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We monitored antimicrobial susceptibility developments of Neisseria gonorrhoeae in Germany from January 2014 to May 2021. The proportion of isolates with azithromycin minimum inhibitory concentrations above the epidemiological cut-off increased substantially, from 1.3% in 2014 to 12.2% in 2020. Preliminary data from 2021 showed a further rise (January to May: 20.7%). Therefore, azithromycin as part of the recommended dual therapy in Germany for non-adherent patients is challenged. Antimicrobial susceptibility testing in clinical practice is crucial and continuous susceptibility surveillance indispensable.

Background Azithromycin resistant Neisseria gonorrhoeae (NG) isolates increased from 4.3% in 2016 to 9.2% in 2018 within the German Gonococcal Resistance Network (GORENET) NG sample collection. Using whole genome sequencing (WGS) of NG isolates in combination with clinical and epidemiological data, we aim to understand this observed increase. Methods GORENET was set up in 2013 as a laboratory network to monitor NG infections in Germany by collection of NG isolates, epidemiological and clinical data. In 2018, isolates with reduced susceptibility to azithromycin (MIC ≥ 0.25 mg/L) were analyzed by WGS followed by assignment of sequence types based on NG multiantigen sequence typing (NG-MAST) and multilocus sequence typing (MLST), detection of antimicrobial resistance determinants and generation of a core SNP distance-based neighbor-joining phylogenetic tree. Comparison with published isolates was performed based on a custom ad-hoc cgMLST scheme and calculation of a minimum spanning tree. Results Whole genome phylogenetic analyses resulted in 4 major clades corresponding to NG-MAST genogroups G2400, G3779 (G1407), G5441 and G12302. The clade comprising G12302 accounted for the majority of isolates with azithromycin resistance (MIC > 0.5 mg/L) and was characterized by the presence of the recently described Neisseria lactamica-like mosaic mtr locus. In addition, strains in this clade were significantly associated with rectal infection site and younger age. Comparison with published isolates revealed similarity between a US and a German isolate of MLST ST9363 (12 nucleotides difference) and between a US and a German isolate of MLST ST11422 (21 nucleotides difference). Conclusion Our data indicate the recently observed increase in isolates resistant to azithromycin in Germany coincides with clonal expansion of NG-MAST genogroup G12302 and suggest that, together with horizontal gene transfer of resistance determinants and well-established point mutations, international spread of resistant lineages plays a major role regarding azithromycin resistance in Germany.

We consider two related scheduling problems: single resource-constrained scheduling on identical parallel machines and a generalization with resource-dependent processing times. In both problems, jobs require a certain amount of an additional resource and have to be scheduled on machines minimizing the makespan, while at every point in time a given resource capacity is not exceeded. In the first variant of the problem, the processing times and resource amounts are fixed, while in the second the former depends on the latter. Both problems contain bin packing with cardinality constraint as a special case, and, therefore, these problems are strongly NP-complete even for a constant number of machines larger than three, which can be proven by a reduction from 3-Partition. Furthermore, if the number of machines is part of the input, then we cannot hope for an approximation algorithm with absolute approximation ratio smaller than 3/2. We present asymptotic fully polynomial time approximation schemes (AFPTAS) for the problems: For any ε > 0, a schedule of length at most (1+ε) times the optimum plus an additive term of O ( p max log (1/ε)/ε) is provided, and the running time is polynomially bounded in 1/ε and the input length. Up to now, only approximation algorithms with absolute approximation ratios were known. Furthermore, the AFPTAS for resource-constrained scheduling on identical parallel machines directly improves the additive term of the best AFPTAS for bin packing with cardinality constraint so far.

We study the Parallel Task Scheduling problem $Pm|size_j|C_{\max}$ with a constant number of machines. This problem is known to be strongly NP-complete for each $m \geq 5$, while it is solvable in pseudo-polynomial time for each $m \leq 3$. We give a positive answer to the long-standing open question whether this problem is strongly $NP$-complete for $m=4$. As a second result, we improve the lower bound of $\frac{12}{11}$ for approximating pseudo-polynomial Strip Packing to $\frac{5}{4}$. Since the best known approximation algorithm for this problem has a ratio of $\frac{4}{3} + \varepsilon$, this result narrows the gap between approximation ratio and inapproximability result by a significant step. Both results are proven by a reduction from the strongly $NP$-complete problem 3-Partition.

BackgroundPersistence of individuals at risk of HIV with Pre-Exposure Prophylaxis (PrEP) is critical for its impact on the HIV epidemic. We analysed factors associated with stopping PrEP, barriers that may deter people from continuing PrEP and investigated sexual behaviour after stopping PrEP.MethodsCurrent and former PrEP users in Germany were recruited to complete an anonymous online survey on PrEP use and sexual behaviour. Participants were recruited through dating apps, a PrEP community website, anonymous testing sites and peers. The results were analysed using descriptive methods and logistic regression.ResultsWe recruited 4848 current and 609 former PrEP users in two study waves (July–October 2018, April–June 2019). Former PrEP users were more likely 18–29 years old than current users (adjusted OR = 1.6, 95% confidence interval (CI) 1.1–2.3). Moreover, they were more often unhappy with their sex life, which was more pronounced in former daily PrEP users (aOR = 4.5, 95% CI 2.9–7.1) compared to former on-demand users (aOR = 1.8, 95% CI 1.1–2.9, pinteraction = 0.005). The most common reason for stopping PrEP was a reduced need for PrEP (49.1%). However, 31.4% of former users identified logistic reasons and 17.5% stopped due to side effects. Former PrEP users using PrEP p = 0.015) and not wanting to take a chemical substance (33.2% vs. 24.0%,p = 0.020) compared to former PrEP users who used PrEP for longer. After stopping PrEP, 18.7% of former PrEP users indicated inconsistent condom use while having ≥4 sex partners within the previous 6 months. Former PrEP users with many partners and inconsistent condom use more often indicated logistic reasons for stopping (46.5% vs. 27.9%,p ConclusionsTo maximise persistence with PrEP we need to develop strategies for younger PrEP users, reduce logistic barriers to access PrEP, and to develop effective communication on side-effect management. Moreover, prevention strategies for people stopping PrEP are required, since some remain at high risk for HIV.

We consider Integer Linear Programs (ILPs), where each variable corresponds to an integral point within a polytope \(\mathcal {P}\subseteq \mathbb {R}^{d}\), i. e., ILPs of the form \(\min \{c^{\top }x\mid \sum _{p\in \mathcal {P}\cap \mathbb {Z}^d} x_p p = b, x\in \mathbb {Z}^{|\mathcal {P}\cap \mathbb {Z}^d|}_{\ge 0}\}\). The distance between an optimal fractional solution and an optimal integral solution (called the proximity) is an important measure. A classical result by Cook et al. (Math. Program., 1986) shows that it is at most \(\varDelta ^{\varTheta (d)}\) where \(\varDelta =\Vert \mathcal {P}\cap \mathbb {Z}^{d} \Vert _{\infty }\) is the largest coefficient in the constraint matrix. Another important measure studies the change in an optimal solution if the right-hand side b is replaced by another right-hand side \(b'\). The distance between an optimal solution x w.r.t. b and an optimal solution \(x'\) w.r.t. \(b'\) (called the sensitivity) is similarly bounded, i. e., \(\Vert b-b' \Vert _{1}\cdot \varDelta ^{\varTheta (d)}\), also shown by Cook et al. (Math. Program., 1986).

Semi-online algorithms that are allowed to perform a bounded amount of repacking achieve guaranteed good worst-case behaviour in a more realistic setting. Most of the previous works focused on minimization problems that aim to minimize some costs. In this work, we study maximization problems that aim to maximize their profit.

Background HIV and hepatitis C virus (HCV) have shared routes of transmission among men who have sex with men (MSM). Routine testing facilitates early diagnosis and treatment, thereby preventing morbidity and onward transmission. We evaluated factors associated with HIV and HCV testing in a behaviorally vulnerable cohort of predominantly MSM. Methods From June 2018 through June 2019, the BRAHMS study enrolled adults at ten German outpatient clinics that serve gender and sexual minority populations. Participants completed behavioral questionnaires that captured prior experience with HIV and HCV testing. Multivariable robust Poisson regression was used to evaluate factors potentially associated with testing in the previous 6 months. Results Among 1017 participants with median age 33 (interquartile range 28–39) years, 1001 (98.4%) reported any lifetime history of HIV testing and 787 (77.4%) reported any HCV testing, including 16 (1.6%) known to be living with HCV. Testing within the last 6 months was reported by 921 (90.6%) and 513 (50.4%) for HIV and HCV, respectively. Recent HIV testing was more common among participants with higher education level and recent HCV testing. Recent HCV testing was more common among participants with non-cisgender identity, lifetime history of illicit drug use, hepatitis B immunity or infection, and recent HIV testing. Conclusion Prior testing for HIV was common in this cohort, but interventions are needed to improve HCV risk stratification and access to testing. HIV testing infrastructure can be successfully leveraged to support HCV testing, but differentiated preventive care delivery is needed for some vulnerable populations.

This paper considers parallel machine scheduling with incompatibilities between jobs. The jobs form a graph equivalent to a collection of disjoint cliques. No two jobs in a clique are allowed to be assigned to the same machine. Scheduling with incompatibilities between jobs represents a well-established line of research in scheduling theory and the case of disjoint cliques has received increasing attention in recent years. While the research up to this point has been focused on the makespan objective, we broaden the scope and study the classical total completion time criterion. In the setting without incompatibilities, this objective is well-known to admit polynomial time algorithms even for unrelated machines via matching techniques. We show that the introduction of incompatibility cliques results in a richer, more interesting picture. We prove that scheduling on identical machines remains solvable in polynomial time, while scheduling on unrelated machines becomes APX-hard. Next, we study the problem under the paradigm of fixed-parameter tractable algorithms (FPT). In particular, we consider a problem variant with assignment restrictions for the cliques rather than the jobs. We prove that, despite still being APX-hard, it can be solved in FPT time with respect to the number of cliques. Moreover, we show that the problem on unrelated machines can be solved in FPT time for reasonable parameters, in particular, the parameter combination: maximum processing time, number of job kinds, and number of machines or maximum processing time, number of job kinds, and number of cliques. The latter results are extensions of known results for the case without incompatibilities, and can even be further extended to the case of total weighted completion time. All of the FPT results make use of n-fold Integer Programs that recently received great attention by proving their usefulness for scheduling problems.

Within the German Gonococcal Resistance Network’s (GORENET) Neisseria gonorrhoeae (NG) sample collection, azithromycin-resistant NG isolates increased from 4.3% in 2016 to 9.2% in 2018. We aim to understand this observed increase using whole genome sequencing of NG isolates combined with epidemiological and clinical data. Reduced susceptibility to azithromycin in 2018 was predominately clonal (NG multiantigen sequence typing G12302) and could mainly be attributed to the recently described mosaic-like mtr locus. Our data suggest that, together with horizontal gene transfer of resistance determinants and well-established point mutations, international spread of resistant lineages plays a major role regarding azithromycin resistance in Germany.

Background Emerging antimicrobial resistance (AMR) challenges gonorrhoea treatment and requires surveillance. Aim This observational study describes the genetic diversity of Neisseria gonorrhoeae isolates in Germany from 2014 to 2017 and identifies N. gonorrhoeae multi-antigen sequence typing (NG-MAST) genogroups associated with AMR or some patient demographics. Methods 1,220 gonococcal isolates underwent AMR testing and NG-MAST. Associations between genogroups and AMR or sex/age of patients were statistically assessed. Results Patients’ median age was 32 years (interquartile range: 25–44); 1,078 isolates (88.4%) originated from men. In total, 432 NG-MAST sequence types including 156 novel ones were identified, resulting in 17 major genogroups covering 59.1% (721/1,220) of all isolates. Genogroups G1407 and G10557 (G7072) were significantly associated with decreased susceptibility to cefixime (Kruskal–Wallis chi-squared: 549.3442, df: 16, p

In February 2019, the fourth expert meeting on rapid diagnostic tests (RDTs) for sexually transmitted infections (STI) was held at the Robert Koch Institute (RKI) in Berlin. Novel technical developments and new aspects of RDT applications were discussed by representatives from the German STI Society (DSTIG); RKI; the Paul Ehrlich Institute; national reference centers for HIV, HBV, and HCV; and reference laboratories for Chlamydia, gonococci, and Treponema pallidum.As a result of this meeting, we present a revision of the joint statement on STI diagnostics with RDTs from 2017. The Regulation (EU) 2017/746 of the European Parliament and of the Council on in vitro diagnostic medical devices became effective in May 2017 and includes more stringent regulatory requirements for RDTs, mainly concerning conformity of manufacturing processes and performance characteristics of class D in vitro diagnostics (detection of HIV, HBV, HCV, and T. pallidum). Some RDTs for HIV, HCV, and T. pallidum have been evaluated in clinical studies and/or were WHO prequalified and may be used in low-threshold services. Among them are some HIV RDTs available and approved for self-testing. In addition, some HBV RDTs based on detection of HBs antigen (HBsAg) received WHO prequalification. However, false negative results may occur in samples with low HBsAg levels, as for instance in HIV-coinfected patients receiving antiretroviral therapy. For Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG), antigen-based RDTs still do not allow reliable detection of infection. Only PCR-based CT/NG RDTs possess sufficient diagnostic accuracy to be used as point-of-care tests. Rapid PCR tests for NG, however, do not provide any information about antimicrobial resistance.

Infections during pregnancy are one of the leading causes of increased morbidity and mortality in mothers and their newborns worldwide. In Germany, there has been standardized healthcare for pregnancy for more than 50 years. The maternity guidelines of the Joint Federal Committee form the legal framework for this and include the screening of pregnant women for HIV, syphilis, and hepatitis B, among other things.The aim of this work is to determine the extent to which screening is covered by the German population.With the help of anonymized routine data of legally insured persons available to the Institut für angewandte Gesundheitsforschung Berlin GmbH (InGef) from 2011 to 2015, a definition of pregnancy was developed with the use of various ICD-10 and EBM codes and the first evaluation of the use of tests for infectious agents in pregnancy was carried out.The high proportion of women who are tested for syphilis (95.3%) and hepatitis B (91.6%) during pregnancy indicates very good accessibility and use of prenatal screening services. For HIV, the proportion of women tested is significantly lower (84.9%).Whether pregnant women refuse an HIV test, the test was performed elsewhere, or not recommended by the medical staff cannot be clarified on the basis of the available data. In view of the highly effective medical intervention options for syphilis, HIV, and hepatitis B, the aim should be to test pregnant women in Germany as completely as possible. The reasons for the lack of screening must be further investigated and starting points for increasing the use must be identified.

Zusammenfassung Hintergrund Infektionen in der Schwangerschaft sind weltweit eine der führenden Ursachen für erhöhte Morbidität und Mortalität bei Müttern und ihren Neugeborenen. In Deutschland gibt es seit mehr als 50 Jahren eine standardisierte Gesundheitsvorsorge in der Schwangerschaft. Die Mutterschafts-Richtlinien des Gemeinsamen Bundesausschusses bilden hierzu den gesetzlichen Rahmen und umfassen unter anderem das Screening von Schwangeren auf HIV, Syphilis und Hepatitis B. Ziel der Arbeit Im Rahmen dieser Arbeit soll eruiert werden, wie hoch die Abdeckung des Screenings in der deutschen Bevölkerung ist. Material und Methoden Mithilfe von anonymisierten Routinedaten von gesetzlich Versicherten, die dem Institut für angewandte Gesundheitsforschung Berlin GmbH (InGef) aus den Jahren 2011 bis 2015 vorliegen, wurde mithilfe von verschiedenen Internationale statistische Klassifikationsziffern der Krankheiten und verwandter Gesundheitsprobleme(ICD-10)- und Einheitlicher Bewertungsmaßstab(EBM)-Ziffern eine Definition für Schwangerschaft entwickelt und eine erste Auswertung zur Inanspruchnahme von Testungen auf Infektionserreger in der Schwangerschaft vorgenommen. Ergebnisse Der hohe Anteil von Frauen, die im Rahmen der Schwangerschaft auf Syphilis (95,3 %) und Hepatitis B (91,6 %) getestet werden, spricht für eine sehr gute Erreichbarkeit und Inanspruchnahme von vorgeburtlichen Screeningangeboten. Bei HIV ist der Anteil an getesteten Frauen deutlich niedriger (84,9 %). Diskussion Ob Schwangere einen HIV-Test ablehnen, der Test anderweitig durchgeführt oder nicht durch das ärztliche Personal empfohlen wurde, lässt sich anhand der vorliegenden Datenlage nicht klären. Angesichts der hochwirksamen medizinischen Interventionsmöglichkeiten für Syphilis, HIV und Hepatitis B ist eine möglichst vollständige Testung von Schwangeren in Deutschland anzustreben. Die Gründe für fehlende Screeninguntersuchungen müssen weiter eruiert und Ansatzpunkte für eine Steigerung der Inanspruchnahme identifiziert werden.

Background Men who have sex with men (MSM) are disproportionally affected by sexually transmitted infections (STI). STI are often extragenital and asymptomatic. Both can delay diagnosis and treatment. Approval of HIV pre-exposure prophylaxis (PrEP) might have influenced sexual behaviour and STI-prevalence of HIV- MSM. We estimated STI-prevalence and risk factors amongst HIV- and HIV+ MSM in Germany to plan effective interventions. Methods We conducted a nationwide, cross-sectional study between February and July 2018. Thirteen MSM-friendly STI-practices screened MSM for Chlamydia trachomatis (CT), Mycoplasma genitalium (MG), Neisseria gonorrhea (NG), and Trichomonas vaginalis (TV) using self-collected rectal and pharyngeal swabs, and urine samples. APTIMA™ STI-assays (Hologic™ Inc., San Diego, USA) were used for diagnostics, and samples were not pooled. We collected information on socio-demographics, HIV-status, clinical symptoms, sexual behaviour within the last 6 months, and PrEP use. We combined HIV status and PrEP use for defining risk groups, and used directed acyclic graphs and multivariable logistic regression to identify risk factors for STI. Results Two thousand three hundred three MSM were included: 50.5% HIV+, median age 39 [18–79] years. Median number of male sex partners within the last 6 months was five. Sex without condom was reported by 73.6%, use of party drugs by 44.6%. 80.3% had a STI history, 32.2% of STI+ MSM reported STI-related symptoms. 27.6% of HIV- MSM used PrEP. Overall STI-prevalence was 30.1, 25.0% in HIV−/PrEP- MSM (CT:7.2%; MG:14.2%; NG:7.4%; TV:0%), 40.3% in HIV−/PrEP+ MSM (CT:13.8%; MG:19.4%; NG:14.8%; TV:0.4%), and 30.8% in HIV+ MSM (CT:10.1%; MG:18.4%; NG:8.6%; TV:0.1%). Being HIV+ (OR 1.7, 95%-CI 1.3–2.2), using PrEP (OR 2.0, 95%-CI 1.5–2.7), having > 5 sex partners (OR:1.65; 95%-CI:1.32–2.01.9), having condomless sex (OR:2.11.9; 95%-CI:1.65–2.86), and using party drugs (OR:1.65; 95%-CI:1.32–2.0) were independent risk factors for being tested positive for at least one STI. Conclusions We found a high STI-prevalence in MSM in Germany, especially in PrEP users, frequently being asymptomatic. As a relevant proportion of PrEP users will not use a condom, counselling and comprehensive STI screening is essential and should be low threshold and preferably free of cost. Counselling of PrEP users should also address use of party drugs.

Online algorithms that allow a small amount of migration or recourse have been intensively studied in the last years. They are essential in the design of competitive algorithms for dynamic problems, where objects can also depart from the instance. In this work, we give a general framework to obtain so called robust online algorithms for a variety of dynamic problems: these online algorithms achieve an asymptotic competitive ratio of \(\gamma +\epsilon \) with migration \(O(1/\epsilon )\), where \(\gamma \) is the best known offline asymptotic approximation ratio. For our framework, we require only two ingredients: (i) the existence of an online algorithm for the static case (without departures) that provides a provably good solution compared to the total volume of the instance and (ii) that the optimal solution always exceeds this total volume. If these criteria are met, we can complement the online algorithm with any offline algorithm.

Background Some male heterosexual clients prefer to visit a cross-border Female Sex Worker (FSW) because of cheaper sex and unsafe sex practices, and may therefore be at risk for sexually transmitted infections (STI). The objective of this study was to assess whether having commercial cross-border sex is an independent risk factor for being diagnosed with a STI. Methods An observational retrospective study was performed using data of 8 Dutch STI clinics bordering Germany, between 2011 and 2013. All male heterosexual clients of FSWs were selected and data on country of FSW visit and occurrence of STI were used for multivariable regression analysis. Results The study population consisted of 2664 clients of FSW. Most clients visited the Netherlands (82.4%), followed by visits to another country (beyond cross-border) (9.9%) and cross-border visits (7.8%). Clients of FSW were less likely to be STI positive when they were younger than 25 years(OR = 0.6, 95%CI 0.4 to 0.8 25–44 years and OR = 0.5, 95%CI 0.4 to 0.7 older than 45 years), and more likely when they had 20 or more sex partners in the last 6 months (OR = 2.9, 95%CI 1.9 to 4.4), did not use a condom during last sexual contact (OR = 2.2, 95%CI 1.6 to 2.9) and made cross-border visits (OR = 1.7, 95%CI 1.1 to 2.6). Conclusions As cross-border visits appears to be a novel independent risk factor for STI in clients of FSW, this group should therefore be advised on STI prevention.

International audience; We study approximation algorithms for the problem of minimizing the makespan on a set of machines with uncertainty on the processing times of jobs. In the model we consider, which goes back to Bertsimas et al. [3], once the schedule is defined an adversary can pick a scenario where deviation is added to some of the jobs' processing times. Given only the maximal cardinality of these jobs, and the magnitude of potential deviation for each job, the goal is to optimize the worst-case scenario. We consider both the cases of identical and unrelated machines. Our main result is an EPTAS for the case of identical machines. We also provide a 3-approximation algorithm and an inapproximability ratio of 2 − for the case of unrelated machines.

We consider the classical scheduling problem on parallel identical machines to minimize the makespan. There is a long history of study on this problem, focusing on exact and approximation algorithms. It is thus natural to consider whether these algorithms can be further improved in terms of running times. We provide strong lower bounds on the running times of exact and approximation schemes for the classical scheduling problem based on Exponential Time Hypothesis, showing that the best known approximation and exact algorithms are almost the best possible in terms of the running time.

Scheduling on Unrelated Machines is a classical optimization problem where [Formula: see text] jobs have to be distributed to [Formula: see text] machines. Each of the jobs [Formula: see text] has on machine [Formula: see text] a processing time [Formula: see text]. The goal is to minimize the makespan, i.e., the maximum completion time of the longest-running machine. Unless [Formula: see text], this problem does not allow for a polynomial-time approximation algorithm with a ratio better than [Formula: see text]. A natural scenario is however that many machines are of the same type, like a CPU and GPU cluster: for each of the [Formula: see text] machine types, the machines [Formula: see text] of the same type [Formula: see text] satisfy [Formula: see text] for all jobs [Formula: see text]. For the case where the number [Formula: see text] of machine types is constant, this paper presents an approximation scheme, i.e., an algorithm of approximation ratio [Formula: see text] for [Formula: see text], with an improved running time only single exponential in [Formula: see text].

International audience; This paper studies Upper Domination, i.e., the problem of computing the maximum cardinality of a minimal dominating set in a graph with respect to classical and parameterised complexity as well as approximability.

Sexuell übertragbare Erkrankungen (STI) können in der Schwangerschaft zu Fehlbildungen, Entwicklungsstörungen und Erkrankungen des Fötus bzw. Embryos führen. Der Artikel erläutert die epidemiologische Lage sowie die klinische Relevanz des Themas für die Schwangerenbetreuung und Geburtshilfe.

Sexually transmitted infections (STIs) can impair sexual health. Surveillance and study data were used to provide an overview over STIs in Germany. We estimated 3900 new HIV diagnoses in 2015. Of newly diagnosed infections, 57% were attributed to men who have sex with men (MSM). It was further estimated that there were 3200 new HIV infections and 84,700 people living with HIV in 2015. A total of 6834 syphilis infections were recorded in 2015, which corresponds to an increase of 149% since 2009. The incidence in men was 16-times higher than in women. Of syphilis infections, 85% could be attributed to MSM. Antimicrobial resistance of gonococci against the broad-spectrum antibiotic cefixime decreased between 2014 and 2016 after a change of therapy guidelines and remained stable on a low level regarding the antibiotic ceftriaxone. After an increase of resistance against the antibiotic azithromycin to 11.3% in 2015, we observed a decreasing trend in 2016. Between 2013 and 2015, 2,355,336 chlamydia tests were reported through the chlamydia sentinel network. Of these, 92.5% of samples were from women. Uptake for screening for women

We consider a special case of the scheduling problem on unrelated machines, namely the restricted assignment problem with two different processing times. We show that the configuration LP has an integrality gap of at most $$\frac{5}{3} \approx 1.667$$ for this problem. This allows us to estimate the optimal makespan within a factor of $$\frac{5}{3}$$ , improving upon the previously best known estimation algorithm with ratio $$\frac{11}{6} \approx 1.833$$ due to Chakrabarty et al. (in: Proceedings of the twenty-sixth annual ACM-SIAM symposium on discrete algorithms (SODA 2015), pp 1087–1101, 2015).

Am 5.2.16 fand am Robert-Koch-Institut in Berlin ein Expertentreffen zum Thema „Schnelltests in der Diagnostik sexuell ubertragbarer Infektionen“ statt. Das Ziel dieser Tagung war, die in einem vorangegangenen Treffen im Januar 2012 erarbeitete Bewertung der Schnelltests fur den Einsatz in der Infektionsdiagnostik von HIV, HBV, HCV, T. pallidum, C. trachomatis und N. gonorrhoeae in „niedrigschwelligen Einrichtungen“ unter Berucksichtigung neuer Erkenntnisse und Entwicklungen dem aktuellen Stand anzupassen. Die von der Bundesregierung kurzlich beschlossene Strategie zur Eindammung von HIV, Hepatitis B und C und anderen sexuell ubertragbaren Infektionen beschreibt einen Mangel an Testmoglichkeiten und verfolgt eine Steigerung der Testangebote und einen besseren Zugang. Eine wichtige Option um Testbarrieren zu senken, reprasentiert der Einsatz von Schnelltests, die als niedrigschwelliges Testangebot in Beratungsstellen angeboten werden und auch als Heimtests durchgefuhrt werden konnen. Basierend auf den in klinischen Studien evaluierten Leistungsmerkmalen sind einige HIV-, HCV- und Syphilis-Schnelltests durchaus als point-of-care Test (POCT) geeignet. Fur C. trachomatis und N. gonorrhoeae erreichen nur PCR-basierte POCTs eine ausreichende diagnostische Genauigkeit. Der Einsatz von Schnelltest ist in Deutschland an bestimmte Vorgaben des IfSG und MPG gebunden. Die Abgabe von HIV-Diagnostika an Privatpersonen (zwecks Heimtestung) ist in Deutschland untersagt (§ 11, MPG). Die Feststellung und Ubermittlung einer Infektionskrankheit ist einem Arzt vorbehalten und darf auch nicht als Ferndiagnose erfolgen (§ 24, IfSG). Daruber hinaus unterliegen Schnelltests, wie alle labormedizinischen Analysen einer Qualitatssicherung entsprechend den Richtlinien der Bundesarztekammer.

Background Despite high hepatitis C virus (HCV) treatment rates, HCV incidence among human immunodeficiency virus (HIV)–infected men who have sex with men (HIV-infected MSM) in Germany rose before HCV direct-acting antivirals (DAAs). We model what intervention can achieve the World Health Organization (WHO) elimination target of an 80% reduction in HCV incidence by 2030 among HIV-infected MSM in Berlin. Methods An HCV transmission model among HIV-diagnosed MSM was calibrated to Berlin (rising HCV incidence and high rates of HCV testing and treatment). We modeled the HCV incidence among HIV-diagnosed MSM in Berlin until 2030 (relative to 2015 WHO baseline) under scenarios of DAA scale-up with or without behavior change (among HIV-diagnosed MSM and/or all MSM). Results Continuing current treatment rates will marginally reduce the HCV incidence among HIV-diagnosed MSM in Berlin by 2030. Scaling up DAA treatment rates, beginning in 2018, to 100% of newly diagnosed HCV infections within 3 months of diagnosis and 25% each year of previously diagnosed and untreated HCV infections could reduce the HCV incidence by 61% (95% confidence interval, 55.4%–66.7%) by 2030. The WHO target would likely be achieved by combining DAA scale-up with a 40% reduction in HCV transmission among HIV-diagnosed MSM and a 20% reduction among HIV-undiagnosed or HIV-uninfected MSM. Discussion HCV elimination among HIV-infected MSM in Berlin likely requires combining DAA scale-up with moderately effective behavioral interventions to reduce risk among all MSM.

Introduction Until September 2019, pre‐exposure prophylaxis (PrEP) with tenofovir disoproxil/emtricitabine for HIV prevention was not covered by health insurance plans in Germany, and was only available through private prescriptions with self‐pay or through informal non‐prescription sources. The objective of this study was to investigate the proportion of informal PrEP use among PrEP users and to identify factors of public health relevance that might be associated with informal PrEP use. Methods We conducted a cross‐sectional study recruiting PrEP users independent of their PrEP source. Clients from anonymous community testing checkpoints, users of three dating apps for men who have sex with men residing in Germany and users of a PrEP community website, were recruited to complete a short anonymous online survey. Participants were recruited between 24 July and 3 September 2018. The results were analysed using univariable and multivariable logistic regressions. Results We recruited 2005 participants currently using PrEP. The median age was 38 years, and 80.3% of the participants identified themselves as male (missing: 19.1%). Overall, 71.6% obtained PrEP through medical services with a private prescription or a clinical trial, and 17.4% obtained PrEP through informal sources (missing: 11.0%). The most common informal sources were ordering online from another country (8.8%), travel abroad (3.6%), and friends (2.5%). Factors associated with informal PrEP use were on demand/intermittent dosing (adjusted OR: 3.5, 95% CI 2.5 to 5.0) and not receiving medical tests during PrEP use (adjusted OR: 3.2, 95% CI 2.0 to 5.2). In addition, informal PrEP users who did not take PrEP daily had a strongly increased risk of starting PrEP without prior medical tests (adjusted stratum‐specific OR = 31.7, 95% CI 4.6 to 219.5). Conclusions Informal PrEP use was associated with a higher risk of not getting tested before and during PrEP use, which could lead to HIV infections resistant to tenofovir and emtricitabine if people with undiagnosed HIV use PrEP. Health insurance plans that cover PrEP and the accompanying routine tests could ensure adequate medical supervision of PrEP users and reduce barriers to PrEP use. Our findings strongly support the implementation of PrEP programmes in countries with similar patterns of informal PrEP use.

Background HIV-positive (HIV+) MSM often show higher STI-prevalence than HIV-negative MSM (HIV-). Approval of HIV pre-exposure prophylaxis (PrEP) in Germany might have influenced sexual behaviour and STI-prevalence of HIV- MSM. We estimated STI-prevalence and risk factors amongst HIV- and HIV+ MSM in Germany to plan effective interventions. Methods We conducted a nationwide, cross-sectional study between February and July 2018. Thirteen MSM-friendly STI-clinics screened MSM for Chlamydia trachomatis (CT), Mycoplasma genitalium (MG), Neisseria gonorrhea (NG), and Trichomonas vaginalis (TV) using self-collected rectal and pharyngeal swabs, and urine samples, and APTIMA® STI-assays. We oversampled HIV+ MSM. We collected information on sociodemographics, HIV-status, clinical symptoms, sexual behaviour within last 6 months, and PrEP-use. We combined HIV status and PrEP use for defining risk groups, and used multivariate logistic regression to identify risk factors for STI. Results 2,303 MSM were included: 50.5% HIV+, median age 39 years. Median number of male sex partners was 5. 57.2% reported unprotected receptive anal intercourse (URAI), 43.0% use of party drugs. 78.9% had a STI history, 32.1% of STI+ MSM reported STI-related symptoms. 27.6% of HIV- MSM used PrEP. Overall STI-prevalence was 25.0% in HIV-/PrEP- MSM (CT:7.2%; MG:14.2%; NG:7.4%; TV:0%), 40.3% in HIV-/PrEP+ MSM (CT:13.8%; MG:19.4%; NG:14.9%; TV:0.4%), and 30.8% in HIV+ MSM (CT:10.1%; MG:18.4%; NG:8.6%; TV:0.1%). Independent risk factors were HIV/PrEP-status (HIV-/PrEP+ OR:1.4; 95%-CI:1.0–2.0; HIV+ OR:1.5; 95%-CI:1.1–1.9), >5 sex partners (OR:1.5; 95%-CI:1.2–1.9), URAI (OR:2.0; 95%-CI:1.5–2.6), and use of party drugs (OR:1.5; 95%-CI:1.2–2.0). Conclusion We found a high STI-prevalence in MSM in Germany, especially in PrEP users, frequently being asymptomatic. Higher STI prevalence in PrEP users than in HIV+ MSM was partly explained by differences in risk behaviour. As a relevant proportion of PrEP users will not use a condom while using PrEP, counselling and comprehensive STI screening is essential. Counselling of PrEP users should address condom use and party drugs. Disclosure No significant relationships.

Background Mycoplasma genitalium (MG) is one of the most common bacterial sexually transmitted infections (STI). Nevertheless, knowledge about the immune response is scarce and seroprevalence has only been assessed in selected populations. In HIV-negative blood donors seroprevalence was 5.5%, in patients with pelvic inflammatory disease 17%. We estimated MG seroprevalence in the general adult population in Germany. Methods We retrospectively analysed sera of the population-based German National Health Interview and Examination Survey 1998 for MG antibodies using a pre-validated, multiplex, fluorescent bead-based assay. To avoid cross-reactivity, two unconserved regions of adhesion proteins, MgPaN and rMgPa were chosen as antigens. The thresholds for seropositivity were set at 1000 median fluorescence intensity units by visual inspection of inflection points. Overall seropositivity for MG was defined as concomitant seropositivity for both antigens. To assure representativeness, survey weights were applied for calculation of prevalence and 95% confidence intervals(CI). Design-based F was computed as test of independence. Results Sera of 6038 participants were analysed. Participants were aged 17–79 years (y) (median 44y), 51% were female. Overall weighted seroprevalence was 6.5% (95%CI: 5.7–7.3%), and by age-group 17–19y 0.3% (0.1–1.5%), 20–24y 1.9% (0.9–3.8%), 25–29y 6.7% (4.6–9.8%), 30–39y 9.1% (7.4–11.1%), 40–49y 10.8% (8.9–13.0%), 50–59y 4.5% (3.4–5.9%), 60–69y 3.3% (2.2–5.1%), and 70–79y 4.6% (2.9–7.4%). In the age-group 20–29y, women had a higher seroprevalence (7.5%, 95%CI: 5.0–11.1%) than men (2.1%, 95%CI: 1.1–4.0%; p=0.001). Conclusion Compared to other studies, our results for MG seroprevalence in the general adult population in Germany are plausible. The earlier increase in women is similar to the pattern in other STI such as Chlamydia trachomatis infection. Seroprevalence dropped in participants aged 50 or more but remained stable at a low level until old age, indicating long antibody persistence or continuous sexual interactions in parts of the population. However, longitudinal studies are necessary to clarify immunological processes. Disclosure No significant relationships.

Background German national guidelines recommend ceftriaxone combined with azithromycin for Neisseria gonorrhoeae (NG) treatment since 2014. The Gonococcal-Resistance-Network (GORENET) monitors gonococcal antimicrobial resistance (AMR) in Germany. The aim is to assess whether national guidelines are still effective in Germany and which factors affect higher minimum inhibitory concentrations (MICs). Methods GORENET laboratories sent NG isolates to the conciliar laboratory for centralized retesting of AMR using E-test. We included infection year, sex, age, infection site and clinical service type in the analysis. Geometric means were calculated for MICs for infection year. The effects of infection year, sex, age, infection site and clinical service type on MICs for ceftriaxone, cefixime, and azithromycin were investigated by multiple linear regression. Results Overall, 278 (2014), 303 (2015), 438 (2016) and 409 (2017) isolates were analysed. Of these, 90% of isolates came from men. Median age was 33 years (IQR: 25–44). Cumulative geometric means of MICs 2014–2017 were 0.006 µg/ml for ceftriaxone, 0.022 µg/ml for cefixime, and 0.185 µg/ml for azithromycin. In adjusted analysis, MICs decreased for ceftriaxone, cefixime and azithromycin by 0.74 (CI-95% 0.70–0.79), 0.89 (CI-95% 0.87–0.92) and 0.79 (CI-95% 0.75–0.83) per year, respectively. For ceftriaxone, isolates from urology (1.40; 95%-CI 1.15–1.69) and other service types (1.39; 95%-CI 1.10–1.77) compared to internal medicine, and from women (1.58; 95%-CI 1.14–2.18) were associated with increased MICs. Regarding cefixime isolates collected from urology (1.14; 95%-CI 1.02–1.28) compared to internal medicine, and from women (1.41; 95%-CI 1.18–1.69) were associated with increased MICs. For azithromycin, isolates from urology (0.82; 95%-CI 0.70–0.97) compared to internal medicine, and from women (0.77; 95%-CI 0.59–1.00) were associated with decreased MICs. Conclusion Treatment options as recommended by German national guidelines are still applicable. The lower MICs after 2014 may be due to the change of national treatment guidelines in 2014. Differences in MICs regarding service types and sex need to be further investigated. Disclosure No significant relationships.

Background An opportunistic screening program for Chlamydia trachomatis (CT) was introduced in Germany in 2008, targeting sexually active women under the age of 25. The program suffers from low coverage (∼12%) and its impact on the epidemiology of CT in the German setting remains unclear. As CT is not notifiable in Germany, we used alternative data sources to describe CT-epidemiology in the context of the screening program. Methods Urine-PCR results from two population-based, nationwide health surveys of adults (DEGS, 2008–2011, subsample=2,364) and minors (KiGGS-Wave 2, 2014–2017, subsample=619) were analyzed. Weighted CT-prevalences were estimated for adults. Prevalence estimation for age-subgroups and adolescents was not possible due to high coefficients of variation, instead unweighted CT-positive proportions were calculated in an explorative analysis. Data from a CT laboratory sentinel system were used to obtain the number of screening tests performed and the proportion of positive results by age and year. Results The weighted prevalence of CT in the general German population aged 18–44 was estimated at 1.2% (95% confidence interval (95%CI): 0.6%–2.2%) among women and 1.9% (95%CI: 1.2%–3.0%) among men. The highest unweighted CT-positive proportions were found in the younger age groups in both women (18–24y: 2.4%, 95%CI 1.1%–5.0%; 25–34y: 1.5%, 95%CI 0.7%–3.3%) and men (18–24y: 2.0%, 95%CI 0.9%–4.4%; 25–34y: 2.9%, 95%CI 1.6%–5.2%). Among 15- to 17-year-old girls, an unweighted CT-positive proportion of 6.2% (95%CI 2.9%–12.6%) was found. Sentinel data from 2014–2016 (467,474 screening-tests of 15–24 year-old women) showed positive-result proportions of 3.4% (95%CI 3.1%–3.7%), 6.1% (95%CI 5.9%–6.4%) and 3.9% (95%CI 3.7%–4.0%) among 15-, 19- and 24-year-olds, respectively. Conclusion The German screening program seems to correctly target the women most at risk and may thus prevent cases of CT-sequelae. However, through its low coverage and the exclusion of men, who serve as a reservoir for the infection, the program is not likely to reduce CT-prevalence effectively. Disclosure No significant relationships.

Background Current epidemiological studies demonstrate a high prevalence of Mycoplasma genitalium (MG) infections in high-risk groups, especially MSM. Owing to the widespread macrolide resistance the European Guideline on MG infections recommend complementing the molecular detection of MG with an assay capable of detecting macrolide resistance-associated mutations. Macrolide resistance is caused by a single nucleotide polymorphism (SNP) in region V of the 23S rRNA gene. Two nucleotide positions in the 23S rRNA gene have been associated with azithromycin resistance: A2058 and A2059. Methods The Aptima M. genitaliumAssay® was used for the initial detection on the Panther® system. A hydrolysis probe real-time PCR on theOpen Channelof the PantherFusion® system for automated reflex testing after MG positive results was established and validated. The Open Channelof the instrument allows the use of custom primers and probes on the PantherFusion® system. Minor groove binder (MGB) hydrolysis probes were used for accurate and reliable SNP discrimination at position 2058/2059. The workflow enables an automated analysis process including DNA extraction, PCR setup, and results interpretation. Using the open channel 300 samples could be genotyped within an 8 h working day. Results 60 MG positive clinical samples were tested. The laboratory developed test (LDT) was able to detect the wild type variant in 20 samples and the A2058G/A2059G mutations in 22 samples. All results were confirmed by amplicon sequencing and commercially available test system. 18 (30%) samples did not show any typing result either using different LDT or commercial test system. Conclusion MG positive samples can be typed for macrolide resistance using our LDT on the same platform during one run. The combination of a MG high-throughput test followed by macrolide resistance testing improves the efficiency of large-scale epidemiological resistance surveillance. However, highly sensitive TMA assay might result in a significant number of non-typable samples. Further studies are needed to improve the sensitivity and explanatorypower of MG resistance testing. Disclosure No significant relationships.

Background The widespread antimicrobial resistance (AMR) of Neisseria gonorrhoeae (NG) is a serious problem for the treatment of gonorrhoea. Because NG infections are not reportable in Germany, only limited data on disease epidemiology and antimicrobial susceptibility patterns are available. The Gonococcal Resistance Network (GORENET) monitors trends of NG AMR in Germany and links this to epidemiological data and NG multiantigen sequence typing (NG-MAST) data to guide treatment algorithms and target future prevention strategies. Methods Between April 2014 and December 2018, NG isolates and data on patient-related information were collected from laboratories nationwide and centralized susceptibility testing using E-test was performed. Susceptibility results for cefixime, ceftriaxone, azithromycin, ciprofloxacin and penicillin were defined according to EUCAST 4.0 standards. Results Of 2115 isolates, 91.6% of isolates were from men. The most frequently tested materials among men were urethral (92.4%) and rectal swabs (3.8%), and among women mainly endocervical swabs (80.9%). Resistance to ceftriaxone (MIC ≥0.125 mg/L) occurred only sporadically (0–0.3%) during the entire observation period (2015 and 2018), while 1.0–2.1% of isolates were resistant to cefixime (MIC ≥0.125 mg/L). Proportion of isolates resistant to azithromycin (MIC ≥ 0.5 mg/L) was 11.4% (2014), 11.3% (2015), 4.3% (2016), 3.7% (2017), 9.4% (2018). 53.4–71.7% were resistant to ciprofloxacin, and 14.2–24.3.1% were resistant to penicillin. Conclusion Resistance to ceftriaxone and to cefixime was low, whereas azithromycin resistance showed a discontinuous presentation with partly high levels during the observation period. Rates of ciprofloxacin and penicillin resistance were very high. According to the current national guidelines, ceftriaxone 1-2g IV and azithromycin 1,5g orally are usually used in dual therapy. Shortly revised national guidelines will state that use of azithromycin should be avoided if possible if a test of cure can be guaranteed and a susceptibility test is available. Continued surveillance of NG AMR remains relevant to ensure efficient disease management. Disclosure No significant relationships.

Background Clinical types of specimen as well as rising sample numbers during a STI studies, pose a challenge to the capability of the lab. Workflow optimization and automation strategies are crucial to enable high throughput investigations with a maximum of efficiency if diagnostic data have to be combined with additional information content. Methods In our molecular laboratory we have established an optimized the sample management, automated extraction and detection protocols using the Panther® instrument, bidirectional order entry and reporting setting followed by a digital archiving and data management procedure. The workflow combines self-sampling from different anatomical sites, automated data input and sample management including LIS based registration of the sample tubes. The Panther® protocol combines target detection of different STI pathogens. The results are transferred directly into the LIS for validation and reporting. The sample tubes are archived including an electronic place marker for subsequent investigation. Results The workflow enables us to proceed up to 600 samples in a 10 hours working day. We handle 250–500 samples per day. During the German MSM screening study 2018 we investigated 6900 additional samples resulting in 27600 analytical data points and more than 300.000 sociodemographic information within 3 month. Analytical result data were continuously linked to collected questionnaire information on sociodemographics (e.g. clinical symptoms, sexual behavior, PrEP-use, etc.). Result reports were delivered every day and cumulative data sets were exported from LIS for epidemiological evaluation every week. Conclusion We have adapted a workflow for laboratory requirements of epidemiologic STI studies. This is essential for efficient data management processes. By integrating molecular instruments into a combined sample management process automation has become a fundamental principle in laboratory processes but is also indispensable for conducting STI investigations. We have already implemented the process successfully during the ‘MSM Screening Study 2018’ and the ongoing ‘BRAHMS-Study 2018’. Disclosure No significant relationships.

Background Neisseria gonorrhoeae (NG) infections are not reportable in Germany. The Gonococcal Resistance Network (GORENET) is a laboratory network to monitor antimicrobial resistance (AMR) in Germany, linking data from sequence typing to epidemiological data. We described prevalence of gonococcal sequence types in Germany and associations to AMR to improve future treatment and prevention strategies. Methods NG isolates collected between April 2014 and December 2017 were tested by E-test and sequence typed by NG multiantigen sequence typing (NG-MAST). For sequence typing, DNA was extracted and internal fragments of porB and tbpB were amplified by polymerase chain reaction. Fragments were sequenced by Sanger sequencing and evaluated using a global database (www.ng-mast.net). Genogroups were assigned to sequence types which shared one allele and exhibited ≥99% homogeneity in the other allele. Results 1220 isolates were sequence typed (106 in 2014, 96 in 2015, 525 in 2016, and 495 in 2017). In total, we detected 422 different sequence types that grouped into 17 genogroups. Among the most prevalent genogroups were G2400 (6.8%), G1407 (6.8%), G5441 (6.2%), G25 (5.6%), G2992 (5.5%) and G10557 (5.3%). The multi-resistant G1407 and G2400 were most prevalent in 2014 (12.4% and 10.5%, respectively) and declined to 6.1% and 7.3% in 2017. Two new genogroups, G11461 (3.6%) and G17420 (2.1%), emerged showing high prevalence in 2017 and no association to extended-spectrum cephalosporin resistance. Furthermore, a novel genogroup-association with cefixime resistance and reduced cephalosporin susceptibility was identified. Conclusion From 2014 to 2017 prevalence of G1407 declined and two novel extended-spectrum cephalosporin sensitive clones G11461 and G17420 seem to have replaced the multi-drug resistance clone G1407. To verify these results, continuous testing with an increased number of isolates should be performed. Disclosure No significant relationships.

We investigate the scheduling of $n$ jobs divided into $c$ classes on $m$ identical parallel machines. For every class there is a setup time which is required whenever a machine switches from the processing of one class to another class. The objective is to find a schedule that minimizes the makespan. We give near-linear approximation algorithms for the following problem variants: the non-preemptive context where jobs may not be preempted, the preemptive context where jobs may be preempted but not parallelized, as well as the splittable context where jobs may be preempted and parallelized. We present the first algorithm improving the previously best approximation ratio of $2$ to a better ratio of $3/2$ in the preemptive case. In more detail, for all three flavors we present an approximation ratio $2$ with running time $\mathcal{O}(n)$, ratio $3/2+\varepsilon$ in time $\mathcal{O}(n\log 1/\varepsilon)$ as well as a ratio of $3/2$. The $(3/2)$-approximate algorithms have different running times. In the non-preemptive case we get time $\mathcal{O}(n\log (n+\Delta))$ where $\Delta$ is the largest value of the input. The splittable approximation runs in time $\mathcal{O}(n+c\log(c+m))$ whereas the preemptive algorithm has a running time $\mathcal{O}(n \log (c+m)) \leq \mathcal{O}(n \log n)$. So far, no PTAS is known for the preemptive problem without restrictions, so we make progress towards that question. Recently Jansen et al. found an EPTAS for the splittable and non-preemptive case but with impractical running times exponential in $1/\varepsilon$.

Machine scheduling is a fundamental optimization problem in computer science. The task of scheduling a set of jobs on a given number of machines and minimizing the makespan is well studied and among other results, we know that EPTAS's for machine scheduling on identical machines exist. Das and Wiese initiated the research on a generalization of makespan minimization, that includes so called bag-constraints. In this variation of machine scheduling the given set of jobs is partitioned into subsets, so called bags. Given this partition a schedule is only considered feasible when on any machine there is at most one job from each bag. Das and Wiese showed that this variant of machine scheduling admits a PTAS. We will improve on this result by giving the first EPTAS for the machine scheduling problem with bag-constraints. We achieve this result by using new insights on this problem and restrictions given by the bag-constraints. We show that, to gain an approximate solution, we can relax the bag-constraints and ignore some of the restrictions. Our EPTAS uses a new instance transformation that will allow us to schedule large and small jobs independently of each other for a majority of bags. We also show that it is sufficient to respect the bag-constraint only among a constant number of bags, when scheduling large jobs. With these observations our algorithm will allow for some conflicts when computing a schedule and we show how to repair the schedule in polynomial-time by swapping certain jobs around.