidity patients determined the estimated mean duration of recency to be between 3 and 4 months with a false recency rate of 0.89% (CI: 0.24-2.3%). The assay described here compares well in sensitivity, specificity and false recency rate with that of other published avidity assays.

Impact and cost-effectiveness of chlamydia testing in Scotland: a mathematical modelling study.

BACKGROUND: Chlamydia is the most common sexually transmitted bacterial infection in Scotland, and is associated with potentially serious reproductive outcomes, including pelvic inflammatory disease (PID) and tubal factor infertility (TFI) in women. Chlamydia testing in Scotland is currently targeted towards symptomatic individuals, individuals at high risk of existing undetected infection, and young people. The cost-effectiveness of testing and treatment to prevent PID and TFI in Scotland is uncertain. METHODS: A compartmental deterministic dynamic model of chlamydia infection in 15-24 year olds in Scotland was developed. The model was used to estimate the impact of a change in testing strategy from baseline (16.8% overall testing coverage; 0.4 partners notified and tested/treated per treated positive index) on PID and TFI cases. Cost-effectiveness calculations informed by best-available estimates of the quality-adjusted life years (QALYs) lost due to PID and TFI were also performed. RESULTS: Increasing overall testing coverage by 50% from baseline to 25.2% is estimated to result in 21% fewer cases in young women each year (PID: 703 fewer; TFI: 88 fewer). A 50% decrease to 8.4% would result in 20% more PID (669 additional) and TFI (84 additional) cases occurring annually. The cost per QALY gained of current testing activities compared to no testing is £40,034, which is above the £20,000-£30,000 cost-effectiveness threshold. However, calculations are hampered by lack of reliable data. Any increase in partner notification from baseline would be cost-effective (incremental cost per QALY gained for a partner notification efficacy of 1 compared to baseline: £5,119), and would increase the cost-effectiveness of current testing strategy compared to no testing, with threshold cost-effectiveness reached at a partner notification efficacy of 1.5. However, there is uncertainty in the extent to which partner notification is currently done, and hence the amount by which it could potentially be increased. CONCLUSIONS: Current chlamydia testing strategy in Scotland is not cost-effective under the conservative model assumptions applied. However, with better data enabling some of these assumptions to be relaxed, current coverage could be cost-effective. Meanwhile, increasing partner notification efficacy on its own would be a cost-effective way of preventing PID and TFI from current strategy.

Results from a national treatment database - does it matter which ART combination is prescribed in the real world?

INTRODUCTION: Clinical trials frequently show differences in viral load (VL) response between antiretroviral therapy (ART) regimes. Patterns of prescribing vary from country to country (Mocroft et al. Infection 2014 Jun 6 [epub ahead of print]), and are likely to vary between individual clinics. Scotland has a national database that records VL results and specific ART regimes for every patient under care, thus allowing different prescribing patterns between clinical centres to be monitored. Does this reveal any difference in achievement of undetectable VL? MATERIALS AND METHODS: We interrogated the database held by Health Protection Scotland (HPS) that contains a record of every VL result matched against prescribed ART. RESULTS were censored at the end of December 2013 and are based on the latest attendance of patients who have been under monitoring for at least six months. For simplicity, we have broken the results into class of drug rather than individual drugs for example, nucleoside reverse transcriptase inhibitor (NRTI) rather than lamivudine, abacavir etc. The data were analyzed using univariate Poisson regression. RESULTS: The anonymized records of 3302 individual patients who attended in 11 separate regions were scrutinized. Sixty-eight different combinations of antiretroviral regimes were identified. The prescribing patterns for the five most frequently prescribed regimes in the four largest clinics are shown in Table 1, along with the overall percentage of patients with undetectable VL. A higher proportion of patients in Scotland who are prescribed regimes of NRTI×2 or NRTI/NtRTI plus PI have detectable VL but this is not statistically significant. Although the percentage of patients with VL<50 varies between regions 1 and 4 versus regions 2 and 3, this is also not statistically significant. CONCLUSIONS: Overall, a high proportion of Scottish patients on ART have undetectable VL. Patterns of ART prescribing in Scotland do vary by region but there are no significant differences in outcome with regard to undetectable VL. There is a non-significant trend which may be accounted for by differing levels of PI prescribing.

HIV prevalence and undiagnosed infection among a community sample of gay and bisexual men in Scotland, 2005-2011: implications for HIV testing policy and prevention.

OBJECTIVE: To examine HIV prevalence, HIV testing behaviour, undiagnosed infection and risk factors for HIV positivity among a community sample of gay men in Scotland. METHODS: Cross-sectional survey of gay and bisexual men attending commercial gay venues in Glasgow and Edinburgh, Scotland with voluntary anonymous HIV testing of oral fluid samples in 2011. A response rate of 65.2% was achieved (1515 participants). RESULTS: HIV prevalence (4.8%, 95% confidence interval, CI 3.8% to 6.2%) remained stable compared to previous survey years (2005 and 2008) and the proportion of undiagnosed infection among HIV-positive men (25.4%) remained similar to that recorded in 2008. Half of the participants who provided an oral fluid sample stated that they had had an HIV test in the previous 12 months; this proportion is significantly higher when compared to previous study years (50.7% versus 33.8% in 2005, p<0.001). Older age (>25 years) was associated with HIV positivity (1.8% in those <25 versus 6.4% in older ages group) as was a sexually transmitted infection (STI) diagnosis within the previous 12 months (adjusted odds ratio 2.13, 95% CI 1.09-4.14). There was no significant association between age and having an STI or age and any of the sexual behaviours recorded. CONCLUSION: HIV transmission continues to occur among gay and bisexual men in Scotland. Despite evidence of recent testing within the previous six months, suggesting a willingness to test, the current opt-out policy may have reached its limit with regards to maximising HIV test uptake. Novel strategies are required to improve regular testing opportunities and more frequent testing as there are implications for the use of other biomedical HIV interventions.

Estimation of the risk of tubal factor infertility associated with genital chlamydial infection in women: a statistical modelling study.

OBJECTIVES: Using a statistical modelling approach, our study aim is to determine reliable age-related estimates of the risk of all-cause tubal factor infertility (TFI) following past or current chlamydial infection in women in Scotland. METHOD: Using data from several sources, a Markov-Chain Monte Carlo model was used to estimate the age-related risk of TFI given genital chlamydia infection at any time. The analysis is based on the probability of a woman ever having chlamydial infection, ever having TFI and ever having a previous chlamydial infection given a diagnosis of TFI. The model was programmed and evaluated using WinBugs14. RESULTS: By the age 44 years, the overall risk of a woman having at least a single chlamydial infection is estimated at 42.9% (95% credible interval 30.0, 59.0%). The risk of a woman having TFI increased from 0.5% in those aged 16-19 years to 0.8% in those aged 40-44. The overall estimated probability of TFI, based on lifetime infertility, given a past or current chlamydial infection, is relatively consistent across all five age groups from 16-44 years, being 0.9% among those aged 25-29 and 1.4% in those aged 35-39; The estimates were found to be sensitive to the definition of infertility, with the estimate increasing from 1.3% in the youngest age group to 2.8% and 4.5% for 24-month primary infertility and primary or secondary infertility, respectively. CONCLUSIONS: At the population level, the likelihood of all-cause TFI in those with past or current chlamydial infection is low. These findings have relevance both at the policy level, in the development of control programmes, and also at an individual level, particularly for clinicians supporting women undergoing testing or with a positive diagnosis.

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.

Virological surveillance of influenza-like illness in the community using PCR and serology.

BACKGROUND: Surveillance of winter respiratory viral illness has been carried out for nearly 30 years using a clinical diagnosis by general practitioners as part of the Scottish Sentinel General Practice (SSGP) network. Contemparaneous laboratory diagnosis has not been available previously. OBJECTIVES: To assess the proportion of influenza-like illness (ILI) attributable to influenza, respiratory syncytial virus (RSV) and picornavirus infection during the winter season. To compare the influenza PCR data with serology of paired blood samples. STUDY DESIGN: Combined nose and throat swabs, from patients with ILI attending 15 general practices across Scotland, were submitted to the laboratory in virus PCR sample solution (VPSS). The extracted nucleic acid was tested using a multiplex reverse-transcription polymerase chain reaction (RT-PCR) assay. Serological analysis was performed on paired serum samples using complement fixation assays. The rate of influenza virus positivity was compared with reports of ILI obtained from the SSGP network. RESULTS: Of 240 samples received at the laboratory, 132 (55%) were PCR positive for influenza A virus. There were nine (3.8%) picornavirus and three (1.2%) RSV PCR positives, two (0.8%) were dual influenza A/picornavirus infections. Ninety four (39.2%) were negative for all viruses tested. Results on paired sera from 89 patients showed a rising titre to influenza A in 48 of the 57 PCR positive samples (84.2%). One PCR negative patient displayed a significant rising titre to influenza A. Virological data paralleled the SSGP data but was available at least a week earlier. CONCLUSIONS: Influenza A infection was detected in the majority of patients with ILI; picornavirus infection was also shown to be an important cause of illness. PCR is a rapid and sensitive method for respiratory virus surveillance. Serology is slow, insensitive and difficult to interpret at low titres.