Viviane Bremer

Understanding recent increases in the incidence of sexually transmitted infections in men having sex with men: changes in risk behavior from risk avoidance to risk reduction.

Objective: The objective of this study was to explore risk behavior and routes of transmission in men having sex with men (MSM) with newly diagnosed sexually transmitted infections (STIs). Methods: A questionnaire on clinical diagnosis and manifestation site for acute STIs was completed by physicians participating in a sentinel study. Patients contributed information on sexual risk behavior and the likely route of STI transmission. Results: Three hundred fifty-six diagnosis forms and 169 matching patient questionnaires could be analyzed. The most frequent diagnosis was syphilis (n = 147; 33% primary syphilis with ulcer localization 71% genital, 22% anorectal, and 8% oral; 67% secondary syphilis), followed by gonorrhea (n = 136; 59% genital, 34% rectal, 7% pharyngeal) and Chlamydia trachomatis infection (n = 51; 48% genital, 48% rectal, 4% pharyngeal). In 12 patients, more than one infection was diagnosed, and 2 or 3 sites were affected in 11 patients. Approximately 60% of infections were acquired by genital–oral and oral–anal practices. Unprotected anal intercourse (UAI) was reported more often by HIV-positive men (mostly receptive) and men with high partner numbers. Conclusion: High partner numbers, an important role of genital–oral sexual practices for the transmission of STIs, and relatively high frequencies of mostly receptive UAI in HIV-positive men are all contributing to increasing STI incidences among MSM.

Sexually transmitted infections and prostate cancer risk: A systematic review and meta-analysis

Prostate cancer (PC) is the second most incident cancer and the sixth cause of death by cancer in men worldwide. Despite extensive research efforts, no modifiable risk factors have been consistently identified for PC risk. A number of studies have focused on possible relationships between sexually transmitted infections (STIs) and PC. We performed a meta-analysis to explore the association between infection caused by Neisseria gonorrheae, Treponema pallidum, Chlamydia trachomatis, Trichomonas vaginalis, Ureaplasma urealyticum, Mycoplasma hominis, Herpes Simplex Virus types 1 and 2, Human Herpes Virus 8 and Cytomegalovirus, and PC. We conducted a comprehensive, systematic bibliographic search of medical literature to identify relevant studies. We calculated summary relative risk (SRR) and 95% confidence intervals (CI) for the association between each STI and PC through random effect models. Subgroup, meta-regression and sensitivity analyses were carried out to detect between-study heterogeneity and bias. We included 47 studies published between 1971 and 2011. Men who reported having ever had any STI in lifetime had an increased PC (SRR 1.49, 95% CI 1.19-1.92). We found a significantly increased PC risk in men having had gonorrhoea (SRR 1.20, 95% CI 1.05-1.37). No other single STI was significantly associated with PC. Due to high incidence of both STIs and PC worldwide, prevention of STIs may help preventing a considerable number of PC cases.

Syphilis surveillance and trends of the syphilis epidemic in Germany since the mid-90s.

Recent surveillance reports from Europe and the United States show an increase in syphilis cases. Accurate epidemiological information about the distribution of syphilis is important for targeting screening and intervention programmes. The German syphilis notification system changed in 2001 from physician to laboratory-based reporting, which is complemented by a newly introduced sexually transmitted infection (STI) sentinel system. After reaching an all time low during the 1990s, syphilis notifications have increased significantly since 2001, coinciding with the introduction of the new reporting system. However, the increased reported incidence is reflecting a true rise in the number of cases and is not predominantly determined by more underreporting through the previous reporting system. The increase reflects syphilis outbreaks among men who have sex with men (MSM). The first of these outbreaks was observed in Hamburg in 1997. In 2003, incidence in men was ten times higher than in women. An estimated 75% of syphilis cases are currently diagnosed among MSM. A high proportion (according to sentinel data, up to 50%) of MSM diagnosed with syphilis are HIV positive. The continuously high number of syphilis cases diagnosed among heterosexuals in Germany in recent years compared with other western European countries may reflect the higher population movement between Germany and syphilis high incidence regions in south-east and eastern Europe.

Relation between the HIV and the re-emerging syphilis epidemic among MSM in Germany: an analysis based on anonymous surveillance data

In 2003, for the first time since the introduction of highly active antiretroviral therapy (HAART), the number of newly diagnosed HIV infections in Germany increased considerably compared to the previous year. The increase was largely restricted to men who have sex with men (MSM) from larger cities. In this group the number of newly diagnosed HIV infections increased about 30% compared to 2002. Since the late 1990s syphilis infections among MSM also increased in Germany, concentrated in larger cities.

Viral hepatitis in Germany: poor vaccination coverage and little knowledge about transmission in target groups

BackgroundIn Germany, vaccination against hepatitis B is recommended for infants, children and adolescents since 1995 and for specific target groups since 1982. Little is known about knowledge about viral hepatitis and attitudes toward hepatitis B vaccination-factors likely to influence vaccine uptake.MethodsIn order to estimate vaccination coverage in adult target groups and in the overall adult population and to assess knowledge and attitudes, we conducted a nationwide cross-sectional telephone survey among 412 persons in November 2004. We defined participants as being vaccinated if they reported at least one previous vaccination against hepatitis B.ResultsVaccination coverage (vc) standardised for age, sex and residence was 29.6% in the general population and 58.2% in target groups for hepatitis B vaccination. Particular gaps in vaccine coverage were detected among health care workers (vc: 69.5%) and chronically ill persons (vc: 22.0%). Knowledge on risk factors and transmission was far below expectations, whereas the acceptance of vaccination in the majority of the population (79.0%) was good.ConclusionWe conclude that educational measures could lead to a higher vaccination uptake in adult target groups.

Lymphogranuloma venereum emerging in men who have sex with men in Germany

A resurgence of lymphogranuloma venereum (LGV) has been observed in several European countries. LGV is not a mandatorily notifiable disease in Germany. Reports of LGV cases have actively been collected by the Robert Koch-Institut since 2004 to describe the outbreak and estimate the extent of the LGV problem in Germany. Updates on the LGV outbreak were published in the German national epidemiological bulletin. Physicians were asked to send their samples to a laboratory for genotyping. A possible case was defined as a person with symptoms of proctitis and/or inguinal lymph node swelling and a positive chlamydia serology. A probable case had in addition a positive chlamydia rectal or urinary PCR test. A case was confirmed if the genotype L1-L3 was identified based on sequence analysis of omp1 gene sequences. Since 2003, LGV has been reported in 78 male patients in Germany. Of these, 61 patients were confirmed as genotype L2. Fifty eight out of 78 patients (74%) are known to be men who have sex with men (MSM). Fifty five patients (71%) had rectal symptoms and 49 (63%) knew they were HIV positive. Sixty two (79%) of the patients were residents of Berlin or Hamburg. LGV has emerged in MSM in Germany at the same time as in other European countries. It is thought that LGV may become endemic in the MSM community in German metropolitan areas, because the number of reported patients with LGV continues to increase. The increase in the number of LGV cases and the high HIV prevalence in LGV patients are of great public health concern. Clinicians and MSM may not be sufficiently aware of the disease, and existing efforts to promote awareness and prevention of sexually transmitted infections and HIV need to be strengthened.

Building a sentinel surveillance system for sexually transmitted infections in Germany, 2003

Background/objectives: Increases in STIs have been reported from the United States and Europe. Since 2001, only syphilis and HIV are notifiable in Germany. A sentinel surveillance system has been set up to assess the occurrence and trends of STIs and identify risk groups. Methods: Through the sentinel system data are collected from local health offices (LHO), hospital based STI clinics and private practitioners (dermato-venerology, urology, gynaecology, or HIV). For every newly diagnosed laboratory confirmed infection of HIV, gonorrhoea, chlamydia, syphilis, or trichomoniasis physicians complete a standardised questionnaire regarding diagnosis, source of infection, and demographic information. Patients complete a questionnaire about sexual risk behaviour. The patient form is matched with the diagnosis form using a unique identifier number. Characteristics of sentinel patients were compared with those reported through the HIV and syphilis national notification system. Results: 58 LHO, 14 hospital based STI clinics, and 160 private practitioners (53.1% dermato-venerologists) from all federal states participated in the study. 176 (75.9%) sentinel sites are located in cities of >100 000 inhabitants. From 1 March 2003–29 February 2004, a total of 1833 STIs have been reported, among them 452 chlamydia, 321 syphilis (10.9% of notified syphilis), 343 gonorrhoea, 269 HIV (15.7% of notified HIV). 925 (50.5%) of the patients were male, the median age was 31 years. Female patients were more often of foreign origin (χ2 test; 70.0% v 26.3%; p<0.001). Conclusions: Our sentinel system will provide a base for detection of STI trends in Germany. In addition, information about sexual risk behaviour will enable us to target prevention at those most at risk for STIs.

Increased incidence of syphilis in men who have sex with men and risk management strategies, Germany, 2015

In Germany, the number of reported syphilis cases increased between 11% and 22% per year between 2010 and 2014. We analysed syphilis surveillance data and data of four behavioural surveys on men who have sex with men (MSM) in Germany (2003, 2007, 2010, 2013) to assess if this rise is ongoing and to find possible explanations for it. Syphilis notifications increased in 2015 by 19% to a total of 6,834. This was mainly due to increasing notifications in MSM of all age groups in larger German cities. Data from the behavioural surveys on MSM in Germany showed a simultaneous increase of selective condom use as HIV-status-bases risk management strategy and the number of syphilis cases. MSM diagnosed with HIV reported condomless anal intercourse with non-steady partners more frequent than MSM not diagnosed with HIV or untested for HIV, but the latter also reported higher frequencies of this behaviour in the more recent surveys. Transmission in HIV-positive MSM probably plays an important, but not exclusive role, for the syphilis dynamics in Germany. A risk adapted routine screening for sexually active MSM and potentially innovative approaches to increase early screening and treatment of syphilis such as internet counselling, home sampling, home testing and broadening venue-based (rapid) testing, should be critically evaluated to effectively reduce syphilis infections.

Prevalence of Chlamydia trachomatis among young German adolescents, 2005-06.

BACKGROUND Chlamydia trachomatis prevalence among 12-17-year-old adolescents in Germany was determined in the present study. METHODS A random age-stratified sample of 1815 urine specimens of boys and girls was selected from a population-based nationwide health survey conducted in 2003-06. Urine samples were pooled and tested for chlamydia using strand displacement amplification. Positive pools were individually retested. Prevalence, prevalence ratios (PR) and corresponding 95% confidence intervals (CI) were calculated. Associations between infection and socio-demographic factors (age, sex, place of residence), sexual activity (defined by oral contraceptive use or gynaecologist visits) and abdominal pain among females were examined in univariate analysis. RESULTS Sixteen samples (0.9% 95% CI: 0.5-1.3%), all from 15-17-year olds, were positive for chlamydia. Prevalence increased with age to 2% (95% CI: 0.8-3.2%) among 17 year olds and was higher among girls than boys (1.8% v. 0.1%; P < 0.001). A total of 4.6% (95% CI: 1.4-7.7%) of sexually active girls aged 17 were infected and 5/7 of them had no regular abdominal pain. Of all girls with abdominal pains, 52% had visited gynaecologists. Prevalence of infection was higher among those with pains than those without (PR = 3.8, 95% CI: 1.3-11.0). CONCLUSIONS This is the first nationwide study based on a representative sample of boys and girls to measure chlamydia prevalence among adolescents in Germany. Prevalence in Germany is consistent with other countries. Among sexually active females, prevalence was comparable to screening thresholds. As gynaecological visits were common among females, we recommend that gynaecologists should actively offer screening to sexually active females, which would strengthen the newly implemented screening for females under 25 years.

Real-world treatment for chronic hepatitis C infection in Germany: Analyses from drug prescription data, 2010–2015

BACKGROUND & AIMS Direct-acting antivirals (DAAs) for hepatitis C virus (HCV) have strongly improved treatment options since 2014, but it is unclear if treatment numbers have increased. We aimed to estimate the number of treatment regimens per month from 2010-2015 and the number of patients treated and cured with DAAs since 2014, as well as the associated costs. METHODS Drug prescription data of hepatitis C virus (HCV) antivirals for patients with statutory health insurance in Germany (∼85% of population) from January 2010-December 2015 were evaluated. Standard 28-day prescriptions of pegylated interferon (PegIFN) and 1st/2nd generation DAAs were combined according to treatment guidelines and analysed. Drug costs were calculated from pharmacy sales prices. Mean treatment durations/regimen from real-world data were used to calculate drug costs/regimen and numbers of DAA-treated persons in 2014/15. RESULTS From January 2010-December 2015 PegIFN/ribavirin-treatments/month decreased from ∼6500 to ∼650. Monthly HCV-prescriptions rose with the approval of 1st generation DAAs (2011), and decreased at the end of 2013. With the approval of 2nd generation DAAs, prescriptions/month increased (peak: ∼6600; March 2015), and subsequently decreased (∼4000; December 2015). In 2014, ∼7000 patients were treated with DAAs, and ∼20,100 in 2015. Treatment costs/month were stable at 12 million EUR (2010-2011), increased to ∼38 million EUR (March 2012), and peaked to 150 million EUR (March 2015). DAA-drug costs/year added up to ∼664million EUR (2014) and ∼1.3billion EUR (2015). CONCLUSIONS Despite an increase in DAA prescriptions, in December 2015 less persons/month were under treatment compared to January 2010, even though access to DAAs is not limited. However, yearly treatment numbers increased from 2014-2015. Under observed conditions, ∼18,000 patients/year can be cured, making substantial reduction of the estimated 160,000 diagnosed patients realizable. Political commitment to achieve further reduce DAA-prices and increase treatment numbers is recommended. LAY SUMMARY New treatment options with all-oral second generation direct-acting antivirals (DAAs) have resulted in the potential to cure chronic hepatitis C infection, but at high costs. Analyses from HCV drug prescription data of patients with statutory health insurance in Germany from 2010-2015, showed that DAAs replaced treatments with pegylated interferon and ribavirin, but accompanied by a disproportionate rise in costs. Although the monthly number of patients under treatment did not increase over time, the total number of patients yearly treated with DAAs increased from ∼7000 patients in 2014 to ∼20,100 in 2015, with a trend to shorter treatment regimens. Under observed conditions ∼18,000 patients can be cured yearly, making a substantial reduction of the estimated 160,000 diagnosed patients in Germany achievable.