Klaus Jansen

Lymphogranuloma Venereum in Men Screened for Pharyngeal and Rectal Infection, Germany

To determine prevalence of lymphogranuloma venereum among men who have sex with men in Germany, we conducted a multicenter study during 2009–2010 and found high rates of rectal and pharyngeal infection in men positive for the causative agent, Chlamydia trachomatis. Many infections were asymptomatic. An adjusted C. trachomatis screening policy is justified in Germany.

High Prevalence and High Incidence of Coinfection with Hepatitis B, Hepatitis C, and Syphilis and Low Rate of Effective Vaccination against Hepatitis B in HIV-Positive Men Who Have Sex with Men with Known Date of HIV Seroconversion in Germany

Objectives Men who have sex with men (MSM) are at higher risk for coinfection with hepatitis B virus (HBV), hepatitis C virus (HCV), and syphilis than the general population. HIV infection and these coinfections accelerate disease progression reciprocally. This study evaluated the prevalence and incidence of these coinfections in HIV1-positive MSM in Germany. Materials and Methods As part of a nationwide, multicenter, prospective cohort study of HIV-infected MSM, plasma samples collected yearly were screened for HBsAg and antibodies to HBc, HBs, HCV, and syphilis. Samples with indications of active HBV or HCV infection were confirmed by polymerase chain reaction. Prevalence and incidence of each infection and incidence rates per study participant were calculated, and incidences over 4-year time intervals compared. Results This study screened 5,445 samples from 1,843 MSM. Median age at HIV seroconversion was 33 years. Prevalences of active, cleared, and occult HBV, and of active/cleared HCV were 1.7%, 27.1%, 0.2%, and 8.2%, respectively, and 47.5% had been effectively vaccinated against HBV. Prevalence of antibodies to Treponema pallidum and of triple or quadruple sexually transmitted infections (STIs) were 39.6% and 18.9%, respectively. Prevalence of STI, cleared HBV, HBV vaccination, and history of syphilis differed significantly among age groups. Incidences of HBV, HCV, and syphilis were 2.51, 1.54, and 4.06 per 100 person-years, respectively. Incidences of HCV and syphilis increased over time. HCV incidence was significantly higher in MSM coinfected with syphilis and living in Berlin, and syphilis incidence was significantly higher for MSM living in Berlin. Discussion Despite extensive HBV vaccination campaigns, fewer than 50% of screened MSM were effectively vaccinated, with a high proportion of HIV-positive MSM coinfected with HBV. High rates of STI coinfections in HIV-positive MSM and increasing incidences emphasize the need for better tailored campaigns for HBV vaccination and STI prevention.

First Line Treatment Response in Patients with Transmitted HIV Drug Resistance and Well Defined Time Point of HIV Infection: Updated Results from the German HIV-1 Seroconverter Study

Background Transmission of drug-resistant HIV-1 (TDR) can impair the virologic response to antiretroviral combination therapy. Aim of the study was to assess the impact of TDR on treatment success of resistance test-guided first-line therapy in the German HIV-1 Seroconverter Cohort for patients infected with HIV between 1996 and 2010. An update of the prevalence of TDR and trend over time was performed. Methods Data of 1,667 HIV-infected individuals who seroconverted between 1996 and 2010 were analysed. The WHO drug resistance mutations list was used to identify resistance-associated HIV mutations in drug-naïve patients for epidemiological analysis. For treatment success analysis the Stanford algorithm was used to classify a subset of 323 drug-naïve genotyped patients who received a first-line cART into three resistance groups: patients without TDR, patients with TDR and fully active cART and patients with TDR and non-fully active cART. The frequency of virologic failure 5 to 12 months after treatment initiation was determined. Results Prevalence of TDR was stable at a high mean level of 11.9% (198/1,667) in the HIV-1 Seroconverter Cohort without significant trend over time. Nucleotide reverse transcriptase inhibitor resistance was predominant (6.0%) and decreased significantly over time (OR = 0.92, CI = 0.87–0.98, p = 0.01). Non-nucleoside reverse transcriptase inhibitor (2.4%; OR = 1.00, CI = 0.92–1.09, p = 0.96) and protease inhibitor resistance (2.0%; OR = 0.94, CI = 0.861.03, p = 0.17) remained stable. Virologic failure was observed in 6.5% of patients with TDR receiving fully active cART, 5,6% of patients with TDR receiving non-fully active cART and 3.2% of patients without TDR. The difference between the three groups was not significant (p = 0.41). Conclusion Overall prevalence of TDR remained stable at a rather high level. No significant differences in the frequency of virologic failure were identified during first-line cART between patients with TDR and fully-active cART, patients with TDR and non-fully active cART and patients without TDR.

Improved testing of recent HIV-1 infections with the BioRad avidity assay compared to the limiting antigen avidity assay and BED Capture enzyme immunoassay: evaluation using reference sample panels from the German Seroconverter Cohort.

Background The variety and limitations of current laboratory methods for estimating HIV-incidence has driven attempts to improve and standardize the performance of serological ‘Tests for Recent HIV-Infections’ (TRI). Primary and follow-up HIV-1 positive plasma samples from individuals with well-defined dates of infection collected as part of the German Seroconverter Cohort provided specimens highly suitable for use in comparing the performance of three TRIs: the AWARE™ BED™ EIA HIV-1 Incidence test (BED-CEIA), Genetic systems HIV-1/HIV-2 Plus O EIA antibody avidity-based assay (BioRad Avidity) and Sedia™ HIV-1 LAg Avidity EIA (LAg Avidity). Methods The evaluation panel included 180 specimens: 44 from antiretroviral (ARV)-naïve individuals with recently acquired HIV-infection (≤130 days; 25 B and 19 non-B subtypes) and 136 from long-term (>12 months) infected individuals [101 ARV-naïve subtype B, 16 non-B subtypes, 14 ARV-treated individuals, 5 slow progressors (SLP)]. Results For long-term infected, ARV-naïve individuals the false recent rates (FRR) of both the BioRad and LAg Avidity assays were 2% (2/101 for subtype B) and 6% (1/16 for subtype ‘non-B’), while the FRR of the BED-CEIA was 7% (7/101 for subtype B) and 25% (4/16 for subtype ‘non-B’) (all p>0.05). Misclassification of ARV-treated individuals and SLP was rare by LAg (1/14, 0/5) and BioRad Avidity assays (2/14, 1/5) but more frequent by BED-CEIA (5/14, 3/5). Among recently-infected individuals (subtype B), 60% (15/25) were correctly classified by BED-CEIA, 88% (22/25) by BioRad Avidity and significantly fewer by LAg (48%, 12/25) compared to BioRad Avidity (p = 0.005) with a higher true-recency rate among non-B infections for all assays. Conclusions This study using well-characterized specimens demonstrated lower FRRs for both avidity methods than with the BED-CEIA. For recently infected individuals the BioRad Avidity assay was shown to give the most accurate results.

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.

Influence of Major HIV-1 Protease Inhibitor Resistance Mutations on CTL Recognition

Background:HIV-1 protease is subjected to dual selection pressure exerted by protease inhibitors (PIs) and cytotoxic T lymphocytes (CTL). Recently, we identified KMIGGIGGF (KF9) as a HLA-B*1501-restricted CTL epitope, including several major PI resistance mutations (M46I/L, I47A/V, G48V, I50V). To assess potential interactions between KF9-specific CTL and emergence of these important resistance mutations, we studied CTL recognition of the mutations and analyzed protease sequences in an HLA-I-typed patient cohort. Methods:CTL recognition of KF9 and resistance mutations in KF9 were studied in 38 HLA-B*1501-positive HIV-1-infected patients using variant KF9 peptides in interferon-γ enzyme-linked immunospot assays. Protease sequences were analyzed in 302 HLA-I-typed HIV-1-infected patients. Results:G48V abolished KF9 recognition by CTL in all patients. Furthermore, M46I, I47A, and I50V could impair or abolish CTL recognition in many patients. In contrast, M46L and I47V showed good CTL recognition in nearly all patients. HIV-1 protease sequence analysis showed no statistical correlation between the occurrence of resistance mutations in KF9 and HLA-B*1501. Viral load in patients failing therapy with KF9 mutations was significantly lower in HLA-B*1501-positive patients in comparison with HLA-B*1501-negative patients. Conclusions:PI mutations, G48V, M46I, and I47A, can abrogate CTL recognition, indicating potential interactions between development of drug resistance and CTL response. However, we could not find evidence that development of these PI mutations is influenced by KF9-specific CTL.

Migrationshintergrund in der infektionsepidemiologischen Surveillance in Deutschland

ZusammenfassungHintergrundMigration beeinflusst die Epidemiologie von Infektionskrankheiten. Sich daraus ergebende Risikogruppen und Präventionsbedarfe zu identifizieren, ist Grundlage für eine adäquate Gestaltung von Public-Health-Maßnahmen. Es stellt sich die Frage, inwieweit sich migrationsspezifische Informationen hierfür direkt aus der infektionsepidemiologischen Surveillance ableiten lassen.Ziel der ArbeitZiel ist eine systematische Darstellung von Indikatoren zur Operationalisierung des Migrationshintergrundes in der infektionsepidemiologischen Surveillance in Deutschland sowie die Einschätzung bestehender Einschränkungen.MethodikFür meldepflichtige Krankheiten bzw. Erregernachweise werden die jeweils erhobenen Indikatoren für Migration und deren Grundlage im Infektionsschutzgesetz dargestellt. Für Tuberkulose (TB), HIV und Syphilis werden Meldedaten für 2002–2013 deskriptiv analysiert.ErgebnisseBei fünf Infektionskrankheiten wurden – unterschiedlich operationalisiert – Informationen zum Migrationshintergrund erhoben. Bei TB (Geburtsland) und HIV (Herkunftsland) war eine nicht-deutsche Herkunft deutlich häufiger als bei Syphilis (Herkunftsland) mit 46, 30 bzw. 13 % der Fälle mit entsprechenden Angaben. Bei allen drei betrachteten Infektionskrankheiten ergaben sich Hinweise auf migrationsspezifische Risikoprofile.DiskussionEinheitliche Indikatoren für Migration in der infektionsepidemiologischen Surveillance würden die internationale und erregerübergreifende Vergleichbarkeit der Daten ermöglichen. Die Surveillance erlaubt aktuell teilweise migrationssensible Analysen, jedoch bedarf es zusätzlicher Studien, um die komplexen Zusammenhänge von Migration und Infektionskrankheiten richtig interpretieren und Public-Health-Maßnahmen bedarfsgerecht gestalten zu können.AbstractBackgroundMigration is an important factor impacting on infectious disease epidemiology. The timely identification of groups at risk and prevention needs resulting from migration is indispensable to adequately design and implement public health measures. It remains to be assessed to which extent surveillance data for notifiable diseases can directly generate meaningful migration-specific information.ObjectivesThe objectives of this study are to review indicators of migration background utilized in the German infectious disease surveillance, as well as to assess their limitations.MethodsWe describe the indicators of migration used for mandatorily notifiable diseases and pathogens and their legal basis in the Protection against Infection Act and conduct a descriptive analysis of surveillance data for tuberculosis (TB), HIV and syphilis from 2002–2013.ResultsMigration status is collected only for five infectious diseases and operationalization varies. For TB (country of birth) and HIV (country of origin) a foreign origin was more frequent than for syphilis (country of origin); namely 46, 30 and 13 % of cases with available information, respectively. In all three examples, there are indications of risk profiles that are specific for particular groups of migrants.DiscussionA standardization of indicators of migration in infectious disease surveillance is important to enhance data comparability between diseases and pathogens as well as across countries. Routine surveillance already partly allows migration sensitive analyses, yet further research is needed to guide interpretation of the complex relationship between migration and infectious diseases and plan public health measures adequately.BACKGROUND Migration is an important factor impacting on infectious disease epidemiology. The timely identification of groups at risk and prevention needs resulting from migration is indispensable to adequately design and implement public health measures. It remains to be assessed to which extent surveillance data for notifiable diseases can directly generate meaningful migration-specific information. OBJECTIVES The objectives of this study are to review indicators of migration background utilized in the German infectious disease surveillance, as well as to assess their limitations. METHODS We describe the indicators of migration used for mandatorily notifiable diseases and pathogens and their legal basis in the Protection against Infection Act and conduct a descriptive analysis of surveillance data for tuberculosis (TB), HIV and syphilis from 2002-2013. RESULTS Migration status is collected only for five infectious diseases and operationalization varies. For TB (country of birth) and HIV (country of origin) a foreign origin was more frequent than for syphilis (country of origin); namely 46, 30 and 13% of cases with available information, respectively. In all three examples, there are indications of risk profiles that are specific for particular groups of migrants. DISCUSSION A standardization of indicators of migration in infectious disease surveillance is important to enhance data comparability between diseases and pathogens as well as across countries. Routine surveillance already partly allows migration sensitive analyses, yet further research is needed to guide interpretation of the complex relationship between migration and infectious diseases and plan public health measures adequately.

[Migration and infectious disease surveillance in Germany: Analyses of Tuberculosis, HIV and Syphilis surveillance data].

ZusammenfassungHintergrundMigration beeinflusst die Epidemiologie von Infektionskrankheiten. Sich daraus ergebende Risikogruppen und Präventionsbedarfe zu identifizieren, ist Grundlage für eine adäquate Gestaltung von Public-Health-Maßnahmen. Es stellt sich die Frage, inwieweit sich migrationsspezifische Informationen hierfür direkt aus der infektionsepidemiologischen Surveillance ableiten lassen.Ziel der ArbeitZiel ist eine systematische Darstellung von Indikatoren zur Operationalisierung des Migrationshintergrundes in der infektionsepidemiologischen Surveillance in Deutschland sowie die Einschätzung bestehender Einschränkungen.MethodikFür meldepflichtige Krankheiten bzw. Erregernachweise werden die jeweils erhobenen Indikatoren für Migration und deren Grundlage im Infektionsschutzgesetz dargestellt. Für Tuberkulose (TB), HIV und Syphilis werden Meldedaten für 2002–2013 deskriptiv analysiert.ErgebnisseBei fünf Infektionskrankheiten wurden – unterschiedlich operationalisiert – Informationen zum Migrationshintergrund erhoben. Bei TB (Geburtsland) und HIV (Herkunftsland) war eine nicht-deutsche Herkunft deutlich häufiger als bei Syphilis (Herkunftsland) mit 46, 30 bzw. 13 % der Fälle mit entsprechenden Angaben. Bei allen drei betrachteten Infektionskrankheiten ergaben sich Hinweise auf migrationsspezifische Risikoprofile.DiskussionEinheitliche Indikatoren für Migration in der infektionsepidemiologischen Surveillance würden die internationale und erregerübergreifende Vergleichbarkeit der Daten ermöglichen. Die Surveillance erlaubt aktuell teilweise migrationssensible Analysen, jedoch bedarf es zusätzlicher Studien, um die komplexen Zusammenhänge von Migration und Infektionskrankheiten richtig interpretieren und Public-Health-Maßnahmen bedarfsgerecht gestalten zu können.AbstractBackgroundMigration is an important factor impacting on infectious disease epidemiology. The timely identification of groups at risk and prevention needs resulting from migration is indispensable to adequately design and implement public health measures. It remains to be assessed to which extent surveillance data for notifiable diseases can directly generate meaningful migration-specific information.ObjectivesThe objectives of this study are to review indicators of migration background utilized in the German infectious disease surveillance, as well as to assess their limitations.MethodsWe describe the indicators of migration used for mandatorily notifiable diseases and pathogens and their legal basis in the Protection against Infection Act and conduct a descriptive analysis of surveillance data for tuberculosis (TB), HIV and syphilis from 2002–2013.ResultsMigration status is collected only for five infectious diseases and operationalization varies. For TB (country of birth) and HIV (country of origin) a foreign origin was more frequent than for syphilis (country of origin); namely 46, 30 and 13 % of cases with available information, respectively. In all three examples, there are indications of risk profiles that are specific for particular groups of migrants.DiscussionA standardization of indicators of migration in infectious disease surveillance is important to enhance data comparability between diseases and pathogens as well as across countries. Routine surveillance already partly allows migration sensitive analyses, yet further research is needed to guide interpretation of the complex relationship between migration and infectious diseases and plan public health measures adequately.BACKGROUND Migration is an important factor impacting on infectious disease epidemiology. The timely identification of groups at risk and prevention needs resulting from migration is indispensable to adequately design and implement public health measures. It remains to be assessed to which extent surveillance data for notifiable diseases can directly generate meaningful migration-specific information. OBJECTIVES The objectives of this study are to review indicators of migration background utilized in the German infectious disease surveillance, as well as to assess their limitations. METHODS We describe the indicators of migration used for mandatorily notifiable diseases and pathogens and their legal basis in the Protection against Infection Act and conduct a descriptive analysis of surveillance data for tuberculosis (TB), HIV and syphilis from 2002-2013. RESULTS Migration status is collected only for five infectious diseases and operationalization varies. For TB (country of birth) and HIV (country of origin) a foreign origin was more frequent than for syphilis (country of origin); namely 46, 30 and 13% of cases with available information, respectively. In all three examples, there are indications of risk profiles that are specific for particular groups of migrants. DISCUSSION A standardization of indicators of migration in infectious disease surveillance is important to enhance data comparability between diseases and pathogens as well as across countries. Routine surveillance already partly allows migration sensitive analyses, yet further research is needed to guide interpretation of the complex relationship between migration and infectious diseases and plan public health measures adequately.

Decreasing seroprevalence of herpes simplex virus type 1 and type 2 in Germany leaves many people susceptible to genital infection: time to raise awareness and enhance control

BackgroundHerpes simplex infections (HSV1/2) are characterized by recurrent symptoms, a risk of neonatal herpes, and the facilitation of HIV transmission. In Germany, HSV1/2 infections are not notifiable and data are scarce. A previous study found higher HSV1/2 seroprevalences in women in East Germany than in women in West Germany. We assessed changes in the HSV1/2 seroprevalences over time and investigated determinants associated with HSV1/2 seropositivity to guide prevention and control.MethodsThe study was based on the German Health Interview and Examination Survey for Adults (DEGS; 2008–2011) and the German National Health Interview and Examination Survey (GNHIES; 1997–1999). We tested serum samples from DEGS participants for HSV1 and HSV2 immunoglobulin G. We used Pearson’s χ2 test to compare the HSV1/HSV2 seroprevalences in terms of sex, age, and region of residence (East/West Germany) and investigated potential determinants by calculating prevalence ratios (PR) with log-binomial regression. All statistical analyses included survey weights.ResultsIn total, 6627 DEGS participants were tested for HSV1, and 5013 were also tested for HSV2. Overall, HSV1 seroprevalence decreased significantly from 1997–1999 (82.1%; 95%CI 80.6–83.6) to 2008–2011 (78.4%; 95%CI 77.8–79.7). In the same period, overall HSV2 seroprevalence decreased significantly from 13.3% (95%CI 11.9–14.9) to 9.6% (95%CI 8.6–10.8), notably in 18–24-year-old men (10.4 to 0%) in East Germany. Women were more likely than men to be seropositive for HSV1 (PR 1.1) or HSV2 (PR 1.6). A lower level of education, smoking, and not speaking German were associated with HSV1 in both sexes. Women of older age, who smoked, or had a history of abortion and men of older age or who had not attended a nursery school during childhood were more often seropositive for HSV2.ConclusionThe reduced seroprevalences of HSV1 and HSV2 leave more people susceptible to genital HSV1/2 infections. Practitioners should be aware of HSV infection as a differential diagnosis for genital ulcers. We recommend educational interventions to raise awareness of the sexual transmission route of HSV1/2, possible consequences, and prevention. Interventions should especially target pregnant women, their partners, and people at risk of HIV.

Establishment of a voluntary electronic Chlamydia trachomatis laboratory surveillance system in Germany, 2008 to 2014

Chlamydia trachomatis (CT) infections are not reportable in Germany and limited data on prevalence are available. CT screening has been offered free of charge to pregnant women since 1995 and to all women under 25 years since 2008. For symptomatic women and men, diagnostic testing is covered by statutory health insurance. We describe the establishment of a nationwide, laboratory-based, voluntary sentinel that electronically collects information on all performed CT tests with test results, test reason and patient information. The sentinel represents one third of all performed CT tests in Germany. In the period from 2008 to 2014, 3,877,588 CT tests were reported, 93% in women. Women aged 20–24 years and men aged 25–29 years were the most frequently tested age groups. The overall proportion of positive tests (PPT) among women was 3.9% and among men 11.0%. The highest PPT among women was in the age groups 15–19 (6.8%) and 20–24 years (5.9%), and among men in the age groups 20–24 (19.2%), 15–19 (15.4%) and 25–29 years (14.8%). The PPT for CT was high among women and men younger than 25 years. Prevention is urgently needed. Monitoring of CT infection in Germany should be continued.