Multi-omics microsampling for the profiling of lifestyle-associated changes in health.

Current healthcare practices are reactive and use limited physiological and clinical information, often collected months or years apart. Moreover, the discovery and profiling of blood biomarkers in clinical and research settings are constrained by geographical barriers, the cost and inconvenience of in-clinic venepuncture, low sampling frequency and the low depth of molecular measurements. Here we describe a strategy for the frequent capture and analysis of thousands of metabolites, lipids, cytokines and proteins in 10 µl of blood alongside physiological information from wearable sensors. We show the advantages of such frequent and dense multi-omics microsampling in two applications: the assessment of the reactions to a complex mixture of dietary interventions, to discover individualized inflammatory and metabolic responses; and deep individualized profiling, to reveal large-scale molecular fluctuations as well as thousands of molecular relationships associated with intra-day physiological variations (in heart rate, for example) and with the levels of clinical biomarkers (specifically, glucose and cortisol) and of physical activity. Combining wearables and multi-omics microsampling for frequent and scalable omics may facilitate dynamic health profiling and biomarker discovery.

Influence of SARS-CoV-2 surveillance outputs produced by the UK health security agency (UKHSA) outbreak surveillance team on decision-making by local stakeholders.

BACKGROUND: The UK Health Security Agency (UKHSA) COVID-19 Outbreak Surveillance Team (OST) was established in June 2020 to provide Local Authorities (LAs) in England with surveillance intelligence to aid their response to the SARS-CoV-2 epidemic. Reports were produced using standardised metrics in an automated format. Here we evaluate how the SARS-CoV-2 surveillance reports influenced decision making, how resources evolved and how they could be refined to meet the requirements of stakeholders in the future. METHODS: Public health professionals (n = 2,400) involved in the COVID-19 response from the 316 English LAs were invited to take part in an online survey. The questionnaire covered five themes: (i) report use; (ii) influence of surveillance outputs on local intervention strategies; (iii) timeliness; (iv) current and future data requirements; and (v) content development. RESULTS: Of the 366 respondents to the survey, most worked in public health, data science, epidemiology, or business intelligence. Over 70% of respondents used the LA Report and Regional Situational Awareness Report daily or weekly. The information had been used by 88% to inform decision making within their organisations and 68% considered that intervention strategies had been instituted as a result of these decisions. Examples of changes instigated included targeted communications, pharmaceutical and non-pharmaceutical interventions, and the timing of interventions. Most responders considered that the surveillance content had reacted well to evolving demands. The majority (89%) said that their information requirements would be met if the surveillance reports were incorporated into the COVID-19 Situational Awareness Explorer Portal. Additional information suggested by stakeholders included vaccination and hospitalisation data as well as information on underlying health conditions, infection during pregnancy, school absence and wastewater testing. CONCLUSIONS: The OST surveillance reports were a valuable information resource used by local stakeholders in their response to the SARS-CoV-2 epidemic. Control measures that affect disease epidemiology and monitoring requirements need to be considered in the continuous maintenance of surveillance outputs. We identified areas for further development and, since the evaluation, information on repeat infections and vaccination data have been included in the surveillance reports. Furthermore, timeliness of publications has been improved by updating the data flow pathways.

Accessible health care is critical to the effective control of sexually transmitted infections.

Bacterial sexually transmitted infections (STIs) are rising relentlessly in virtually every country and among most risk groups. These infections have substantial individual and community consequences and costs. This review summarises the evidence for the effectiveness of different strategies to control STIs and assumes countries have sufficient financial resources to provide accessible health care. Reducing the probability of transmission essentially involves increasing condom use, which is problematic given that condom use is currently falling in most risk groups. Interventions to increase condom use are expensive and hard to sustain. Only a limited number of studies have shown it is possible to reduce the rate of partner change and sustained changes are difficult. In contrast, the provision of accessible health care has a powerful effect on the incidence rate of STIs, with dramatic falls in STIs in virtually all countries following the discovery of antibiotics. More recent studies support the powerful role of accessible health care as a strategy for putting substantial downward pressure on STI rates. Accessible health care has a powerful effect on the incidence of STIs. The professionals who are responsible for funding these services need to appreciate that they are ultimately responsible for the rates of STIs in their communities. In contrast, personal behaviour plays a less powerful role in determining the incidence of STIs and is hard to change and sustain at a population level. The public needs to appreciate that it is the governments they elect and not individuals who are responsible for the rates of STIs in their communities.

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.

Prevalence of new variants of Chlamydia trachomatis escaping detection by the Aptima Combo 2 assay, England, June to August 2019.

We identified two new Chlamydia trachomatis (CT) variants escaping Aptima Combo 2 (AC2) assay detection, in clinical specimens of two patients. One had a C1514T mutation the other a G1523A mutation, both within the AC2 23S rRNA target region. The prevalence of such variants among persons tested for CT in England was estimated to be fewer than 0.003%.

Acceptability and potential impact of delivering sexual health promotion information through social media and dating apps to MSM in England: a qualitative study.

BACKGROUND: Increasing rates of sexually transmitted infections (STIs) in men-who-have-sex-with-men (MSM) in England is a pressing public health concern. Interventions targeting MSM, including information provision that effectively promotes sexual health, are needed. To support such intervention development, it is necessary to understand acceptable ways of delivering sexual health information. We explored the acceptability and potential uses and impacts of delivering sexual health information to MSM through social media and geosocial networking apps or dating apps. METHODS: Semi-structured interviews were conducted in person or by telephone with 25 MSM resident in England recruited via dating apps and social media advertisements. Interviews explored sexual health information sources, perceptions and uses. Attitudes towards sexual health promotion through social media and dating apps were then discussed. The data were analysed using thematic analysis. RESULTS: Sexual health information delivery through social media and dating apps was considered acceptable. Receiving information when browsing social media was viewed positively by most, as people have time to absorb information. In contrast, concerns were expressed that sharing or commenting on social media sexual health information may lead to judgements and discrimination. While social media reaches a high proportion of the population, dating apps can easily target MSM. However, tensions exist between the ability to provide information at an opportune time through dating apps, when users are connecting with new sexual partners, with the potential to adversely affect the app user's experience. Hypothetical and actual uses and impacts of sexual health information ranged from no impact to reading information, sharing with peers, and increased awareness, to influencing healthcare-seeking, decision-making and risk-taking behaviours. Ensuring that information is engaging, positive in tone, not too clinical, focused on building social norms and delivered by trusted organisations were viewed as important for supporting its use. CONCLUSIONS: Overall, these findings support the development of new interventions that use dating apps and social media for sexual health promotion.

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.

Spatial clusters of gonorrhoea in England with particular reference to the outcome of partner notification: 2012 and 2013.

BACKGROUND: This study explored spatial-temporal variation in diagnoses of gonorrhoea to identify and quantify endemic areas and clusters in relation to patient characteristics and outcomes of partner notification (PN) across England, UK. METHODS: Endemic areas and clusters were identified using a two-stage analysis with Kulldorff's scan statistics (SaTScan). RESULTS: Of 2,571,838 tests, 53,547 diagnoses were gonorrhoea positive (positivity = 2.08%). The proportion of diagnoses in heterosexual males was 1.5 times that in heterosexual females. Among index cases, men who have sex with men (MSM) were 8 times more likely to be diagnosed with gonorrhoea than heterosexual males (p<0.0001). After controlling for age, gender, ethnicity and deprivation rank, 4 endemic areas were identified including 11,047 diagnoses, 86% of which occurred in London. 33 clusters included 17,629 diagnoses (34% of total diagnoses in 2012 and 2013) and spanned 21 locations, some of which were dominated by heterosexually acquired infection, whilst others were MSM focused. Of the 53,547 diagnoses, 14.5% (7,775) were the result of PN. The proportion of patients who attended services as a result of PN varied from 0% to 61% within different age, gender and sexual orientation cohorts. A third of tests resulting from PN were positive for gonorrhoea. 25% of Local Authorities (n = 81, 95% CI: 20.2, 29.5) had a higher than expected proportion for female PN diagnoses as compared to 16% for males (n = 52, 95% CI: 12.0, 19.9). CONCLUSIONS: The English gonorrhoea epidemic is characterised by spatial-temporal variation. PN success varied between endemic areas and clusters. Greater emphasis should be placed on the role of PN in the control of gonorrhoea to reduce the risk of onward transmission, re-infection, and complications of infection.

What is the overlap between HIV and shigellosis epidemics in England: further evidence of MSM transmission?

BACKGROUND: Evidence suggests that sexual transmission between men has replaced foreign travel as the predominant mode of Shigella transmission in England. However, sexuality and HIV status are not routinely recorded for laboratory-reported Shigella, and the role of HIV in the Shigella epidemic is not well understood. METHODS: The Modular Open Laboratory Information System containing all Shigella cases reported to Public Health England (PHE) and the PHE HIV and AIDS Reporting System holding all adults living with diagnosed HIV in England were matched using a combination of Soundex code, date of birth and gender. RESULTS: From 2004 to 2015, 88 664 patients were living with HIV, and 10 269 Shigella cases were reported in England; 9% (873/10 269) of Shigella cases were diagnosed with HIV, of which 93% (815/873) were in men. Shigella cases without reported travel history were more likely to be living with HIV than those who had travelled (14% (751/5427) vs 3% (134/4854); p<0.01). From 2004 to 2015, the incidence of Shigella in men with HIV rose from 47/100 000 to 226/100 000 (p<0.01) peaking in 2014 at 265/100 000, but remained low in women throughout the study period (0-24/100 000). Among Shigella cases without travel and with HIV, 91% (657/720) were men who have sex with men (MSM). HIV preceded Shigella diagnosis in 86% (610/720), and 65% (237/362) had an undetectable viral load (<50 copies/mL). DISCUSSION: We observed a sustained increase in the national rate of shigellosis in MSM with HIV, who may experience more serious clinical disease. Sexual history, HIV status and STI risk might require sensitive investigation in men presenting with gastroenteritis.

Factors associated with four atypical cases of congenital syphilis in England, 2016 to 2017: an ecological analysis.

Four isolated cases of congenital syphilis born to mothers who screened syphilis negative in the first trimester were identified between March 2016 and January 2017 compared with three cases between 2010 and 2015. The mothers were United Kingdom-born and had no syphilis risk factors. Cases occurred in areas with recent increases in sexually-transmitted syphilis among women and men who have sex with men, some behaviourally bisexual, which may have facilitated bridging between sexual networks.

Outbreak of hepatitis A associated with men who have sex with men (MSM), England, July 2016 to January 2017.

Between July 2016 and January 2017, 37 confirmed cases of hepatitis A with two unique IA genotype strains primarily among men who have sex with men, were reported across eight areas in England and Northern Ireland. Epidemiological and laboratory investigations indicate that these strains may have been imported several times from Spain, with secondary sexual transmission in the United Kingdom. Local and national public health services are collaborating to control this ongoing outbreak.

Proportion of Pelvic Inflammatory Disease Cases Caused by Chlamydia trachomatis: Consistent Picture From Different Methods.

BACKGROUND: Pelvic inflammatory disease (PID) is a leading cause of both tubal factor infertility and ectopic pregnancy. Chlamydia trachomatis is an important risk factor for PID, but the proportion of PID cases caused by C. trachomatis is unclear. Estimates of this are required to evaluate control measures. METHODS: We consider 5 separate methods of estimating age-group-specific population excess fractions (PEFs) of PID due to C. trachomatis, using routine data, surveys, case-control studies, and randomized controlled trials, and apply these to data from the United Kingdom before introduction of the National Chlamydia Screening Programme. RESULTS: As they are informed by randomized comparisons and national exposure and outcome estimates, our preferred estimates of the proportion of PID cases caused by C. trachomatis are 35% (95% credible interval [CrI], 11%-69%) in women aged 16-24 years and 20% (95% CrI, 6%-38%) in women aged 16-44 years in the United Kingdom. There is a fair degree of consistency between adjusted estimates of PEF, but all have wide 95% CrIs. The PEF decreases from 53.5% (95% CrI, 15.6%-100%) in women aged 16-19 years to 11.5% (95% CrI, 3.0%-25.7%) in women aged 35-44 years. CONCLUSIONS: The PEFs of PID due to C. trachomatis decline steeply with age by a factor of around 5-fold between younger and older women. Further studies of the etiology of PID in different age groups are required.

Identifying and interpreting spatiotemporal variation in diagnoses of infectious syphilis among men, England: 2009 to 2013.

OBJECTIVES: Spatial clusters and variations in the trajectory of local epidemics were explored in relation to sexual orientation, demographic factors, stage of syphilis infection and HIV serostatus. METHODS: Kulldorff's scan statistics (SaTScan) was used to distinguish endemic and temporary clusters using a two-stage analysis. RESULTS: Endemic areas were found in London, Manchester, Brighton and Blackpool. Up to 40% of diagnoses were found within an 11 km radius of central London. Of men diagnosed with syphilis in London, 80% were men who have sex with men (MSM). Annual incidence in London increased from 24 cases (95% CI 23 to 26) per 100 000 male population in 2009 to 36 cases (95% CI 34 to38) in 2013. In comparison with clusters, endemic areas were characterised by a significantly higher (p<0.05) proportion of MSM (83% compared with 73%), increased HIV positivity (41% vs 15%), age 35 to 44 years (34% vs 23%), a lower proportion of patients born in the UK (50% vs 79%) and a lower proportion of primary stage infection (40% vs 47%). Space-time clusters outside endemic areas occurred in urban and rural areas and diagnoses fluctuated below 10 per month. Exponential increases in diagnoses resembling point source outbreaks were seen at two locations. CONCLUSION: Control of syphilis in endemic areas has proved elusive and clusters present unique intervention opportunities. Investigating the diversity of local epidemics provides information that can be used to predict outbreak structure, plan and evaluate sexual health services and guide public health investigation, hypothesis generation and research.

The natural history of Chlamydia trachomatis infection in women: a multi-parameter evidence synthesis.

BACKGROUND AND OBJECTIVES: The evidence base supporting the National Chlamydia Screening Programme, initiated in 2003, has been questioned repeatedly, with little consensus on modelling assumptions, parameter values or evidence sources to be used in cost-effectiveness analyses. The purpose of this project was to assemble all available evidence on the prevalence and incidence of Chlamydia trachomatis (CT) in the UK and its sequelae, pelvic inflammatory disease (PID), ectopic pregnancy (EP) and tubal factor infertility (TFI) to review the evidence base in its entirety, assess its consistency and, if possible, arrive at a coherent set of estimates consistent with all the evidence. METHODS: Evidence was identified using 'high-yield' strategies. Bayesian Multi-Parameter Evidence Synthesis models were constructed for separate subparts of the clinical and population epidemiology of CT. Where possible, different types of data sources were statistically combined to derive coherent estimates. Where evidence was inconsistent, evidence sources were re-interpreted and new estimates derived on a post-hoc basis. RESULTS: An internally coherent set of estimates was generated, consistent with a multifaceted evidence base, fertility surveys and routine UK statistics on PID and EP. Among the key findings were that the risk of PID (symptomatic or asymptomatic) following an untreated CT infection is 17.1% [95% credible interval (CrI) 6% to 29%] and the risk of salpingitis is 7.3% (95% CrI 2.2% to 14.0%). In women aged 16-24 years, screened at annual intervals, at best, 61% (95% CrI 55% to 67%) of CT-related PID and 22% (95% CrI 7% to 43%) of all PID could be directly prevented. For women aged 16-44 years, the proportions of PID, EP and TFI that are attributable to CT are estimated to be 20% (95% CrI 6% to 38%), 4.9% (95% CrI 1.2% to 12%) and 29% (95% CrI 9% to 56%), respectively. The prevalence of TFI in the UK in women at the end of their reproductive lives is 1.1%: this is consistent with all PID carrying a relatively high risk of reproductive damage, whether diagnosed or not. Every 1000 CT infections in women aged 16-44 years, on average, gives rise to approximately 171 episodes of PID and 73 of salpingitis, 2.0 EPs and 5.1 women with TFI at age 44 years. CONCLUSIONS AND RESEARCH RECOMMENDATIONS: The study establishes a set of interpretations of the major studies and study designs, under which a coherent set of estimates can be generated. CT is a significant cause of PID and TFI. CT screening is of benefit to the individual, but detection and treatment of incident infection may be more beneficial. Women with lower abdominal pain need better advice on when to seek early medical attention to avoid risk of reproductive damage. The study provides new insights into the reproductive risks of PID and the role of CT. Further research is required on the proportions of PID, EP and TFI attributable to CT to confirm predictions made in this report, and to improve the precision of key estimates. The cost-effectiveness of screening should be re-evaluated using the findings of this report. FUNDING: The Medical Research Council grant G0801947.

Which sexually active young female students are most at risk of pelvic inflammatory disease? A prospective study.

OBJECTIVE: To identify risk factors for pelvic inflammatory disease (PID) in female students. METHODS: We performed a prospective study set in 11 universities and 9 further education colleges in London. In 2004-2006, 2529 sexually experienced, multiethnic, female students, mean age 20.8 years, provided self-taken vaginal samples and completed questionnaires at recruitment to the Prevention of Pelvic Infection chlamydia screening trial. After 12 months, they were followed up by questionnaire backed by medical record search and assessed for PID by blinded genitourinary medicine physicians. RESULTS: Of 2004 (79%) participants who reported numbers of sexual partners during follow-up, 32 (1.6%, 95% CI 1.1% to 2.2%) were diagnosed with PID. The strongest predictor of PID was baseline Chlamydia trachomatis (relative risk (RR) 5.7, 95% CI 2.6 to 15.6). After adjustment for baseline C. trachomatis, significant predictors of PID were ≥2 sexual partners or a new sexual partner during follow-up (RR 4.0, 95% CI 1.8 to 8.5; RR 2.8, 95% CI 1.3 to 6.3), age <20 years (RR 3.3, 95% CI 1.5 to 7.0), recruitment from a further education college rather than a university (RR 2.6, 95% CI 1.3 to 5.3) and history at baseline of vaginal discharge (RR 2.7, 95% CI 1.2 to 5.8) or pelvic pain (RR 4.1, 95% CI 2.0 to 8.3) in the previous six months. Bacterial vaginosis and Mycoplasma genitalium infection were no longer significantly associated with PID after adjustment for baseline C. trachomatis. CONCLUSIONS: Multiple or new partners in the last 12 months, age <20 years and attending a further education college rather than a university were risk factors for PID after adjustment for baseline C. trachomatis infection. Sexual health education and screening programmes could be targeted at these high-risk groups. TRIAL REGISTRATION NUMBER: (ClinicalTrials.gov NCT00115388).

Rapid increase in lymphogranuloma venereum in men who have sex with men, United Kingdom, 2003 to September 2015.

United Kingdom (UK) national data show a sharp increase in diagnoses of lymphogranuloma venereum (LGV) since 2012. Most cases are in men who have sex with men (MSM) living in London, with high rates of co-infection with HIV and other sexually transmitted infections. In light of these data, and the recent finding that one quarter of LGV infections may be asymptomatic, clinicians should be vigilant in testing for LGV, including in asymptomatic HIV-positive MSM.

Characteristics of LGV repeaters: analysis of LGV surveillance data.

OBJECTIVES: A number of individuals have acquired lymphogranuloma venereum (LGV) infection multiple times since its re-emergence. We describe the characteristics of reinfections and those who acquire them. METHODS: The LGV Enhanced Surveillance system collected detailed information on LGV episodes in the U.K. from 2004 to 2010. Using logistic regression we compared the baseline characteristics of men who have sex with men (MSM) who had a repeat LGV episode ('repeaters') to MSM with a single reported episode ('non-repeaters'). RESULTS: There were 66 individuals among the 1281 MSM (5.2%) with LGV episode who had a recorded reinfection during the data collection period. Those who acquired LGV reinfection were more likely to be HIV positive (97% vs 79%), visit a clinic in London (OR 2.0, 95% CI 1.1 to 3.8), and have hepatitis C (OR 2.2, 95% CI 1.1 to 4.6) or concurrent gonorrhoea (OR 2.2, 95% CI 1.2 to 3.8) on their first recorded LGV episode. Repeaters reported higher levels of unprotected sex, but behavioural variables were not significantly different between repeaters and non-repeaters. CONCLUSIONS: Among LGV repeaters, risk behaviour alone did not explain subsequent reinfection. LGV repeaters have a high level of other sexually transmitted infections (STIs) which may be linked to their central position in the sexual network that contributes to their heightened risk of STI acquisition. Given the low prevalence of LGV in the general MSM population, momentary increases in incidence in subsets of the population may be an important factor for LGV risk where the overall level of sexual risk behaviour is higher. Validating this would require research into sexual network structures.

Challenges Presented by Re-Emerging Sexually Transmitted Infections in HIV Positive Men who have Sex with Men: An Observational Study of Lymphogranuloma Venereum in the UK.

BACKGROUND: United Kingdom has reported the largest documented outbreak of lymphogranuloma venereum (LGV), a re-emerging sexually transmitted infection (STI) which is primarily seen in HIV-positive men who have sex with men (MSM). A diagnostic service was established in response to the outbreak linked to a voluntary LGV Enhanced Surveillance system. We examined the performance of this novel surveillance system to identify utility in tracking a re-emerging infection. METHODS: We described laboratory data on samples and surveillance data from case reports for LGV from 2004-2010. We performed a cross-sectional analysis comparing clinical and behavioural characteristics of HIV-positive and HIV-negative/unknown LGV cases diagnosed in MSM using multivariable logistic regression models with generalised estimating equations to control for repeat infections. RESULTS: LGV Surveillance data were available for 87% (1,370/1,581) of LGV cases (after de-duplication). There were 1,342 episodes in 1,281 MSM, most of whom were known to be HIV-positive (1,028/1,281, 80.2%,). HIV-positive men reported a shorter duration of symptoms (aOR 0.5; 95%CI 0.3, 0.8 for reporting more than a week compared to a week or less) in comparison to HIV-negative/unknown MSM, and were more likely to report unprotected receptive anal intercourse (aOR 2.7; 95% CI 1.3, 5.8). CONCLUSION: The surveillance identified the population at greater risk of infection based on higher levels of risk behaviour in HIV-positive LGV cases. However, there was diagnostic bias towards HIV-positive LGV cases who presented with a shorter duration of symptoms when compared to HIV-negative/unknown LGV cases.