Inequalities in sexual and reproductive outcomes among women aged 16-24 in England (2012-2019).

BACKGROUND: Women aged 16-24 in England have a high burden of sexual and reproductive morbidity, with particularly poor outcomes among people living in more deprived areas (including racially minoritised populations). This analysis used national data to examine the disparities within sexual and reproductive outcomes among this population and to assess whether the patterns of inequality were consistent across all outcomes. METHODS: Within this ecological study, univariable and multivariable Poisson regression analyses of neighbourhood-level data from national data sets were carried out to investigate the relationships of deprivation and ethnicity with each of six dependent variables: gonorrhoea and chlamydia testing rates, gonorrhoea and chlamydia test positivity rates, and abortion and repeat abortion rates. RESULTS: When comparing Index of Multiple Deprivation (IMD) decile 1 (most deprived) and IMD decile 10 (least deprived), chlamydia (RR 0.65) and gonorrhoea (0.79) testing rates, chlamydia (0.70) and gonorrhoea (0.34) positivity rates, abortion rates (0.45) and repeat abortion rates (0.72) were consistently lower in IMD decile 10 (least deprived). Similarly, chlamydia (RR 1.24) and gonorrhoea positivity rates (1.92) and repeat abortion rates (1.31) were higher among black women than white women. Results were similar when both ethnicity and deprivation were incorporated into multivariable analyses. CONCLUSION: We found similar patterns of outcome inequality across a range of sexual and reproductive outcomes, despite multiple differences in the drivers of each outcome. Our analysis suggests that there are broad structural causes of inequality across sexual and reproductive health that particularly impact the health of deprived and black populations.

Rebound of Gonorrhea after Lifting of COVID-19 Preventive Measures, England.

After lifting of all COVID-19 preventive measures in England in July 2021, marked, widespread increases in gonorrhea diagnoses, but not testing numbers, were observed, particularly in persons 15-24 years of age. Continued close surveillance and public health messaging to young persons are needed to control and prevent gonorrhea transmission.

STI testing, diagnoses and online chlamydia self-sampling among young people during the first year of the COVID-19 pandemic in England.

PURPOSE: COVID-19 control measures reduced face-to-face appointments at sexual health services (SHSs). Remote access to SHSs through online self-sampling was increased. This analysis assesses how these changes affected service use and STI testing among 15-24 year olds ('young people') in England. METHODS: Data on all chlamydia, gonorrhoea and syphilis tests from 2019-2020, among English-resident young people were obtained from national STI surveillance datasets. We calculated proportional differences in tests and diagnoses for each STI, by demographic characteristics, including socioeconomic deprivation, between 2019-2020. Binary logistic regression was used to determine crude and adjusted odds ratios (OR) between demographic characteristics and being tested for chlamydia by an online service. RESULTS: Compared to 2019, there were declines in testing (chlamydia-30%; gonorrhoea-26%; syphilis-36%) and diagnoses (chlamydia-31%; gonorrhoea-25%; syphilis-23%) among young people in 2020. Reductions were greater amongst 15-19 year-olds vs. 20-24 year-olds. Amongst people tested for chlamydia, those living in the least deprived areas were more likely to be tested using an online self-sampling kit (males; OR = 1.24 [1.22-1.26], females; OR = 1.28 [1.27-1.30]). CONCLUSION: The first year of the COVID-19 pandemic in England saw declines in STI testing and diagnoses in young people and disparities in the use of online chlamydia self-sampling which risk widening existing health inequalities.

Evaluating the population impact of hepatitis C direct acting antiviral treatment as prevention for people who inject drugs (EPIToPe) - a natural experiment (protocol).

INTRODUCTION: Hepatitis C virus (HCV) is the second largest contributor to liver disease in the UK, with injecting drug use as the main risk factor among the estimated 200 000 people currently infected. Despite effective prevention interventions, chronic HCV prevalence remains around 40% among people who inject drugs (PWID). New direct-acting antiviral (DAA) HCV therapies combine high cure rates (>90%) and short treatment duration (8 to 12 weeks). Theoretical mathematical modelling evidence suggests HCV treatment scale-up can prevent transmission and substantially reduce HCV prevalence/incidence among PWID. Our primary aim is to generate empirical evidence on the effectiveness of HCV 'Treatment as Prevention' (TasP) in PWID. METHODS AND ANALYSIS: We plan to establish a natural experiment with Tayside, Scotland, as a single intervention site where HCV care pathways are being expanded (including specialist drug treatment clinics, needle and syringe programmes (NSPs), pharmacies and prison) and HCV treatment for PWID is being rapidly scaled-up. Other sites in Scotland and England will act as potential controls. Over 2 years from 2017/2018, at least 500 PWID will be treated in Tayside, which simulation studies project will reduce chronic HCV prevalence among PWID by 62% (from 26% to 10%) and HCV incidence will fall by approximately 2/3 (from 4.2 per 100 person-years (p100py) to 1.4 p100py). Treatment response and re-infection rates will be monitored. We will conduct focus groups and interviews with service providers and patients that accept and decline treatment to identify barriers and facilitators in implementing TasP. We will conduct longitudinal interviews with up to 40 PWID to assess whether successful HCV treatment alters their perspectives on and engagement with drug treatment and recovery. Trained peer researchers will be involved in data collection and dissemination. The primary outcome - chronic HCV prevalence in PWID - is measured using information from the Needle Exchange Surveillance Initiative survey in Scotland and the Unlinked Anonymous Monitoring Programme in England, conducted at least four times before and three times during and after the intervention. We will adapt Bayesian synthetic control methods (specifically the Causal Impact Method) to generate the cumulative impact of the intervention on chronic HCV prevalence and incidence. We will use a dynamic HCV transmission and economic model to evaluate the cost-effectiveness of the HCV TasP intervention, and to estimate the contribution of the scale-up in HCV treatment to observe changes in HCV prevalence. Through the qualitative data we will systematically explore key mechanisms of TasP real world implementation from provider and patient perspectives to develop a manual for scaling up HCV treatment in other settings. We will compare qualitative accounts of drug treatment and recovery with a 'virtual cohort' of PWID linking information on HCV treatment with Scottish Drug treatment databases to test whether DAA treatment improves drug treatment outcomes. ETHICS AND DISSEMINATION: Extending HCV community care pathways is covered by ethics (ERADICATE C, ISRCTN27564683, Super DOT C Trial clinicaltrials.gov: NCT02706223). Ethical approval for extra data collection from patients including health utilities and qualitative interviews has been granted (REC ref: 18/ES/0128) and ISCRCTN registration has been completed (ISRCTN72038467). Our findings will have direct National Health Service and patient relevance; informing prioritisation given to early HCV treatment for PWID. We will present findings to practitioners and policymakers, and support design of an evaluation of HCV TasP in England.

Correction: Sera selected from national STI surveillance system shows Chlamydia trachomatis PgP3 antibody correlates with time since infection and number of previous infections.

[This corrects the article DOI: 10.1371/journal.pone.0208652.].

The utility of serology for elimination surveillance of trachoma.

Robust surveillance methods are needed for trachoma control and recrudescence monitoring, but existing methods have limitations. Here, we analyse data from nine trachoma-endemic populations and provide operational thresholds for interpretation of serological data in low-transmission and post-elimination settings. Analyses with sero-catalytic and antibody acquisition models provide insights into transmission history within each population. To accurately estimate sero-conversion rates (SCR) for trachoma in populations with high-seroprevalence in adults, the model accounts for secondary exposure to Chlamydia trachomatis due to urogenital infection. We estimate the population half-life of sero-reversion for anti-Pgp3 antibodies to be 26 (95% credible interval (CrI): 21-34) years. We show SCRs below 0.015 (95% confidence interval (CI): 0.0-0.049) per year correspond to a prevalence of trachomatous inflammation-follicular below 5%, the current threshold for elimination of active trachoma as a public health problem. As global trachoma prevalence declines, we may need cross-sectional serological survey data to inform programmatic decisions.

Serological and PCR-based markers of ocular Chlamydia trachomatis transmission in northern Ghana after elimination of trachoma as a public health problem.

BACKGROUND: Validation of elimination of trachoma as a public health problem is based on clinical indicators, using the WHO simplified grading system. Chlamydia trachomatis (Ct) infection and anti-Ct antibody responses (anti-Pgp3) have both been evaluated as alternative indicators in settings with varying levels of trachoma. There is a need to evaluate the feasibility of using tests for Ct infection and anti-Pgp3 antibodies at scale in a trachoma-endemic country and to establish the added value of the data generated for understanding transmission dynamics in the peri-elimination setting. METHODOLOGY/PRINCIPAL FINDINGS: Dried blood spots for serological testing and ocular swabs for Ct infection testing (taken from children aged 1-9 years) were integrated into the pre-validation trachoma surveys conducted in the Northern and Upper West regions of Ghana in 2015 and 2016. Ct infection was detected using the GeneXpert PCR platform and the presence of anti-Pgp3 antibodies was detected using both the ELISA assay and multiplex bead array (MBA). The overall mean cluster-summarised TF prevalence (the clinical indicator) was 0.8% (95% CI: 0.6-1.0) and Ct infection prevalence was 0.04% (95%CI: 0.00-0.12). Anti-Pgp3 seroprevalence using the ELISA was 5.5% (95% CI: 4.8-6.3) compared to 4.3% (95%CI: 3.7-4.9) using the MBA. There was strong evidence from both assays that seropositivity increased with age (p<0.001), although the seroconversion rate was estimated to be very low (between 1.2 to 1.3 yearly events per 100 children). CONCLUSIONS/SIGNIFICANCE: Infection and serological data provide useful information to aid in understanding Ct transmission dynamics. Elimination of trachoma as a public health problem does not equate to the absence of ocular Ct infection nor cessation in acquisition of anti-Ct antibodies.

Advancing the public health applications of Chlamydia trachomatis serology.

Genital Chlamydia trachomatis infection is the most commonly diagnosed sexually transmitted infection. Trachoma is caused by ocular infection with C trachomatis and is the leading infectious cause of blindness worldwide. New serological assays for C trachomatis could facilitate improved understanding of C trachomatis epidemiology and prevention. C trachomatis serology offers a means of investigating the incidence of chlamydia infection and might be developed as a biomarker of scarring sequelae, such as pelvic inflammatory disease. Therefore, serological assays have potential as epidemiological tools to quantify unmet need, inform service planning, evaluate interventions including screening and treatment, and to assess new vaccine candidates. However, questions about the performance characteristics and interpretation of C trachomatis serological assays remain, which must be addressed to advance development within this field. In this Personal View, we explore the available information about C trachomatis serology and propose several priority actions. These actions involve development of target product profiles to guide assay selection and assessment across multiple applications and populations, establishment of a serum bank to facilitate assay development and evaluation, and development of technical and statistical methods for assay evaluation and analysis of serological findings. The field of C trachomatis serology will benefit from collaboration across the public health community to align technological developments with their potential applications.

Serology reflects a decline in the prevalence of trachoma in two regions of The Gambia.

Trachoma is caused by Chlamydia trachomatis (Ct). It is targeted for global elimination as a public health problem. In 2014, a population-based cross-sectional study was performed in two previously trachoma-endemic areas of The Gambia. Participants of all ages from Lower River Region (LRR) (N = 1028) and Upper River Region (URR) (N = 840) underwent examination for trachoma and had blood collected for detection of antibodies against the Ct antigen Pgp3, by ELISA. Overall, 30 (1.6%) individuals had active trachoma; the prevalence in children aged 1-9 years was 3.4% (25/742) with no statistically significant difference in prevalence between the regions. There was a significant difference in overall seroprevalence by region: 26.2% in LRR and 17.1% in URR (p < 0.0001). In children 1-9 years old, seroprevalence was 4.4% in LRR and 3.9% in URR. Reversible catalytic models using information on age-specific seroprevalence demonstrated a decrease in the transmission of Ct infection in both regions, possibly reflecting the impact of improved access to water, health and sanitation as well as mass drug administration campaigns. Serological testing for antibodies to Ct antigens is potentially useful for trachoma programmes, but consideration should be given to the co-endemicity of sexually transmitted Ct infections.

Prevalence of signs of trachoma, ocular Chlamydia trachomatis infection and antibodies to Pgp3 in residents of Kiritimati Island, Kiribati.

OBJECTIVE: In some Pacific Island countries, such as Solomon Islands and Fiji, active trachoma is common, but ocular Chlamydia trachomatis (Ct) infection and trachomatous trichiasis (TT) are rare. On Tarawa, the most populous Kiribati island, both the active trachoma sign "trachomatous inflammation-follicular" (TF) and TT are present at prevalences warranting intervention. We sought to estimate prevalences of TF, TT, ocular Ct infection, and anti-Ct antibodies on Kiritimati Island, Kiribati, to assess local relationships between these parameters, and to help determine the need for interventions against trachoma on Kiribati islands other than Tarawa. METHODS: As part of the Global Trachoma Mapping Project (GTMP), on Kiritimati, we examined 406 children aged 1-9 years for active trachoma. We collected conjunctival swabs (for droplet digital PCR against Ct plasmid targets) from 1-9-year-olds with active trachoma, and a systematic selection of 1-9-year-olds without active trachoma. We collected dried blood spots (for anti-Pgp3 ELISA) from all 1-9-year-old children. We also examined 416 adults aged ≥15 years for TT. Prevalence of TF and TT was adjusted for age (TF) or age and gender (TT) in five-year age bands. RESULTS: The age-adjusted prevalence of TF in 1-9-year-olds was 28% (95% confidence interval [CI]: 24-35). The age- and gender-adjusted prevalence of TT in those aged ≥15 years was 0.2% (95% CI: 0.1-0.3%). Twenty-six (13.5%) of 193 swabs from children without active trachoma, and 58 (49.2%) of 118 swabs from children with active trachoma were positive for Ct DNA. Two hundred and ten (53%) of 397 children had anti-Pgp3 antibodies. Both infection (p<0.0001) and seropositivity (p<0.0001) were strongly associated with active trachoma. In 1-9-year-olds, the prevalence of anti-Pgp3 antibodies rose steeply with age. CONCLUSION: Trachoma presents a public health problem on Kiritimati, where the high prevalence of ocular Ct infection and rapid increase in seropositivity with age suggest intense Ct transmission amongst young children. Interventions are required here to prevent future blindness.

Defining Seropositivity Thresholds for Use in Trachoma Elimination Studies.

BACKGROUND: Efforts are underway to eliminate trachoma as a public health problem by 2020. Programmatic guidelines are based on clinical signs that correlate poorly with Chlamydia trachomatis (Ct) infection in post-treatment and low-endemicity settings. Age-specific seroprevalence of anti Ct Pgp3 antibodies has been proposed as an alternative indicator of the need for intervention. To standardise the use of these tools, it is necessary to develop an analytical approach that performs reproducibly both within and between studies. METHODOLOGY: Dried blood spots were collected in 2014 from children aged 1-9 years in Laos (n = 952) and Uganda (n = 2700) and from people aged 1-90 years in The Gambia (n = 1868). Anti-Pgp3 antibodies were detected by ELISA. A number of visual and statistical analytical approaches for defining serological status were compared. PRINCIPAL FINDINGS: Seroprevalence was estimated at 11.3% (Laos), 13.4% (Uganda) and 29.3% (The Gambia) by visual inspection of the inflection point. The expectation-maximisation algorithm estimated seroprevalence at 10.4% (Laos), 24.3% (Uganda) and 29.3% (The Gambia). Finite mixture model estimates were 15.6% (Laos), 17.1% (Uganda) and 26.2% (The Gambia). Receiver operating characteristic (ROC) curve analysis using a threshold calibrated against external reference specimens estimated the seroprevalence at 6.7% (Laos), 6.8% (Uganda) and 20.9% (The Gambia) when the threshold was set to optimise Youden's J index. The ROC curve analysis was found to estimate seroprevalence at lower levels than estimates based on thresholds established using internal reference data. Thresholds defined using internal reference threshold methods did not vary substantially between population samples. CONCLUSIONS: Internally calibrated approaches to threshold specification are reproducible and consistent and thus have advantages over methods that require external calibrators. We propose that future serological analyses in trachoma use a finite mixture model or expectation-maximisation algorithm as a means of setting the threshold for ELISA data. This will facilitate standardisation and harmonisation between studies and eliminate the need to establish and maintain a global calibration standard.

Community seroprevalence survey for yaws and trachoma in the Western Division of Fiji.

BACKGROUND: Both yaws and trachoma are endemic in several countries in the Pacific. In co-endemic countries there may be potential synergies between both control programmes. METHODS: We undertook a cluster randomised trachoma and yaws seroprevalence survey of children in the Western Division of Fiji. Children were examined for skin lesions consistent with active yaws. A dried blood spot was collected which was tested using the Treponema pallidum particle agglutination (TPPA) test and an ELISA to detect antibodies against Pgp3. RESULTS: A total of 607 children from 305 households across 23 villages were recruited into the survey. On skin examination, no child had clinical evidence of yaws, and the TPPA assay was negative in all children (0%, 95% CI 0.0-0.6). The seroprevalence of Pgp3 antibodies was 20.9% (95% CI 17.8-24.6%). DISCUSSION: In this study there was neither clinical nor serological evidence that transmission of yaws was ongoing. The Pgp3 seroprevalence pattern was consistent with either low level transmission of ocular Chlamydia trachomatis or exposure to C. trachomatis in the birth canal which is consistent with a survey conducted in the same region in 2013. These data suggest neither yaws nor ocular chlamydia infection are a significant public health problem in the Western Division of Fiji.

New developments in malaria diagnostics: monoclonal antibodies against Plasmodium dihydrofolate reductase-thymidylate synthase, heme detoxification protein and glutamate rich protein.

Currently available rapid diagnostic tests (RDTs) for malaria show large variation in sensitivity and specificity, and there are concerns about their stability under field conditions. To improve current RDTs, monoclonal antibodies (mAbs) for novel malaria antigens have been developed and screened for their possible use in new diagnostic tests. Three antigens, glutamate rich protein (GLURP), dihydrofolate reductase-thymidylate synthase (DHFR-TS) and heme detoxification protein (HDP), were selected based on literature searches. Recombinant antigens were produced and used to immunize mice. Antibody-producing cell lines were subsequently selected and the resulting antibodies were screened for specificity against Plasmodium falciparum and Plasmodium vivax. The most optimal antibody couples were selected based on antibody affinity (expressed as dissociation constants, KD) and detection limit of crude antigen extract from P. falciparum 3D7 culture. The highest affinity antibodies have KD values of 0.10 nM ± 0.014 (D5) and 0.068 ± 0.015 nM (D6) for DHFR-TS mAbs, 0.10 ± 0.022 nM (H16) and 0.21 ± 0.022 nM (H18) for HDP mAbs and 0.11 ± 0.028 nM (G23) and 0.33 ± 0.093 nM (G22) for GLURP mAbs. The newly developed antibodies performed at least as well as commercially available histidine rich protein antibodies (KD of 0.16 ± 0.13 nM for PTL3 and 1.0 ± 0.049 nM for C1-13), making them promising reagents for further test development.

Human African trypanosomiasis: a review of non-endemic cases in the past 20 years.

Human African trypanosomiasis (HAT) is caused by sub-species of the parasitic protozoan Trypanosoma brucei and is transmitted by tsetse flies, both of which are endemic only to sub-Saharan Africa. Several cases have been reported in non-endemic areas, such as North America and Europe, due to travelers, ex-patriots or military personnel returning from abroad or due to immigrants from endemic areas. In this paper, non-endemic cases reported over the past 20 years are reviewed; a total of 68 cases are reported, 19 cases of Trypanosoma brucei gambiense HAT and 49 cases of Trypanosoma brucei rhodesiense HAT. Patients ranged in age from 19 months to 72 years and all but two patients survived. Physicians in non-endemic areas should be aware of the signs and symptoms of this disease, as well as methods of diagnosis and treatment, especially as travel to HAT endemic areas increases. We recommend extension of the current surveillance systems such as TropNetEurop and maintaining and promotion of existing reference centers of diagnostics and expertise. Important contact information is also included, should physicians require assistance in diagnosing or treating HAT.