Characterising HIV-Indicator conditions among two nationwide long-term cohorts of people living with HIV in Germany (1999-2023).

BACKGROUND/OBJECTIVE: Information about occurrence and affected groups of symptoms/diagnoses indicative of an HIV infection (so-called HIV indicator conditions; HIV-ICs) is lacking. We analyse HIV-IC incidence, transmission risks and immune status among people living with HIV (PLWH) antiretroviral therapy (ART) naive. METHODS: Diagnoses reported for ART-naive PLWH from two multicentre observational, prospective cohort studies between 1999-2023 were analysed. Incidence rates per 1,000 person-years (PYs) were calculated for the overall study period and time periods defined by ART treatment recommendations. For further description, CD4 counts around HIV-IC diagnosis (+ -30 days) and HIV-transmission routes were collected. RESULTS: In total 15,940 diagnoses of 18,534 PLWH in Germany were included. Of those 81% were male (median age: 36 years) and 56% reported being men, who have sex with men as the likely HIV-transmission route. Incidence rates varied between the different HIV-ICs. Syphilis had the highest incidence rate (34 per 1,000 PYs; 95% confidence interval [CI] 29-40) for sexually transmitted infections (STIs), hepatitis B was highest for viral hepatitis diagnoses (18 per 1,000 PYs; 95% CI 17-20); according to CDC-classification herpes zoster for HIV-associated diagnoses (22 per 1,000; 95% CI 20-24) and candidiasis for AIDS-defining diagnoses (30 per 1,000 PYs; 95% CI 29-32). Most PLWH with HIV-ICs (hepatitis, HIV-associated diagnoses and AIDS-defining conditions) had CD4 cell counts < 350. CONCLUSION: This analysis characterizes HIV-ICs regarding the incidence, HIV-transmission route and patients' immune status. The results underline the importance of HIV-IC-based screening to detect PLWH with already partially impaired immune status and in need of timely ART initiation.

Acceptance and feasibility of a low-threshold and substitution services-based periodical monitoring system for blood-borne and sexually transmitted infections among people who inject drugs in Germany: a mixed-methods analysis.

BACKGROUND: To reach the global elimination goals of viral hepatitis B and C (HBC, HCV), human immunodeficiency virus (HIV) and other sexually transmitted infections as a public health threat by 2030, monitoring is needed. Staff members of drug services and opioid substitution treatment (OST) practices in Berlin and Bavaria recruited clients for a pilot study addressing the respective infections among people who injected drugs (PWID) in Germany, 2021/2022. Participants filled a questionnaire and were tested for HBV, HCV, HIV and syphilis using dried blood spots (DBS). We evaluated the study design to implement a feasible and accepted nationwide periodical monitoring among PWID and serve as an example for the implementation of similar monitoring systems in other countries. METHODS: A mixed-methods design was used, including focus group discussions with study participants and staff members and a semi-quantitative questionnaire filled by the latter. Aspects covered were the setting for recruitment, study preparation for staff members, willingness of clients to participate, the study questionnaire, blood collection and return of results. RESULTS: The majority (96%) of 668 study participants were recruited in low-threshold services, drug consumption rooms and OST-practices. Flexibility of recruiting study participants during routine work or testing weeks/days was important to the facilities. Collaborations with local AIDS services helped cope with the work load of data collection. The need to train staff for DBS collection was highlighted. Study participants welcomed the testing opportunity in familiar places. Study participants frequently needed assistance to complete the study questionnaire. Return of results was considered as ethically mandatory by staff members but referral to treatment remained challenging. CONCLUSIONS: For a successful monitoring time flexibility and adequate training are essential. Individual benefits for study participants by receiving their test results should be ensured and referral networks with infectiology practices may increase number of infected PWID receiving treatment. Overall, the evaluation confirmed that a monitoring through drug services and OST-practices is feasible and well accepted in Germany. Beyond that it shows important lessons learnt for the implementation in other countries.

International harm reduction indicators are still not reached: results from a repeated cross-sectional study on drug paraphernalia distribution in Germany, 2021.

BACKGROUND: To prevent the transmission of blood-borne infections and reach the elimination of viral hepatitis by 2030, the World Health Organization (WHO) has set the goal to distribute 300 sterile needles and syringes each year per person who injects drugs (PWID). We aimed to assess drug paraphernalia distribution in Germany in 2021, including the WHO indicator, and to analyse changes to the distribution measured in 2018. METHODS: We conducted a repeated cross-sectional study of low-threshold drug services in Germany. We assessed type and quantity of distributed drug paraphernalia and the number of supplied PWID in 2021 using an online and paper-based questionnaire. We conducted a descriptive statistical analysis of data from 2021, assessed fulfillment of the WHO indicator and changes in services that participated 2021 and in the previous study 2018. RESULTS: Five hundred and eighty-nine of 1760 distributed questionnaires were returned in 2021. 204 drug services from 15 out of 16 federal states confirmed drug paraphernalia distribution, covering 20% of Germany's rural and 51% of urban counties. 108 services had also participated in 2018. The most frequently distributed paraphernalia for injecting drug use in 2021 were syringes (97% of services), needles (96%) and vitamin C (90%). Pre-cut aluminium foil (79% of services) and pipes (28%) for inhaling, and sniff tubes (43%) for nasal use were distributed less frequently. We found a median reduction in distributed syringes by 18% and by 12% for needles compared to 2018. Of 15 states, two reached the 2030 WHO-target for needles and one for syringes. CONCLUSIONS: The current national estimates and changes from 2018 to 2021 for drug paraphernalia distribution seem far from meeting the WHO target. Reasons could include a change in drug consumption behaviour towards less injecting use and more inhaling, and effects of the COVID-19 pandemic (supply difficulties, social distancing, lockdown, reduced opening hours of services). We observed pronounced regional differences in drug paraphernalia distribution. To close existing gaps, Germany should expand its drug paraphernalia distribution programmes and other harm reduction services, such as drug consumption rooms. Further investigation of determinants for adequate distribution is essential to reduce blood-borne infections in this key population.

Decreasing prevalence and stagnating incidence of Hepatitis C-co-infection among a cohort of HIV-1-positive patients, with a majority of men who have sex with men, in Germany, 1996-2019.

Co-infection with Hepatitis C virus (HCV) among HIV-positive patients leads to accelerated progression of liver disease and AIDS. Due to increased HCV prevalence and incidence, co-infection requires monitoring trends among HIV-positive individuals. This will help target prevention strategies and support to reach the global goals of eliminating viral hepatitis as a public health threat. In this analysis HCV prevalence and incidence were determined for the years 1996-2019 from yearly blood samples and questionnaire details among HIV-1-positive patients, with a majority of men who have sex with men, belonging to a nationwide, multicentre observational, prospective cohort study. The results show that HCV prevalence for acute/chronic and resolved infection increased until 2014 to 12%. Since then, prevalence of acute/chronic HCV infection rapidly decreased and prevalence of resolved infections showed a steady increase. HCV incidence was highest in 2010 and lowest in 2017; however, no significant change in HCV incidence could be seen over the years. Therefore, the introduction of directly-acting antiviral agents for HCV treatment notably decreased prevalence and potentially incidence of acute/chronic HCV infection. Nevertheless, prevalence and incidence of HCV among these HIV-1-positive study participants remain high compared with the general population and justify the need for continuous HCV prevention and treatment efforts among HIV-positive individuals.

Estimates of Toxoplasmosis Incidence Based on Healthcare Claims Data, Germany, 2011-2016.

Toxoplasmosis is a zoonotic infection contracted through Toxoplasma gondii-contaminated food, soil, or water. Seroprevalence in Germany is high, but estimates of disease incidence are scarce. We investigated incidences for various toxoplasmosis manifestations using anonymized healthcare claims data from Germany for 2011-2016. Patients with a toxoplasmosis diagnosis during the annual observational period were considered incident. The estimated incidence was adjusted to the general population age/sex distribution. We estimated an annual average of 8,047 toxoplasmosis patients in Germany. The average incidence of non-pregnancy-associated toxoplasmosis patients was 9.6/100,000 population. The incidence was highest in 2011, at 10.6 (95% CI 9.4-12.6)/100,000 population, and lowest in 2016, at 8.0 (95% CI 7.0-9.4)/100,000 population. The average incidence of toxoplasmosis during pregnancy was 40.3/100,000 pregnancies. We demonstrate a substantial toxoplasmosis disease burden in Germany. Public health and food safety authorities should implement toxoplasmosis-specific prevention programs.

Large Nationwide Outbreak of Invasive Listeriosis Associated with Blood Sausage, Germany, 2018-2019.

Invasive listeriosis is a severe foodborne infection in humans and is difficult to control. Listeriosis incidence is increasing worldwide, but some countries have implemented molecular surveillance programs to improve recognition and management of listeriosis outbreaks. In Germany, routine whole-genome sequencing, core genome multilocus sequence typing, and single nucleotide polymorphism calling are used for subtyping of Listeria monocytogenes isolates from listeriosis cases and suspected foods. During 2018-2019, an unusually large cluster of L. monocytogenes isolates was identified, including 134 highly clonal, benzalkonium-resistant sequence type 6 isolates collected from 112 notified listeriosis cases. The outbreak was one of the largest reported in Europe during the past 25 years. Epidemiologic investigations identified blood sausage contaminated with L. monocytogenes highly related to clinical isolates; withdrawal of the product from the market ended the outbreak. We describe how epidemiologic investigations and complementary molecular typing of food isolates helped identify the outbreak vehicle.

Clinical performance of the HPV DNA Array genotyping assay in detection of CIN2+ lesions with BS GP5+/6+ MPG Luminex tested cervical samples.

Human papillomavirus (HPV) detection is used for screening of cervical cancer and genotype-specific persistence has shown to be mandatory for dysplasia development. Aim of this study was to evaluate the clinical performance of HPV DNA Array for cervical intraepithelial neoplasia 2+ (CIN2+) lesion detection. HPV DNA Array is a polymerase chain reaction-based assay that targets E1 sequences of 29 HPV types (6, 11, 16, 18, 26, 31, 33, 35, 39, 40, 42, 44, 45, 51, 52, 53, 54, 56, 58, 59, 66, 67, 68, 69, 70, 73, 82, 85, and 97). The clinical evaluation was performed against the reference assay, BS-GP5+/6+ multiplex genotyping (MPG)-Luminex, with 600 cervical smear samples of a referral population. HPV DNA Array detected CIN2+ lesions with a sensitivity of 90.2%, identical to that of MPG-Luminex. Detection of CIN3+ lesions was with a sensitivity of 90.3%, as compared with 88.7% of MPG-Luminex. It demonstrated very good agreement for HPV detection, irrespective of type, of 91.5% (κ = 0.832). HPV DNA Array is a simple and robust assay, with a short protocol of 4 hours hands-on time and automated readout by ELISpot AiDot software. It permits testing of up to 96 samples in one run and may be considered for use in organized screening programs and low resource settings.

Increase in Lassa Fever Cases in Nigeria, January-March 2018.

We reviewed data pertaining to the massive wave of Lassa fever cases that occurred in Nigeria in 2018. No new virus strains were detected, but in 2018, the outbreak response was intensified, additional diagnostic support was available, and surveillance sensitivity increased. These factors probably contributed to the high case count.

CIN2+ detection of the HPV DNA Array genotyping assay in comparison with the Cobas 4800 HPV test and cytology.

BACKGROUND: HPV DNA Array is an E1-targeting PCR genotyping test, with capability of distinguishing 18 high-risk (16, 18, 26, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66, 68, 73, 82) and 11 low-risk HPV types (6, 11, 40, 42, 44, 54, 67, 69, 70, 85, 97). HPV DNA Array uses multiplex PCR for E1-gene sequence amplification. The amplicons are detected and genotyped by reverse hybridization to immobilized DNA probes spotted as triplets in single 96 well-plate wells and read by AID ELISPOT reader. METHODS: Aim of the study was to evaluate the clinical performance of the assay against internationally accepted and FDA approved Cobas 4800 HPV test (Roche Diagnostics). Study population comprised of 500 cervical samples. RESULTS: HPV DNA Array demonstrated a very high sensitivity of 100% for CIN2+ and 100% for CIN3+ detection, same as Cobas 4800. HPV DNA Array showed greater sensitivity for CIN2+ detection than cytology (100% vs. 13.6%). The agreement to Cobas 4800 for HPV detection, irrespective of type, was 81.4% with κ = 0.613. The agreement for HPV 16 was 92.8% (κ = 0.929), and for HPV 18 54.2% (κ = 0.681). CONCLUSION: HPV DNA Array demonstrated good clinical performance for detection of high-grade lesions, and may be considered for usage in a screening setting.

Analytical Evaluation of the Human Papillomavirus HPV DNA Array E1-Based Genotyping Assay.

BACKGROUND: Cervical cancer is caused by a persistent infection of human papillomavirus (HPV). Therefore, tests which detect the carcinogenic virus can be used for cervical cancer screening. OBJECTIVE: This is the first evaluation of the HPV DNA Array (AID Diagnostika, Strassberg, Germany), an E1-based genotyping polymerase chain reaction (PCR) test for identification of 29 HPV types (6, 11, 16, 18, 26, 31, 33, 35, 39, 40, 42, 44, 45, 51, 52, 53, 54, 56, 58, 59, 66, 67, 68, 69, 70, 73, 82, 85, and 97). METHODS: Analytical performance of the assay was assessed with cervical cancer cell lines with known HPV status, and preselected clinical cervical scrapings genotyped by multiplexed genotyping (MPG) with a Luminex readout (validated in-house assay). Intra- and inter-laboratory reproducibility experiments were performed to ensure the reliability of the assay. RESULTS: HPV DNA Array identified the intrinsic HPV genotype in all cervical cancer cell lines and demonstrated a high sensitivity for HPV16 probe (1 cell per PCR reaction), as well as HPV18 and 45 probes (100 cells per PCR reaction). When compared with MPG, HPV DNA Array showed a good agreement of 92.2% for HPV detection irrespective of type (κ = 0.601), and demonstrated high agreement for HPV16 (80.7%, κ = 0.836) and HPV18 (86.7%, κ = 0.925). Furthermore, high intra-/inter-laboratory reproducibility was observed (90.9-100%). CONCLUSION: HPV DNA Array showed high sensitivity for correct HPV genotype detection in experimental and clinical samples with a good correlation to the reference test. Since HPV DNA Array is based on a simple multiplexed PCR followed by reverse hybridization in a 96-well format and automated visual readout by AID ELISpot reader, it is capable of high throughput in a time-effective manner. HPV DNA Array could be considered for extended HPV genotyping of cervical smears.

Performance of OncoE6 cervical test with collection methods enabling self-sampling.

BACKGROUND: The paradigm shift from cytological screening to Human Papillomavirus (HPV)-based screening for cervical cancer allows the introduction of new technologies in sample collection and diagnostics. The OncoE6™ Cervical Test (OncoE6 Test) is a rapid, easy-to-use lateral flow method detecting HPV16/18 E6 oncoproteins that has proven to detect high-grade cervical lesions with high specificity. If compatible with self-collection samples, this technology might allow for decentralized screening of hard-to-reach populations. METHODS: For technical validation, cervicovaginal lavages were collected from 20 patients with confirmed HPV16+ or HPV18+ invasive cervical cancer. Cervical smears were collected by polyester-tipped swabs and cytobrushes. All samples were applied to the OncoE6 Test and cytobrush samples additionally genotyped. RESULTS: Lavage, swab, and cytobrush revealed concordant outcome in 18/20 samples. HPV types corresponded with the HPV genotyping by GP5+/6+ PCR analyses. Due to a rare mutation found in the E6 antibody binding site one sample was not detected, another sample had very low cellularity. CONCLUSIONS: Overall, vaginal lavages are technically adequate for the OncoE6 Test. Combining self-sampling with oncoprotein rapid testing to detect women with highest risk for severe dysplasia or cancer may allow for secondary cancer prevention in settings where other screening modalities were unsuccessful to date.

Prevalence of HIV in people with potential HIV-indicator conditions in Germany: an analysis of data from statutory health insurances.

Background: In care of people living with human immunodeficiency virus (HIV), early diagnosis of infection is one of the greatest challenges remaining. A promising approach to increase early diagnosis could be optimized HIV testing in persons with indicator conditions (ICs). ICs are conditions which are AIDS-defining in people living with HIV, conditions that may have significant adverse consequences for the individual's clinical management if the presence of HIV infection is not detected, and conditions with an (undiagnosed) HIV prevalence of ≥0.1%. Methods: In this cohort study, anonymous routine healthcare data of German statutory health insurances from 07/01/2016 to 06/30/2021 based on insured persons with an ICD-10-based diagnosis of selected ICs were analyzed. In a primary analysis, two stratifications (gender and age), and four sensitivity analyses HIV prevalence/incidence were calculated for persons with at least one of 26 IC described in international literature. This study is registered in the German Clinical Trials Register (identifier: DRKS0002874). Findings: Routine healthcare data from 513,509 insured persons were selected for analysis. In the primary analysis, only in malignant neoplasm of bronchus and lung a HIV prevalence was observed with a 95%-CI < 0.1%. ICs with particularly high HIV prevalence were pneumocystosis (40.33%), oral hairy leukoplakia (36.71%), and Kaposi's sarcoma (29.86%). When stratified by gender, it was observed that in female patients, the 95%-CI of HIV prevalence fell below 0.1% for seven ICs. No such effect was observed in male patients. Stratified by age, among patients aged 30 to <60 years, the 95%-CI of HIV prevalence were always ≥0.1%, while in the other groups the 95%-CI fell below 0.1% for several ICs. Interpretation: In samples of patients with ICs in Germany, HIV prevalences/incidences were found to be ≥0.1% for all ICs except malignant neoplasm of bronchus and lung. This confirms the classification of these conditions as ICs for the German context and emphasizes the importance of HIV testing in these populations. Funding: This analysis is part of the HIV testing recommendations in guidelines and practice study (German title of the study: "HIV-Testempfehlungen in Leitlinien und Praxis"; acronym: HeLP), which is funded by the German Federal Joint Committee as part of the Innovationsfonds program to further develop the German healthcare system (funding number 01VSF21050).

Prevalence of chronic HCV infection in EU/EEA countries in 2019 using multiparameter evidence synthesis.

Background: Epidemiological data are crucial to monitoring progress towards the 2030 Hepatitis C Virus (HCV) elimination targets. Our aim was to estimate the prevalence of chronic HCV infection (cHCV) in the European Union (EU)/European Economic Area (EEA) countries in 2019. Methods: Multi-parameter evidence synthesis (MPES) was used to produce national estimates of cHCV defined as: π = πrecρrec + πexρex + πnonρnon; πrec, πex, and πnon represent cHCV prevalence among recent people who inject drugs (PWID), ex-PWID, and non-PWID, respectively, while ρrec, ρex, and ρnon represent the proportions of these groups in the population. Information sources included the European Centre for Disease Prevention and Control (ECDC) national operational contact points (NCPs) and prevalence database, the European Monitoring Centre for Drugs and Drug Addiction databases, and the published literature. Findings: The cHCV prevalence in 29 of 30 EU/EEA countries in 2019 was 0.50% [95% Credible Interval (CrI): 0.46%, 0.55%]. The highest cHCV prevalence was observed in the eastern EU/EEA (0.88%; 95% CrI: 0.81%, 0.94%). At least 35.76% (95% CrI: 33.07%, 38.60%) of the overall cHCV prevalence in EU/EEA countries was associated with injecting drugs. Interpretation: Using MPES and collaborating with ECDC NCPs, we estimated the prevalence of cHCV in the EU/EEA to be low. Some areas experience higher cHCV prevalence while a third of prevalent cHCV infections was attributed to PWID. Further efforts are needed to scale up prevention measures and the diagnosis and treatment of infected individuals, especially in the east of the EU/EEA and among PWID. Funding: ECDC.

Optimization of HIV testing services in Germany using HIV indicator diseases: study protocol of the HeLP study.

BACKGROUND: Despite the potentially accompanying negative clinical, epidemiologic, and health economic effects, a large proportion of persons living with the human immunodeficiency virus (HIV) are diagnosed late. Internationally, numerous diseases are known to be HIV indicator diseases. Adequate HIV testing in the presence of HIV indicator diseases could help to diagnose unknown HIV infections earlier. The objective of the HeLP study is to validate published HIV indicator diseases for the German setting and to identify guidelines in terms of these indicator diseases in order to reduce knowledge gaps and increase HIV testing when HIV indicator diseases are diagnosed. METHODS: A mixed methods approach is used. In a first step, published HIV indicator diseases will be identified in a systematic literature review and subsequently discussed with clinical experts regarding their relevance for the German setting. For the validation of selected indicator diseases different data sets (two cohort studies, namely HIV-1 seroconverter study & ClinSurv-HIV, and statutory health insurance routine data) will be analyzed. Sensitivity analyses using different time periods will be performed. Guidelines of HIV indicator diseases validated in the HeLP study will be reviewed for mentioning HIV and for HIV testing recommendations. In addition, semi-standardized interviews (followed by a free discussion) with guideline creators will identify reasons why HIV testing recommendations were (not) included. Subsequently, a random sample of physicians in medical practices will be surveyed to identify how familiar physicians are with HIV testing recommendations in guidelines and, if so, which barriers are seen to perform the recommended tests in everyday care. DISCUSSION: The HeLP-study adopts the challenge to validate published HIV indicator diseases for the German setting and has the potential to close a knowledge gap regarding this objective. This has the potential to improve targeted HIV testing for patients with HIV indicator diseases and consequently lead to earlier HIV diagnosis. TRIAL REGISTRATION: DRKS00028743.

Female health-care providers' advocacy of self-sampling after participating in a workplace program for cervical cancer screening in Ghana: a mixed-methods study.

BACKGROUND: Cervical cancer is the second most common cancer among Ghanaian women and screening coverage is low. ACCESSING is a cross-sectional study investigating human papillomavirus (HPV) prevalence via self-sampling in rural communities of the North Tongu district in Ghana. Female health-care providers (HCPs) were invited to self-collect a cervicovaginal sample with a commercial sampler in order to acquaint themselves with the sampling method. OBJECTIVE: This study set out to explore female HCPs' perceptions, advocacy for, and implications of self-sampling with the aim of enhancing self-sampling acceptability in the targeted screening population. METHODS: A mixed-methods approach was used, consisting of (a) a survey among 52 female HCPs working in a district hospital and (b) 10 one-to-one semi-structured interviews with purposefully sampled HCPs. RESULTS: The quantitative analysis of the survey (n = 52) showed that, among HCPs who took the sample themselves (50/52), all found it 'Easy' or 'Very Easy' and felt 'Very Comfortable' or 'Comfortable'. 82.7% indicated that they would undertake screening more often, and 98.1% indicated they would prefer self-sampling, if cervical cancer risk is as reliably determined as by clinician-directed cytobrush sampling. All interview participants (n = 10) indicated that they appreciated the program and would recommend the screening to their patients and/or family members and neighbours. Common reasons for preferring self-sampling were less (anticipated) pain compared to speculum examination and more privacy. CONCLUSIONS: Self-sampling for cervical cancer screening is highly acceptable to female HCPs. Setting up a workplace screening program that entails the option of self-sampling could create greater awareness and positive attitudes among HCPs to educating their patients, families, and neighbours on cervical cancer risks and motivate HCPs to advocate for women's participation in screening.

Characterization of Human Papillomavirus prevalence and risk factors to guide cervical cancer screening in the North Tongu District, Ghana.

INTRODUCTION: This population-based study aimed to fill the knowledge gap on Human Papillomavirus (HPV) prevalence and associated sociodemographic risk factors of the general population in the North Tongu District, Ghana. These results are needed to guide cervical cancer prevention efforts, as the leading type of female cancers. METHODS: A cross-sectional study including 2002 women in the North Tongu District, Ghana investigated HPV prevalence and associated sociodemographic risk factors. Women were recruited by geographical distribution through the local community-based health system and samples collected using a self-sampling device. For HPV genotyping BSGP5+/6+-PCR with Luminex-MPG readout was used. Multivariate logistic regression analyzed sociodemographic risk factors for HPV positivity. RESULTS: Of 2002 self-collected samples, 1943 were eligible, contained sufficient DNA and provided valid HPV genotyping results. Prevalence of single high risk HPV types was 32.3% and of multiple high risk types 9.7%. The five most common detected HPV types were HPV16 (7.4%; 95%CI: 6.3-8.7), HPV52 (7.2%; 95%CI: 6.1-8.5), HPV35 (4.8%; 95%CI: 3.9-5.8), HPV59 (4.7%; 95%CI: 3.8-5.8), HPV56 (3.9%; 95%CI: 3.1-4.8). Highest prevalence was observed among women aged 18-24 years, while age 25-54 years was inversely associated with high risk HPV positivity in multivariate analysis. Sociodemographic risk factors identified were i) having any sexual partner, ii) more partners increased the odds for high risk HPV positivity, iii) independently from this marital status, in particular not being married. DISCUSSION & CONCLUSION: Most importantly, the high risk HPV prevalence detected from this study is higher than estimates reported for Western Africa. This needs be considered, when deciding on the cervical cancer screening algorithms introduced on a wider scale. Follow-up and triage, depending on the methods chosen, can easily overburden the health system. Self-sampling worked well and provided adequate samples for HPV-based screening. Women with increasing number of sexual partners and not being married were found to have higher odds of being high risk HPV positive, therefore could be a higher prioritized screening target group.

Dynamics of genotype-specific HPV clearance and reinfection in rural Ghana may compromise HPV screening approaches.

Persistent Human Papillomavirus (HPV) infection is a prerequisite for cervical cancer development. Few studies investigated clearance of high-risk HPV in low-and-middle-income countries. Our study investigated HPV clearance and persistence over four years in women from North Tongu District, Ghana. In 2010/2011, cervical swabs of 500 patients were collected and HPV genotyped (nested multiplex PCR) in Accra, Ghana. In 2014, 104 women who previously tested positive for high-risk HPV and remained untreated were re-tested for HPV. Cytobrush samples were genotyped (GP5+/6+ PCR & Luminex-MPG readout) in Berlin, Germany. Positively tested patients underwent colposcopy and treatment if indicated. Of 104 women, who tested high-risk HPV+ in 2010/2011, seven (6,7%; 95%CI: 2.7-13.4%) had ≥1 persistent high-risk-infection after ~4 years (mean age 39 years). Ninety-seven (93,3%; 95%CI: 86.6-97.3%) had cleared the original infection, while 22 (21.2%; 95%CI: 13.8-30.3%) had acquired new high-risk infections with other genotypes. Persistent types found were HPV 16, 18, 35, 39, 51, 52, 58, and 68. Among those patients, one case of CIN2 (HPV 68) and one micro-invasive cervical cancer (HPV 16) were detected. This longitudinal observational data suggest that single HPV screening rounds may lead to over-referral. Including type-specific HPV re-testing or additional triage methods could help reduce follow-up rates.

Marrow Adipose Tissue: Skeletal Location, Sexual Dimorphism, and Response to Sex Steroid Deficiency.

Marrow adipose tissue (MAT) is unique with respect to origin, metabolism, and function. MAT is characterized with high heterogeneity which correlates with skeletal location and bone metabolism. This fat depot is also highly sensitive to various hormonal, environmental, and pharmacologic cues to which it responds with changes in volume and/or metabolic phenotype. We have demonstrated previously that MAT has characteristics of both white (WAT) and brown (BAT)-like or beige adipose tissue, and that beige phenotype is attenuated with aging and in diabetes. Here, we extended our analysis by comparing MAT phenotype in different locations within a tibia bone of mature C57BL/6 mice and with respect to the presence of sex steroids in males and females. We report that MAT juxtaposed to trabecular bone of proximal tibia (pMAT) is characterized by elevated expression of beige fat markers including Ucp1, HoxC9, Prdm16, Tbx1, and Dio2, when compared with MAT located in distal tibia (dMAT). There is also a difference in tissue organization with adipocytes in proximal tibia being dispersed between trabeculae, while adipocytes in distal tibia being densely packed. Higher trabecular bone mass (BV/TV) in males correlates with lower pMAT volume and higher expression of beige markers in the same location, when compared with females. However, there is no sexual divergence in the volume and transcriptional profile of dMAT. A removal of ovaries in females resulted in decreased cortical bone mass and increased volume of both pMAT and dMAT, as well as volume of gonadal WAT (gWAT). Increase in pMAT volume was associated with marked increase in Fabp4 and Adiponectin expression and relative decrease in beige fat gene markers. A removal of testes in males resulted in cortical and trabecular bone loss and the tendency to increased volume of both pMAT and dMAT, despite a loss of gWAT. Orchiectomy did not affect the expression of white and beige adipocyte gene markers. In conclusion, expression profile of beige adipocyte gene markers correlates with skeletal location of active bone remodeling and higher BV/TV, however bone loss resulted from sex steroid deficiency is not proportional to MAT expansion at the same skeletal location.