No widespread dissemination of Chlamydia trachomatis diagnostic-escape variants and the impact of Neisseria gonorrhoeae positivity on the Aptima Combo 2 assay.

OBJECTIVES: A Finnish Chlamydia trachomatis (CT) new variant was detected in 2019 that escaped detection in the Hologic Aptima Combo 2 (AC2) assay due to a C1515T mutation in the CT 23S rRNA target region. Reflex testing of CT-negative/CT-equivocal specimens as well as those positive for Neisseria gonorrhoeae (NG) with the Hologic Aptima CT (ACT) assay was recommended to identify any CT variants. METHODS: From June to October 2019, specimens with discrepant AC2/ACT CT results were submitted to Public Health England and screened for detectable CT DNA using an inhouse real-time (RT)-PCR. When enough DNA was present, partial CT 23S rRNA gene sequencing was performed. Analysis of available relative light units and interpretative data was performed. RESULTS: A total of 317 discordant AC2/ACT specimens were collected from 315 patients. Three hundred were tested on the RT-PCR; 53.3% (n=160) were negative and 46.7% (n=140) were positive. Due to low DNA load in most specimens, sequencing was successful for only 36 specimens. The CT 23S rRNA wild-type sequence was present in 32 specimens, and two variants with C1514T or G1523A mutation were detected in four specimens from three patients. Of the discordant specimens with NG interpretation, 36.6% of NG-negative/CT-negative AC2 specimens had detectable CT DNA on the inhouse RT-PCR vs 53.3% of NG-positive/CT-negative specimens. CONCLUSIONS: No widespread dissemination of AC2 diagnostic-escape CT variants has occurred in England. We however identified the impact of NG positivity on the discordant AC2/ACT specimens; a proportion appeared due to NG positivity and the associated NG signal, rather than any diagnostic-escape variants or low DNA load. Several patients with gonorrhoea may therefore receive false-negative AC2 CT results. Single diagnostic targets and multiplex diagnostic assays have their limitations such as providing selection pressure for escape mutants and potentially reduced sensitivity, respectively. These limitations must be considered when establishing diagnostic pathways.

Molecular Epidemiology of HIV-1 Subtype B Reveals Heterogeneous Transmission Risk: Implications for Intervention and Control.

Background: The impact of HIV pre-exposure prophylaxis (PrEP) depends on infections averted by protecting vulnerable individuals as well as infections averted by preventing transmission by those who would have been infected if not receiving PrEP. Analysis of HIV phylogenies reveals risk factors for transmission, which we examine as potential criteria for allocating PrEP. Methods: We analyzed 6912 HIV-1 partial pol sequences from men who have sex with men (MSM) in the United Kingdom combined with global reference sequences and patient-level metadata. Population genetic models were developed that adjust for stage of infection, global migration of HIV lineages, and changing incidence of infection through time. Models were extended to simulate the effects of providing susceptible MSM with PrEP. Results: We found that young age <25 years confers higher risk of HIV transmission (relative risk = 2.52 [95% confidence interval, 2.32-2.73]) and that young MSM are more likely to transmit to one another than expected by chance. Simulated interventions indicate that 4-fold more infections can be averted over 5 years by focusing PrEP on young MSM. Conclusions: Concentrating PrEP doses on young individuals can avert more infections than random allocation.

Infectious disease testing of UK-bound refugees: a population-based, cross-sectional study.

BACKGROUND: The UK, like a number of other countries, has a refugee resettlement programme. External factors, such as higher prevalence of infectious diseases in the country of origin and circumstances of travel, are likely to increase the infectious disease risk of refugees, but published data is scarce. The International Organization for Migration carries out and collates data on standardised pre-entry health assessments (HA), including testing for infectious diseases, on all UK refugee applicants as part of the resettlement programme. From this data, we report the yield of selected infectious diseases (tuberculosis (TB), HIV, syphilis, hepatitis B and hepatitis C) and key risk factors with the aim of informing public health policy. METHODS: We examined a large cohort of refugees (n = 18,418) who underwent a comprehensive pre-entry HA between March 2013 and August 2017. We calculated yields of infectious diseases stratified by nationality and compared these with published (mostly WHO) estimates. We assessed factors associated with case positivity in univariable and multivariable logistic regression analysis. RESULTS: The number of refugees included in the analysis varied by disease (range 8506-9759). Overall yields were notably high for hepatitis B (188 cases; 2.04%, 95% CI 1.77-2.35%), while yields were below 1% for active TB (9 cases; 92 per 100,000, 48-177), HIV (31 cases; 0.4%, 0.3-0.5%), syphilis (23 cases; 0.24%, 0.15-0.36%) and hepatitis C (38 cases; 0.41%, 0.30-0.57%), and varied widely by nationality. In multivariable analysis, sub-Saharan African nationality was a risk factor for several infections (HIV: OR 51.72, 20.67-129.39; syphilis: OR 4.24, 1.21-24.82; hepatitis B: OR 4.37, 2.91-6.41). Hepatitis B (OR 2.23, 1.05-4.76) and hepatitis C (OR 5.19, 1.70-15.88) were associated with history of blood transfusion. Syphilis (OR 3.27, 1.07-9.95) was associated with history of torture, whereas HIV (OR 1521.54, 342.76-6754.23) and hepatitis B (OR 7.65, 2.33-25.18) were associated with sexually transmitted infection. Syphilis was associated with HIV (OR 10.27, 1.30-81.40). CONCLUSIONS: Testing refugees in an overseas setting through a systematic HA identified patients with a range of infectious diseases. Our results reflect similar patterns found in other programmes and indicate that the yields for infectious diseases vary by region and nationality. This information may help in designing a more targeted approach to testing, which has already started in the UK programme. Further work is needed to refine how best to identify infections in refugees, taking these factors into account.

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.

HTLV seroprevalence in people using HIV pre-exposure prophylaxis in England.

OBJECTIVES: HTLV-1 is predominantly a sexually-transmitted infection but testing is not mentioned in HIV-PrEP guidelines. We ascertained HTLV-1/HTLV-2 seroprevalence amongst HIV-PrEP users in England. METHODS: An unlinked anonymous seroprevalence study. RESULTS: Amongst 2015 HIV-PrEP users, 95% were men, 76% of white ethnicity and 83% had been born in Europe. There were no HTLV-1/HTLV-2 seropositive cases (95% confidence interval 0% - 0.18%). CONCLUSIONS: There were no HTLV positive cases, likely reflecting the demographic of mostly white and European-born individuals. Similar studies are needed worldwide to inform public health recommendations for HIV-PrEP using populations, particularly in HTLV-endemic settings.

Can remote STI/HIV testing and eClinical Care be compatible with robust public health surveillance?

In this paper we outline the current data capture systems for human immunodeficiency virus (HIV) and sexually transmitted infection (STI) surveillance used by Public Health England (PHE), and how these will be affected by the introduction of novel testing platforms and changing patient pathways. We outline the Chlamydia Online Clinical Care Pathway (COCCP), developed as part of the Electronic Self-Testing for Sexually Transmitted Infections (eSTI2) Consortium, which ensures that surveillance data continue to be routinely collected and transmitted to PHE. We conclude that both novel diagnostic testing platforms and established data capture systems must be adaptable to ensure continued robust public health surveillance.

Modelling the HIV epidemic among MSM in the United Kingdom: quantifying the contributions to HIV transmission to better inform prevention initiatives.

OBJECTIVES: HIV is a major public health problem among MSM in the United Kingdom with around 2400 new infections annually. We quantified the contribution of biological and behavioural factors. DESIGN: Modelling study. METHODS: A partnership-based model of HIV transmission among UK MSM aged 15-64 years was developed and calibrated to time series HIV prevalence. The calibration was validated using multiple surveillance datasets. Population-attributable fractions were used to estimate the contribution of behavioural and biological factors to HIV transmission over the period 2001-2002, 2014-2015, and 2019-2020. RESULTS: The contribution of most biological and behavioural factors was relatively constant over time, with the key group sustaining HIV transmission being higher-sexual activity MSM aged below 35 years living with undiagnosed HIV. The effect of primary HIV infection was relatively small with 2014-2015 population-attributable fraction of 10% (3-28%) in comparison with other subsequent asymptomatic stages. Diagnosed men who were not on antiretroviral therapy (ART) currently contributed 26% (14-39%) of net infections, whereas ART-treated MSM accounted for 17% (10-24%). A considerable number of new infections are also likely to occur within long-term relationships. CONCLUSION: The majority of the new HIV infections among MSM in the United Kingdom during 2001-2020 is expected to be accounted for by a small group of younger and highly sexually active individuals, living with undiagnosed HIV in the asymptomatic stage. Bringing this group into HIV/AIDS care by improving testing uptake is a vital step for preventing onward transmission and will determine the success of using ART as prevention.

Changes over calendar time in the risk of specific first AIDS-defining events following HIV seroconversion, adjusting for competing risks.

BACKGROUND: Although studies have reported large reductions in the risks of AIDS and death since the introduction of potent anti-retroviral therapies, few have evaluated whether this has been similar for all AIDS-defining diseases. We wished to evaluate changes over time in the risk of specific AIDS-defining diseases, as first events, using data from individuals with known dates of HIV seroconversion. METHODS: Using a competing risks proportional hazards model on pooled data from 20 cohorts (CASCADE), we evaluated time from HIV seroconversion to each first AIDS-defining disease (16 groups) and to death without AIDS for four calendar periods, adjusting for exposure category, age, sex, acute infection, and stratifying by cohort. We compared results to those obtained from a cause-specific hazards model. RESULTS: Of 6,941, 2,021 (29%) developed AIDS and 437 (6%) died without AIDS. The risk of AIDS or death remained constant to 1996 then reduced; relative hazard = 0.89 (95% CI: 0.77-1.03); 0.90 (95% CI: 0.81-1.01); and 0.32 (95% CI: 0.28-0.37) for 1979-1990, 1991-1993, and 1997-2001, respectively, compared to 1994-1996. Significant risk reductions in 1997-2001 were observed in all but two AIDS-defining groups and death without AIDS in a competing risks model (with similar results from a cause-specific model). There was significant heterogeneity in the risk reduction across events; from 96% for cryptosporidiosis, to 17% for death without AIDS (P < 0.0001). CONCLUSION: These findings suggest that studies reporting a stable trend for particular AIDS diseases over the period 1979-2001 may not have accounted for the competing risks among other events or lack the power to detect smaller trends.

Social deprivation and hospital admission for respiratory infection: an ecological study.

STUDY OBJECTIVE: To examine the relationship between social deprivation and risk of hospital admission for respiratory infection. METHODS AND SUBJECTS: Ecological study using hospital episode statistics and population census data. Cases were residents of the West Midlands Health Region admitted to hospital with a diagnosis of respiratory infection, acute respiratory infection, pneumonia or influenza over a 5-year period. Postcodes of cases were used to assign Townsend deprivation scores; these were then ranked and divided into five deprivation categories. Poisson regression analysis was used to estimate the magnitude of effect for associations between deprivation category and hospital admission by age and admitting diagnosis. MAIN RESULTS: There were 136755 admissions for respiratory infection, equivalent to an annual admission rate of 27.1 per 1000 population (95% CI = 26.9-27.2). Deprivation was associated with increased admission rates for all respiratory infection (P < 0.0001) and affected all age-groups. The greatest effect was in the 0-4 years age-group with admission rates 91% higher in the most deprived children compared to the least deprived. Hospital admissions for acute respiratory infection and pneumonia were both significantly associated with deprivation (P < 0.0001). CONCLUSIONS: Respiratory infection is associated with social inequalities in all age-groups, particularly in children. Prevention of respiratory infection could make an important contribution to reducing health inequalities.

Detection and response to a meningococcal disease outbreak following a youth football tournament with teams from four European countries.

An outbreak of meningococcal disease, caused by Neisseria meningitidis, occurred following an international youth football tournament in the summer of 1997, affecting individuals from four European countries. This paper describes the outbreak, focusing on international co-operation in detection, investigation, control and follow-up, identifying weaknesses and exploring opportunities for improved co-operation. Data came from interviews, reports and related documents. The detection and management of the outbreak in each country is analysed. Eleven cases were linked to this outbreak and serotyped as C:2a:P1.5. Control measures varied in each country, reflecting different national guidelines. The outbreak illustrated deficiencies in management of international outbreaks but also demonstrated benefits of international co-operation.

Establishing an enteric bacteria reference laboratory in Sierra Leone.

In 2012, Sierra Leone experienced its worst cholera outbreak in over 15 years affecting 12 of the country's 13 districts. With limited diagnostic capability, particularly in bacterial culture, the cholera outbreak was initially confirmed by microbiological testing of clinical specimens outside of Sierra Leone. During 2012 - 2013, in direct response to the lack of diagnostic microbiology facilities, and to assist in investigating and monitoring the cholera outbreak, diagnostic and reference services were established in Sierra Leone at the Central Public Health Reference Laboratory focusing specifically on isolating and identifying Vibrio cholerae and other enteric bacterial pathogens. Sierra Leone is now capable of confirming cholera cases by reference laboratory testing.

Evaluation of a modified commercial assay in detecting antibody to hepatitis C virus in oral fluids and dried blood spots.

Oral fluid testing is an effective alternative to serum antibody testing for surveillance of human immunodeficiency virus (HIV) and hepatitis B infections, and is being extended to hepatitis C infections. The objective of this study was to determine and compare the sensitivity and specificity of a modified commercial assay for the detection of antibody to hepatitis C virus (anti-HCV) in oral fluids collected by two different oral fluid collection devices (the Epitope OraSure trade mark and Sarstedt Salivette ) and in dried fingerprick blood spots. In this study, 253 anti-HCV seropositive patients and 394 blood donors (all anti-HCV negative) were recruited between August 2000 and January 2001. Each participant provided oral fluid specimens by OraSure and Salivette, and at least one dried blood spot. Serum specimens were collected from the patients whenever possible. For those injecting drug users who did not provide a serum specimen, HCV status was established on the basis of previous testing. All the nonserum samples were tested for the presence of anti-HCV, using a modified Ortho HCV 3.0 SAVe enzyme-linked immunosorbent assay (ELISA) protocol. The recommended preliminary cutoffs for the modified ELISA were suboptimal. Further, the sensitivity, specificity, and positive and negative predictive values could be improved by varying the cutoff and taking into account the likely prevalence of HCV in the population under investigation. For instance, given a population with a 50% prevalence of anti-HCV, the optimal sensitivities of the modified assay on OraSure, Salivette, and dried blood spots were 92%, 83%, and virtually 100%, respectively, in contrast to 83%, 59%, and 99% using the preliminary cutoffs. The respective optimal specificities were 99%, 93%, and 100%. In conclusion, oral fluids collected by the OraSure device provide an extremely useful method to conduct public health surveillance of not only HIV, but also hepatitis C, among injecting drug users. In addition, dried blood spot specimens may be useful for surveillance and could be employed as a first line diagnostic specimen.