2019 |
Ledo, A; Schub, D; Ziller, C; Enders, M; Stenger, T; Gärtner, BC; Schmidt, T; Meyer, T; Sester, M Brain, behavior, and immunity, 2019. @article{Ledo.2019, title = {Elite athletes on regular training show more pronounced induction of vaccine-specific T-cells and antibodies after tetravalent influenza vaccination than controls}, author = {A Ledo and D Schub and C Ziller and M Enders and T Stenger and BC G\"{a}rtner and T Schmidt and T Meyer and M Sester}, doi = {10.1016/j.bbi.2019.09.024}, year = {2019}, date = {2019-01-01}, journal = {Brain, behavior, and immunity}, abstract = {Compliance of elite athletes with vaccination recommendations is low mainly based on concerns about side-effects and perceived poor vaccine efficacy due to continued physical training. We therefore employed seasonal influenza vaccination to investigate the effect of regular physical training on vaccine-induced cellular and humoral immunity in elite athletes and controls. Lymphocyte subpopulations and vaccine-specific T-cells were quantified and functionally characterized from 45 athletes and 25 controls before, and 1, 2 and 26 weeks after vaccination. Moreover, influenza-specific antibodies and their neutralizing function were quantified. Both groups showed a significant increase in vaccine-reactive CD4 T-cell levels which peaked one week after vaccination (p textless 0.0001). The increase was significantly more pronounced in athletes (4.1-fold) compared to controls (2.3-fold; p = 0.0007). The cytokine profile changed from multifunctional T-cells co-producing IFNtextgreekg, IL-2 and TNFtextgree\k{a} to cells with restricted cytokine expression. This change in functionality was associated with a significant increase in CTLA-4 expression (p textless 0.0001), which again was more pronounced in athletes. Likewise, the increase in neutralizing antibodies was stronger in athletes (p = 0.004 for H1N1; p = 0.032 for H3N2). In conclusion, both groups mounted a strong vaccine-specific cellular and humoral immunity after standard vaccination. The more pronounced increase in specific T-cells and neutralizing antibodies indicates that high frequency and intensity of training enhance vaccine-responses in elite athletes.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Compliance of elite athletes with vaccination recommendations is low mainly based on concerns about side-effects and perceived poor vaccine efficacy due to continued physical training. We therefore employed seasonal influenza vaccination to investigate the effect of regular physical training on vaccine-induced cellular and humoral immunity in elite athletes and controls. Lymphocyte subpopulations and vaccine-specific T-cells were quantified and functionally characterized from 45 athletes and 25 controls before, and 1, 2 and 26 weeks after vaccination. Moreover, influenza-specific antibodies and their neutralizing function were quantified. Both groups showed a significant increase in vaccine-reactive CD4 T-cell levels which peaked one week after vaccination (p textless 0.0001). The increase was significantly more pronounced in athletes (4.1-fold) compared to controls (2.3-fold; p = 0.0007). The cytokine profile changed from multifunctional T-cells co-producing IFNtextgreekg, IL-2 and TNFtextgreeą to cells with restricted cytokine expression. This change in functionality was associated with a significant increase in CTLA-4 expression (p textless 0.0001), which again was more pronounced in athletes. Likewise, the increase in neutralizing antibodies was stronger in athletes (p = 0.004 for H1N1; p = 0.032 for H3N2). In conclusion, both groups mounted a strong vaccine-specific cellular and humoral immunity after standard vaccination. The more pronounced increase in specific T-cells and neutralizing antibodies indicates that high frequency and intensity of training enhance vaccine-responses in elite athletes. |
Kohmer, N; Nagel, A; Berger, A; Enders, M; Hamprecht, K; Korn, K; Kortenbusch, M; Überla, K; Rabenau, H F Laboratory diagnosis of congenital CMV infection in newborns: Impact of pre-analytic factors Artikel Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology, 115 , S. 32–36, 2019, ISSN: 1386-6532. @article{Kohmer.2019, title = {Laboratory diagnosis of congenital CMV infection in newborns: Impact of pre-analytic factors}, author = {N Kohmer and A Nagel and A Berger and M Enders and K Hamprecht and K Korn and M Kortenbusch and K \"{U}berla and H F Rabenau}, doi = {10.1016/j.jcv.2019.03.017}, issn = {1386-6532}, year = {2019}, date = {2019-01-01}, journal = {Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology}, volume = {115}, pages = {32--36}, abstract = {BACKGROUND To identify infants with congenital cytomegalovirus (cCMV) saliva polymerase chain reaction (PCR) is an ideal screening method. However, there are only few data on the influence of pre-analytic factors on the analytical sensitivity of the CMV PCR. OBJECTIVES This study aimed to evaluate the performance of different swabbing materials, transport time and initial virus concentration regarding to the efficacy of recovery of CMV-DNA. STUDY DESIGN Two CMV suspensions containing a high or low concentration of the laboratory strain AD 169 were prepared as test samples. Sampling was simulated by immersion of different swabs in these CMV suspensions and storing the swabs dry or in specified transport media. Transport conditions were modeled by storing the samples for defined time periods prior to DNA extraction and quantitative PCR analyses. Parallel analyses in two different laboratories allowed determination of lab to lab consistency. RESULTS The duration of storage under the conditions analysed did not have a major effect on the recovery efficiency for the swabbing materials tested. With exception of flocked dry swabs, all tested swabbing materials demonstrated good recovery of CMV DNA. The flocked swab/eNAT system showed the best overall performance. CONCLUSIONS All tested swabbing materials (with exception of the flocked dry swabs) seem to be well suited for recovery of CMV DNA and appropriate for use for the diagnosis of cCMV infection in symptomatic cases and in general cCMV screening programs of newborns.}, keywords = {}, pubstate = {published}, tppubtype = {article} } BACKGROUND To identify infants with congenital cytomegalovirus (cCMV) saliva polymerase chain reaction (PCR) is an ideal screening method. However, there are only few data on the influence of pre-analytic factors on the analytical sensitivity of the CMV PCR. OBJECTIVES This study aimed to evaluate the performance of different swabbing materials, transport time and initial virus concentration regarding to the efficacy of recovery of CMV-DNA. STUDY DESIGN Two CMV suspensions containing a high or low concentration of the laboratory strain AD 169 were prepared as test samples. Sampling was simulated by immersion of different swabs in these CMV suspensions and storing the swabs dry or in specified transport media. Transport conditions were modeled by storing the samples for defined time periods prior to DNA extraction and quantitative PCR analyses. Parallel analyses in two different laboratories allowed determination of lab to lab consistency. RESULTS The duration of storage under the conditions analysed did not have a major effect on the recovery efficiency for the swabbing materials tested. With exception of flocked dry swabs, all tested swabbing materials demonstrated good recovery of CMV DNA. The flocked swab/eNAT system showed the best overall performance. CONCLUSIONS All tested swabbing materials (with exception of the flocked dry swabs) seem to be well suited for recovery of CMV DNA and appropriate for use for the diagnosis of cCMV infection in symptomatic cases and in general cCMV screening programs of newborns. |
Kagan, K O; Enders, M; Schampera, M S; Baeumel, E; Hoopmann, M; Geipel, A; Berg, C; Goelz, R; de Catte, L; Wallwiener, D; Brucker, S; Adler, S P; Jahn, G; Hamprecht, K Ultrasound in obstetrics & gynecology, 53 (3), S. 383–389, 2019, ISSN: 0960-7692. @article{Kagan.2019b, title = {Prevention of maternal-fetal transmission of CMV by hyperimmunoglobulin (HIG) administered after a primary maternal CMV infectionin early gestation}, author = {K O Kagan and M Enders and M S Schampera and E Baeumel and M Hoopmann and A Geipel and C Berg and R Goelz and L de Catte and D Wallwiener and S Brucker and S P Adler and G Jahn and K Hamprecht}, doi = {10.1002/uog.19164}, issn = {0960-7692}, year = {2019}, date = {2019-01-01}, journal = {Ultrasound in obstetrics & gynecology}, volume = {53}, number = {3}, pages = {383--389}, abstract = {OBJECTIVE To examine the efficacy of biweekly hyperimmunoglobulin (HIG) administration to women with first trimester CMV infection for preventing maternal-fetal transmission of CMV. METHODS Subjects were 40 pregnant women with a primary CMV infection with a median gestational age at diagnosis of 9.6 weeks with a range of 5.1 to 14.3 weeks' gestation. On average, HIG administration started at 11.1 weeks and continued until 16.6 weeks' gestation. Within this interval, HIG was administered between 2 and 6 times. While CMV IgG monitoring showed periodic fluctuations during biweekly HIG administration cycles, high CMV IgG avidity indices remained stable over the whole treatment period. The results were compared with a historic cohort with first trimester CMV infection without treatment that also had an amniocentesis at about 20 weeks RESULTS: Each subject had amniocentesis performed. Maternal-fetal transmission before amniocentesis occurred in only one of the 40 cases (2.5%, [95% CI:0 - 13.2%]). At delivery, two additional subjects had late gestation transmission. Considering all three cases with maternal-fetal transmission, the transmission rate was 7.5% of 40 cases, [95% CI: 1,6 - 20.4%]). All infected neonates were asymptomatic at birth. Matched historical controls were 108 pregnancies with 38 transmissions (35.2%, [95% CI: 26.2 - 45.0%]), which was significantly higher than in the HIG administration group. CONCLUSION After a primary maternal CMV infection in the first trimester, HIG administration prevents maternal-fetal transmission up to 20 weeks of gestation. This article is protected by copyright. All rights reserved.}, keywords = {}, pubstate = {published}, tppubtype = {article} } OBJECTIVE To examine the efficacy of biweekly hyperimmunoglobulin (HIG) administration to women with first trimester CMV infection for preventing maternal-fetal transmission of CMV. METHODS Subjects were 40 pregnant women with a primary CMV infection with a median gestational age at diagnosis of 9.6 weeks with a range of 5.1 to 14.3 weeks' gestation. On average, HIG administration started at 11.1 weeks and continued until 16.6 weeks' gestation. Within this interval, HIG was administered between 2 and 6 times. While CMV IgG monitoring showed periodic fluctuations during biweekly HIG administration cycles, high CMV IgG avidity indices remained stable over the whole treatment period. The results were compared with a historic cohort with first trimester CMV infection without treatment that also had an amniocentesis at about 20 weeks RESULTS: Each subject had amniocentesis performed. Maternal-fetal transmission before amniocentesis occurred in only one of the 40 cases (2.5%, [95% CI:0 - 13.2%]). At delivery, two additional subjects had late gestation transmission. Considering all three cases with maternal-fetal transmission, the transmission rate was 7.5% of 40 cases, [95% CI: 1,6 - 20.4%]). All infected neonates were asymptomatic at birth. Matched historical controls were 108 pregnancies with 38 transmissions (35.2%, [95% CI: 26.2 - 45.0%]), which was significantly higher than in the HIG administration group. CONCLUSION After a primary maternal CMV infection in the first trimester, HIG administration prevents maternal-fetal transmission up to 20 weeks of gestation. This article is protected by copyright. All rights reserved. |
Böttcher, S; Diedrich, S; Keeren, K Increased detection of enterovirus A71 infections, Germany, 2019 Artikel Eurosurveillance, 24 (39), S. 30005, 2019. @article{Bottcher.2019, title = {Increased detection of enterovirus A71 infections, Germany, 2019}, author = {S B\"{o}ttcher and S Diedrich and K Keeren}, doi = {10.2807/1560-7917.ES.2019.24.39.1900556}, year = {2019}, date = {2019-01-01}, journal = {Eurosurveillance}, volume = {24}, number = {39}, pages = {30005}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Exler, S; Daiminger, A; Grothe, M; Schalasta, G; Enders, G; Enders, M Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology, 117 , S. 33–36, 2019, ISSN: 1386-6532. @article{Exler.2019, title = {Primary cytomegalovirus (CMV) infection in pregnancy: Diagnostic value of CMV PCR in saliva compared to urine at birth}, author = {S Exler and A Daiminger and M Grothe and G Schalasta and G Enders and M Enders}, doi = {10.1016/j.jcv.2019.05.015}, issn = {1386-6532}, year = {2019}, date = {2019-01-01}, journal = {Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology}, volume = {117}, pages = {33--36}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Enders, M Zytomegalie, Ringelröteln und Co. - Pränatale Virus-Infektionen Artikel Gynäkologie + Geburtshilfe, 24 (3), S. 28–34, 2019, ISSN: 1439-3557. @article{Enders.2019, title = {Zytomegalie, Ringelr\"{o}teln und Co. - Pr\"{a}natale Virus-Infektionen}, author = {M Enders}, doi = {10.1007/s15013-019-1729-6}, issn = {1439-3557}, year = {2019}, date = {2019-01-01}, journal = {Gyn\"{a}kologie + Geburtshilfe}, volume = {24}, number = {3}, pages = {28--34}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Eggers, M Correction to: Infectious Disease Management and Control with Povidone Iodine Artikel Infectious diseases and therapy, 2019, ISSN: 2193-8229. @article{Eggers.2019b, title = {Correction to: Infectious Disease Management and Control with Povidone Iodine}, author = {M Eggers}, doi = {10.1007/s40121-019-00263-8}, issn = {2193-8229}, year = {2019}, date = {2019-01-01}, journal = {Infectious diseases and therapy}, abstract = {In the original publication, Figure~1 was incorrectly published. The correct figure is given here.}, keywords = {}, pubstate = {published}, tppubtype = {article} } In the original publication, Figure~1 was incorrectly published. The correct figure is given here. |
Eggers, M Infectious Disease Management and Control with Povidone Iodine Artikel Infectious diseases and therapy, 2019, ISSN: 2193-8229. @article{Eggers.2019, title = {Infectious Disease Management and Control with Povidone Iodine}, author = {M Eggers}, doi = {10.1007/s40121-019-00260-x}, issn = {2193-8229}, year = {2019}, date = {2019-01-01}, journal = {Infectious diseases and therapy}, abstract = {With reports of vancomycin-resistant enterococci recently emerging in hospital settings, renewed focus is turning to the importance of multifaceted infection prevention efforts. Careful compliance with established hygiene practices by healthcare workers together with effective antiseptic options is essential for the protection of patients from infectious agents. For over 60~years, povidone iodine (PVP-I) formulations have been shown to limit the impact and spread of infectious diseases with potent antiviral, antibacterial and antifungal effects. In addition to a lack of reported resistance, the benefits of PVP-I include an excellent safety profile and a broad spectrum of effect due to its multimodal action. Studies have shown that hand washing with PVP-I-based antiseptics is effective for the decontamination of skin, while PVP-I mouthwashes and gargles significantly reduce viral load in the oral cavity and the oropharynx. The importance of PVP-I has been emphasised by its inclusion in the World Health Organization's list of essential medicines, and high potency for virucidal activity has been observed against viruses of significant global concern, including hepatitis A and influenza, as well as the Middle-East Respiratory Syndrome and Sudden Acute Respiratory Syndrome coronaviruses. Together with its diverse applications in antimicrobial control, broad accessibility across the globe, and outstanding safety and tolerability profile, PVP-I offers an affordable, potent, and widely available antiseptic option.Funding Mundipharma Singapore Holding Pte Limited.}, keywords = {}, pubstate = {published}, tppubtype = {article} } With reports of vancomycin-resistant enterococci recently emerging in hospital settings, renewed focus is turning to the importance of multifaceted infection prevention efforts. Careful compliance with established hygiene practices by healthcare workers together with effective antiseptic options is essential for the protection of patients from infectious agents. For over 60~years, povidone iodine (PVP-I) formulations have been shown to limit the impact and spread of infectious diseases with potent antiviral, antibacterial and antifungal effects. In addition to a lack of reported resistance, the benefits of PVP-I include an excellent safety profile and a broad spectrum of effect due to its multimodal action. Studies have shown that hand washing with PVP-I-based antiseptics is effective for the decontamination of skin, while PVP-I mouthwashes and gargles significantly reduce viral load in the oral cavity and the oropharynx. The importance of PVP-I has been emphasised by its inclusion in the World Health Organization's list of essential medicines, and high potency for virucidal activity has been observed against viruses of significant global concern, including hepatitis A and influenza, as well as the Middle-East Respiratory Syndrome and Sudden Acute Respiratory Syndrome coronaviruses. Together with its diverse applications in antimicrobial control, broad accessibility across the globe, and outstanding safety and tolerability profile, PVP-I offers an affordable, potent, and widely available antiseptic option.Funding Mundipharma Singapore Holding Pte Limited. |
Kagan, K O; Maier, V; Sonek, J; Abele, H; Lüthgens, K; Schmid, M; Wagner, P; Hoopmann, M Fetal diagnosis and therapy, 45 (5), S. 317–324, 2019, ISSN: 1015-3837. @article{Kagan.2019, title = {False-Positive Rate in First-Trimester Screening Based on Ultrasound and Cell-Free DNA versus First-Trimester Combined Screening with Additional Ultrasound Markers}, author = {K O Kagan and V Maier and J Sonek and H Abele and K L\"{u}thgens and M Schmid and P Wagner and M Hoopmann}, doi = {10.1159/000489121}, issn = {1015-3837}, year = {2019}, date = {2019-01-01}, journal = {Fetal diagnosis and therapy}, volume = {45}, number = {5}, pages = {317--324}, abstract = {OBJECTIVE To determine whether screening for trisomy 21 based on first-trimester combined screening (FTCS) with assessment of nasal bone (NB), tricuspid flow (TCF), and ductus venosus flow (DVF) results in similar false-positive rates compared to ultrasound and cell-free DNA (cfDNA) screening. METHODS This is a subanalysis of a prospective randomized controlled trial which was performed between October 2015 and December 2016. Pregnant women with a normal first-trimester ultrasound examination at 11 to 13 weeks' gestation were randomized into two groups: (1) FTCS with assessment of the NB, TCF, and DVF (extended FTCS [eFTCS]), and (2) ultrasound + cfDNA screening. The false-positive rate in screening for trisomy 21 was defined as the primary outcome parameter. RESULTS The study population consisted of 688 women in each study arm. In the eFTCS group, the median delta fetal nuchal translucency thickness (NT) was 0.0 mm, free beta-hCG and PAPP-A were 0.96 and 1.11 MoM, and NB, TCF, and DVF PIV were abnormal in 0.9, 0.6, and 7.0% cases. In the ultrasound + cfDNA group, the median delta NT was 0.0 mm. In 10 pregnancies the cfDNA analysis was uninformative and the risk of trisomy 21 was based on eFTCS. There were no false-positive cases in the ultrasound + cfDNA group, whereas the false-positive rates were between 0.9 and 2.2% with eFTCS. CONCLUSION Screening for trisomy 21 based on ultrasound + cfDNA has a lower false-positive rate than screening based on eFTCS.}, keywords = {}, pubstate = {published}, tppubtype = {article} } OBJECTIVE To determine whether screening for trisomy 21 based on first-trimester combined screening (FTCS) with assessment of nasal bone (NB), tricuspid flow (TCF), and ductus venosus flow (DVF) results in similar false-positive rates compared to ultrasound and cell-free DNA (cfDNA) screening. METHODS This is a subanalysis of a prospective randomized controlled trial which was performed between October 2015 and December 2016. Pregnant women with a normal first-trimester ultrasound examination at 11 to 13 weeks' gestation were randomized into two groups: (1) FTCS with assessment of the NB, TCF, and DVF (extended FTCS [eFTCS]), and (2) ultrasound + cfDNA screening. The false-positive rate in screening for trisomy 21 was defined as the primary outcome parameter. RESULTS The study population consisted of 688 women in each study arm. In the eFTCS group, the median delta fetal nuchal translucency thickness (NT) was 0.0 mm, free beta-hCG and PAPP-A were 0.96 and 1.11 MoM, and NB, TCF, and DVF PIV were abnormal in 0.9, 0.6, and 7.0% cases. In the ultrasound + cfDNA group, the median delta NT was 0.0 mm. In 10 pregnancies the cfDNA analysis was uninformative and the risk of trisomy 21 was based on eFTCS. There were no false-positive cases in the ultrasound + cfDNA group, whereas the false-positive rates were between 0.9 and 2.2% with eFTCS. CONCLUSION Screening for trisomy 21 based on ultrasound + cfDNA has a lower false-positive rate than screening based on eFTCS. |
Gemein, S; Gebel, J; Christiansen, B; Martiny, H; Vossebein, L; Brill, F H H; Decius, M; Eggers, M; Koburger-Janssen, T; Meckel, M; Werner, S; Hunsinger, B; Selhorst, T; Kampf, G; Exner, M The Journal of hospital infection, 103 (1), S. 78–84, 2019. @article{Gemein.2019, title = {Interlaboratory reproducibility of a test method following 4-field test methodology to evaluate the susceptibility of Clostridium difficile spores}, author = {S Gemein and J Gebel and B Christiansen and H Martiny and L Vossebein and F H H Brill and M Decius and M Eggers and T Koburger-Janssen and M Meckel and S Werner and B Hunsinger and T Selhorst and G Kampf and M Exner}, doi = {10.1016/j.jhin.2019.04.011}, year = {2019}, date = {2019-01-01}, journal = {The Journal of hospital infection}, volume = {103}, number = {1}, pages = {78--84}, abstract = {BACKGROUND Sporicidal surface disinfection is recommended to control transmission of Clostridium difficile in healthcare facilities. EN 17126 provides a method to determine the sporicidal activity in suspension and has been approved as a European standard. In addition, a sporicidal surface test has been proposed. AIM To determine the interlaboratory reproducibility of a test method for evaluating the susceptibility of a C.~difficile spore preparation to a biocidal formulation following the 4-field test (EN 16615 methodology). METHODS Nine laboratories participated. C.~difficile NCTC 13366 spores were used. Glutaraldehyde (1% and 6%; 15 min) and peracetic acid (PAA; 0.01% and 0.04%; 15 min) were used to determine the spores' susceptibility in suspension in triplicate. FINDINGS One-percent glutaraldehyde revealed a mean decimal log10 reduction of 1.03 with variable results in the nine laboratories (0.37-1.49) and a reproducibility of 0.38. The effect of 6% glutaraldehyde was stronger (mean: 2.05; range: 0.96-4.29; reproducibility: 0.86). PAA revealed similar results. An exemplary biocidal formulation based on 5% PAA was used at 0.5% (non-effective concentration) and 4% (effective concentration) to determine the sporicidal efficacy (4-field test) under clean conditions in triplicate with a contact time of 15 min. When used at 0.5% it demonstrated an overall log10 reduction of 2.68 (range: 2.35-3.57) and at 4% of 4.61 (range: 3.82-5.71). The residual contamination on the three primarily uncontaminated test fields was textless50 cfu/25 cm2 in one out of nine laboratories (0.5%) and in seven out of nine laboratories (4%). CONCLUSION The interlaboratory reproducibility seems to be robust.}, keywords = {}, pubstate = {published}, tppubtype = {article} } BACKGROUND Sporicidal surface disinfection is recommended to control transmission of Clostridium difficile in healthcare facilities. EN 17126 provides a method to determine the sporicidal activity in suspension and has been approved as a European standard. In addition, a sporicidal surface test has been proposed. AIM To determine the interlaboratory reproducibility of a test method for evaluating the susceptibility of a C.~difficile spore preparation to a biocidal formulation following the 4-field test (EN 16615 methodology). METHODS Nine laboratories participated. C.~difficile NCTC 13366 spores were used. Glutaraldehyde (1% and 6%; 15 min) and peracetic acid (PAA; 0.01% and 0.04%; 15 min) were used to determine the spores' susceptibility in suspension in triplicate. FINDINGS One-percent glutaraldehyde revealed a mean decimal log10 reduction of 1.03 with variable results in the nine laboratories (0.37-1.49) and a reproducibility of 0.38. The effect of 6% glutaraldehyde was stronger (mean: 2.05; range: 0.96-4.29; reproducibility: 0.86). PAA revealed similar results. An exemplary biocidal formulation based on 5% PAA was used at 0.5% (non-effective concentration) and 4% (effective concentration) to determine the sporicidal efficacy (4-field test) under clean conditions in triplicate with a contact time of 15 min. When used at 0.5% it demonstrated an overall log10 reduction of 2.68 (range: 2.35-3.57) and at 4% of 4.61 (range: 3.82-5.71). The residual contamination on the three primarily uncontaminated test fields was textless50 cfu/25 cm2 in one out of nine laboratories (0.5%) and in seven out of nine laboratories (4%). CONCLUSION The interlaboratory reproducibility seems to be robust. |
2018 |
Spahr, C; Knauf-Witzens, T; Dahnert, L; Enders, M; Müller, M; Johne, R; Ulrich, R G Epidemiology and infection, 146 (1), S. 119–124, 2018, ISSN: 0950-2688. @article{Spahr.2018, title = {Detection of HEV-specific antibodies in four non-human primate species, including great apes, from different zoos in Germany}, author = {C Spahr and T Knauf-Witzens and L Dahnert and M Enders and M M\"{u}ller and R Johne and R G Ulrich}, doi = {10.1017/S0950268817002606}, issn = {0950-2688}, year = {2018}, date = {2018-01-01}, journal = {Epidemiology and infection}, volume = {146}, number = {1}, pages = {119--124}, abstract = {The hepatitis E virus (HEV) has been described in humans and various animal species in different regions of the world. However, the knowledge on natural HEV infection in non-human primates and the corresponding risk of zoonotic transmission is scarce. To determine whether primates in captivity are affected by HEV infection, we investigated 259 individual sera of clinically healthy non-human primates of 14 species from nine German zoos. Using a commercial double-antigen-sandwich ELISA and a commercial IgG ELISA, 10 animals (3.9%) reacted positive in at least one assay. Three ape species and one Old World monkey species were among the seropositive animals: bonobo (Pan paniscus), gorilla (Gorilla gorilla gorilla), lar gibbon (Hylobates lar) and drill (Mandrillus leucophaeus). Testing for anti-HEV-IgM antibodies by commercial ELISA and for viral RNA by reverse-transcription real-time polymerase chain reaction resulted in negative results for all animals indicating the absence of acute HEV infections. In the past, no clinical signs of hepatitis were recorded for the seropositive animals. The results suggest that non-human primates in zoos can get naturally and subclinically infected with HEV or related hepeviruses. Future studies should evaluate potential sources and transmission routes of these infections and their impact on human health}, keywords = {}, pubstate = {published}, tppubtype = {article} } The hepatitis E virus (HEV) has been described in humans and various animal species in different regions of the world. However, the knowledge on natural HEV infection in non-human primates and the corresponding risk of zoonotic transmission is scarce. To determine whether primates in captivity are affected by HEV infection, we investigated 259 individual sera of clinically healthy non-human primates of 14 species from nine German zoos. Using a commercial double-antigen-sandwich ELISA and a commercial IgG ELISA, 10 animals (3.9%) reacted positive in at least one assay. Three ape species and one Old World monkey species were among the seropositive animals: bonobo (Pan paniscus), gorilla (Gorilla gorilla gorilla), lar gibbon (Hylobates lar) and drill (Mandrillus leucophaeus). Testing for anti-HEV-IgM antibodies by commercial ELISA and for viral RNA by reverse-transcription real-time polymerase chain reaction resulted in negative results for all animals indicating the absence of acute HEV infections. In the past, no clinical signs of hepatitis were recorded for the seropositive animals. The results suggest that non-human primates in zoos can get naturally and subclinically infected with HEV or related hepeviruses. Future studies should evaluate potential sources and transmission routes of these infections and their impact on human health |
Schalasta, G; Börner, A; Speicher, A; Enders, M Clinical chemistry and laboratory medicine, 56 (4), S. 634–641, 2018, ISSN: 1434-6621. @article{Schalasta.2018, title = {Evaluation of the Aptima HBV Quant assay vs. the COBAS TaqMan HBV test using the high pure system for the quantitation of HBV DNA in plasma and serum samples}, author = {G Schalasta and A B\"{o}rner and A Speicher and M Enders}, doi = {10.1515/cclm-2017-0701}, issn = {1434-6621}, year = {2018}, date = {2018-01-01}, journal = {Clinical chemistry and laboratory medicine}, volume = {56}, number = {4}, pages = {634--641}, abstract = {BACKGROUND: Proper management of patients with chronic hepatitis B virus (HBV) infection requires monitoring of plasma or serum HBV DNA levels using a highly sensitive nucleic acid amplification test. Because commercially available assays differ in performance, we compared herein the performance of the Hologic Aptima HBV Quant assay (Aptima) to that of the Roche Cobas TaqMan HBV test for use with the high pure system (HPS/CTM). METHODS: Assay performance was assessed using HBV reference panels as well as plasma and serum samples from chronically HBV-infected patients. Method correlation, analytical sensitivity, precision/reproducibility, linearity, bias and influence of genotype were evaluated. Data analysis was performed using linear regression, Deming correlation analysis and Bland-Altman analysis. RESULTS: Agreement between the assays for the two reference panels was good, with a difference in assay values vs. target textless0.5 log. Qualitative assay results for 159 clinical samples showed good concordance (88.1%; kappa=0.75; 95% confidence interval: 0.651-0.845). For the 106 samples quantitated by both assays, viral load results were highly correlated (R=0.92) and differed on average by 0.09 log, with 95.3% of the samples being within the 95% limit of agreement of the assays. Linearity for viral loads 1-7 log was excellent for both assays (R2textgreater0.98). The two assays had similar bias and precision across the different genotypes tested at low viral loads (25-1000 IU/mL). CONCLUSIONS: Aptima has a performance comparable with that of HPS/CTM, making it suitable for use for HBV infection monitoring. Aptima runs on a fully automated platform (the Panther system) and therefore offers a significantly improved workflow compared with HPS/CTM}, keywords = {}, pubstate = {published}, tppubtype = {article} } BACKGROUND: Proper management of patients with chronic hepatitis B virus (HBV) infection requires monitoring of plasma or serum HBV DNA levels using a highly sensitive nucleic acid amplification test. Because commercially available assays differ in performance, we compared herein the performance of the Hologic Aptima HBV Quant assay (Aptima) to that of the Roche Cobas TaqMan HBV test for use with the high pure system (HPS/CTM). METHODS: Assay performance was assessed using HBV reference panels as well as plasma and serum samples from chronically HBV-infected patients. Method correlation, analytical sensitivity, precision/reproducibility, linearity, bias and influence of genotype were evaluated. Data analysis was performed using linear regression, Deming correlation analysis and Bland-Altman analysis. RESULTS: Agreement between the assays for the two reference panels was good, with a difference in assay values vs. target textless0.5 log. Qualitative assay results for 159 clinical samples showed good concordance (88.1%; kappa=0.75; 95% confidence interval: 0.651-0.845). For the 106 samples quantitated by both assays, viral load results were highly correlated (R=0.92) and differed on average by 0.09 log, with 95.3% of the samples being within the 95% limit of agreement of the assays. Linearity for viral loads 1-7 log was excellent for both assays (R2textgreater0.98). The two assays had similar bias and precision across the different genotypes tested at low viral loads (25-1000 IU/mL). CONCLUSIONS: Aptima has a performance comparable with that of HPS/CTM, making it suitable for use for HBV infection monitoring. Aptima runs on a fully automated platform (the Panther system) and therefore offers a significantly improved workflow compared with HPS/CTM |
Enders, M Ringelröteln in der Schwangerschaft: Frauenärzte im Netz Sonstige 2018. @misc{Enders.2018d, title = {Ringelr\"{o}teln in der Schwangerschaft: Frauen\"{a}rzte im Netz}, author = {M Enders}, url = {https://www.frauenaerzte-im-netz.de/erkrankungen/ringelroeteln-in-der-schwangerschaft/wichtige-hinweise/}, year = {2018}, date = {2018-01-01}, abstract = {Wichtige Hinweise zum Thema Ringelr\"{o}teln, wie z.B. bei Ringelr\"{o}teln im Umfeld sollte der Immunschutz der Schwangeren \"{u}berpr\"{u}ft werden. Dies ist eine Kassenleistung.}, keywords = {}, pubstate = {published}, tppubtype = {misc} } Wichtige Hinweise zum Thema Ringelröteln, wie z.B. bei Ringelröteln im Umfeld sollte der Immunschutz der Schwangeren überprüft werden. Dies ist eine Kassenleistung. |
Modrow, S; Buxmann, H; Enders, M; Gembruch, U; Goelz, R; Hamprecht, K; Huzly, D; Kummer, P; Kagan, K O; Knuf, M; Mertens, T; Nennstiel-Ratzel, U; Roll, C; Wojcinski, M Management der kongenitalen Zytomegalievirus-Infektion bei Neugeborenen Artikel Kinder- und Jugendarzt, 49 (3), S. 107–117, 2018, ISSN: 1436-9559. @article{Modrow.2018b, title = {Management der kongenitalen Zytomegalievirus-Infektion bei Neugeborenen}, author = {S Modrow and H Buxmann and M Enders and U Gembruch and R Goelz and K Hamprecht and D Huzly and P Kummer and K O Kagan and M Knuf and T Mertens and U Nennstiel-Ratzel and C Roll and M Wojcinski}, issn = {1436-9559}, year = {2018}, date = {2018-01-01}, journal = {Kinder- und Jugendarzt}, volume = {49}, number = {3}, pages = {107--117}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Kagan, K O; Enders, M; Hoopmann, M; Hamprecht, K Behandlungsoptionen bei einer vorgeburtlichen CMV-Primärinfektion Artikel Frauenarzt, 59 (11), S. 854–858, 2018, ISSN: 0016-0237. @article{Kagan.2018b, title = {Behandlungsoptionen bei einer vorgeburtlichen CMV-Prim\"{a}rinfektion}, author = {K O Kagan and M Enders and M Hoopmann and K Hamprecht}, issn = {0016-0237}, year = {2018}, date = {2018-01-01}, journal = {Frauenarzt}, volume = {59}, number = {11}, pages = {854--858}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Chiaie, Delle L; Neuberger, P; Vochem, M; Lihs, A; Karck, U; Enders, M Archives of gynecology and obstetrics, 297 (6), S. 1389–1395, 2018, ISSN: 0932-0067. @article{DelleChiaie.2018, title = {No evidence of obstetrical adverse events after hyperimmune globulin application for primary cytomegalovirus infection in pregnancy: experience from a single centre}, author = {L Delle Chiaie and P Neuberger and M Vochem and A Lihs and U Karck and M Enders}, doi = {10.1007/s00404-018-4703-y}, issn = {0932-0067}, year = {2018}, date = {2018-01-01}, journal = {Archives of gynecology and obstetrics}, volume = {297}, number = {6}, pages = {1389--1395}, abstract = {PURPOSE: To determine the frequency of obstetrical adverse events and clinical outcome in infants following antenatal hyperimmune globulin (HIG) treatment for primary cytomegalovirus (CMV) infection in pregnancy. METHODS: Data from 50 women including three twin pregnancies were retrospectively evaluated. Primary infection was defined by seroconversion or the presence of CMV-specific IgM and low IgG avidity. All women received two or more infusions of HIG (200 U/kg). Congenital CMV (cCMV) infection was diagnosed by detection of CMV in amniotic fluid and/or neonatal urine. We compared gestational age (GA) at birth, head circumference (HC) and birth weight (BW) of infants in our study cohort with those of live-born infants delivered in our clinic between 2015 and 2016. RESULTS: Median gestational age at time of maternal CMV diagnosis was 13 weeks. One-hundred-forty-one maternal HIG doses were given. No HIG-related severe adverse reactions occurred. Preterm birth rate was 4.2% (2/47) in singleton pregnancies. None of the neonates had birth weight or head circumference textless 3rd percentile (textless 3P) for gestational age. There was no statistically significant difference regarding GA, BW and HC between our study cohort and the total population of live-born infants. The frequency of CMV-related sequelae in infants with cCMV infection was 10.5% (2/19) (one with bilateral hearing loss and one with mild motoric delay), both cases following first trimester maternal infection. CONCLUSION: Antenatal HIG treatment was well tolerated and not associated with prematurity or decreased birth weight. HIG application might have a favorable effect on the clinical course of congenital CMV infection}, keywords = {}, pubstate = {published}, tppubtype = {article} } PURPOSE: To determine the frequency of obstetrical adverse events and clinical outcome in infants following antenatal hyperimmune globulin (HIG) treatment for primary cytomegalovirus (CMV) infection in pregnancy. METHODS: Data from 50 women including three twin pregnancies were retrospectively evaluated. Primary infection was defined by seroconversion or the presence of CMV-specific IgM and low IgG avidity. All women received two or more infusions of HIG (200 U/kg). Congenital CMV (cCMV) infection was diagnosed by detection of CMV in amniotic fluid and/or neonatal urine. We compared gestational age (GA) at birth, head circumference (HC) and birth weight (BW) of infants in our study cohort with those of live-born infants delivered in our clinic between 2015 and 2016. RESULTS: Median gestational age at time of maternal CMV diagnosis was 13 weeks. One-hundred-forty-one maternal HIG doses were given. No HIG-related severe adverse reactions occurred. Preterm birth rate was 4.2% (2/47) in singleton pregnancies. None of the neonates had birth weight or head circumference textless 3rd percentile (textless 3P) for gestational age. There was no statistically significant difference regarding GA, BW and HC between our study cohort and the total population of live-born infants. The frequency of CMV-related sequelae in infants with cCMV infection was 10.5% (2/19) (one with bilateral hearing loss and one with mild motoric delay), both cases following first trimester maternal infection. CONCLUSION: Antenatal HIG treatment was well tolerated and not associated with prematurity or decreased birth weight. HIG application might have a favorable effect on the clinical course of congenital CMV infection |
Modrow, S; Buxmann, H; Enders, M; Gembruch, U; Goelz, R; Hamprecht, K; Huzly, D; Kummer, P; Kagan, K O; Knuf, M; Mertens, T; Nennstiel-Ratzel, U; Roll, C; Wojcinski, M Management der kongenitalen Zytomegalievirus-Infektion bei Neugeborenen Artikel Frauenarzt, 59 (5), S. 394–402, 2018, ISSN: 0016-0237. @article{Modrow.2018, title = {Management der kongenitalen Zytomegalievirus-Infektion bei Neugeborenen}, author = {S Modrow and H Buxmann and M Enders and U Gembruch and R Goelz and K Hamprecht and D Huzly and P Kummer and K O Kagan and M Knuf and T Mertens and U Nennstiel-Ratzel and C Roll and M Wojcinski}, issn = {0016-0237}, year = {2018}, date = {2018-01-01}, journal = {Frauenarzt}, volume = {59}, number = {5}, pages = {394--402}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Enders, M Zytomegalie in der Schwangerschaft: Frauenärzte im Netz Sonstige 2018. @misc{Enders.2018c, title = {Zytomegalie in der Schwangerschaft: Frauen\"{a}rzte im Netz}, author = {M Enders}, url = {https://www.frauenaerzte-im-netz.de/erkrankungen/zytomegalie-in-der-schwangerschaft/#c856}, year = {2018}, date = {2018-01-01}, abstract = {Die Zytomegalie (Cytomegalie) ist eine Infektionserkrankung, die durch das Cytomegalievirus (abgek\"{u}rzt CMV) verursacht wird. Bei Schwangeren kann das Virus auf das ungeborene Kind \"{u}bertragen werden (kongenitale CMV-Infektion) und dort zu schweren Sch\"{a}digungen f\"{u}hren.}, keywords = {}, pubstate = {published}, tppubtype = {misc} } Die Zytomegalie (Cytomegalie) ist eine Infektionserkrankung, die durch das Cytomegalievirus (abgekürzt CMV) verursacht wird. Bei Schwangeren kann das Virus auf das ungeborene Kind übertragen werden (kongenitale CMV-Infektion) und dort zu schweren Schädigungen führen. |
Geipel, A; Enders, M Geburtshilfe und Frauenheilkunde, 78 (06), S. 555–560, 2018, ISSN: 0016-5751. @article{Geipel.2018, title = {241. Stellungnahme der Deutschen Gesellschaft f\"{u}r Gyn\"{a}kologie und Geburtshilfe (DGGG) zum Thema Zikavirus-Infektion w\"{a}hrend der Schwangerschaft, Auswirkungen auf den Feten und Empfehlungen zur \"{U}berwachung und Diagnostik}, author = {A Geipel and M Enders}, doi = {10.1055/a-0607-5411}, issn = {0016-5751}, year = {2018}, date = {2018-01-01}, journal = {Geburtshilfe und Frauenheilkunde}, volume = {78}, number = {06}, pages = {555--560}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Enders, M Röteln in der Schwangerschaft: Frauenärzte im Netz Sonstige 2018. @misc{Enders.2018b, title = {R\"{o}teln in der Schwangerschaft: Frauen\"{a}rzte im Netz}, author = {M Enders}, url = {https://www.frauenaerzte-im-netz.de/erkrankungen/roeteln-in-der-schwangerschaft/#c724}, year = {2018}, date = {2018-01-01}, abstract = {R\"{o}teln geh\"{o}ren zu den am meisten gef\"{u}rchteten Infektionen in der Schwangerschaft, da sie beim Embryo zu schweren Akut- und Folgesch\"{a}den (R\"{o}telnembryopathie) f\"{u}hren k\"{o}nnen. Zwar ist in Deutschland seit Jahren keine R\"{o}telnembryopathie mehr gemeldet worden, aber die Infektion kann aus anderen, auch europ\"{a}ischen Regionen nach Deutschland eingeschleppt werden. Aufgrund von Impfl\"{u}cken (haupts\"{a}chlich bei Jugendlichen und jungen Erwachsenen) muss deshalb auch weiterhin mit R\"{o}teln in der Schwangerschaft und R\"{o}telnembryopathien gerechnet werden.}, keywords = {}, pubstate = {published}, tppubtype = {misc} } Röteln gehören zu den am meisten gefürchteten Infektionen in der Schwangerschaft, da sie beim Embryo zu schweren Akut- und Folgeschäden (Rötelnembryopathie) führen können. Zwar ist in Deutschland seit Jahren keine Rötelnembryopathie mehr gemeldet worden, aber die Infektion kann aus anderen, auch europäischen Regionen nach Deutschland eingeschleppt werden. Aufgrund von Impflücken (hauptsächlich bei Jugendlichen und jungen Erwachsenen) muss deshalb auch weiterhin mit Röteln in der Schwangerschaft und Rötelnembryopathien gerechnet werden. |
Härtel, C; Bialek, R; Enders, M; Gille, C; Handrick, W Syphilis Buchkapitel mit eigenem Titel Bialek, Ralf; Berner, Reinhard; Forster, Johannes; Härtel, Christoph; Heininger, Ulrich; Huppertz, Hans-Iko; Liese, Johannes G; Nadal, David; Simon, Arne (Hrsg.): DGPI-Handbuch, S. 764–769, Thieme, Stuttgart, 2018, ISBN: 978-3-13-240790-9. @incollection{Hartel.2018, title = {Syphilis}, author = {C H\"{a}rtel and R Bialek and M Enders and C Gille and W Handrick}, editor = {Ralf Bialek and Reinhard Berner and Johannes Forster and Christoph H\"{a}rtel and Ulrich Heininger and Hans-Iko Huppertz and Johannes G Liese and David Nadal and Arne Simon}, isbn = {978-3-13-240790-9}, year = {2018}, date = {2018-01-01}, booktitle = {DGPI-Handbuch}, pages = {764--769}, publisher = {Thieme}, address = {Stuttgart}, keywords = {}, pubstate = {published}, tppubtype = {incollection} } |
Enders, G; Enders, M; Steller, J Infektionen in der Schwangerschaft Buchkapitel mit eigenem Titel Goerke, Kay; Steller, Joachim; Valet, Axel; Dormann, Arno; Axt-Fliedner, Roland (Hrsg.): Klinikleitfaden Gynäkologie, Geburtshilfe, S. 185–231, Elsevier Urban & Fischer, München, 2018, ISBN: 978-3-437-22205-4. @incollection{Enders.2018, title = {Infektionen in der Schwangerschaft}, author = {G Enders and M Enders and J Steller}, editor = {Kay Goerke and Joachim Steller and Axel Valet and Arno Dormann and Roland Axt-Fliedner}, isbn = {978-3-437-22205-4}, year = {2018}, date = {2018-01-01}, booktitle = {Klinikleitfaden Gyn\"{a}kologie, Geburtshilfe}, pages = {185--231}, publisher = {Elsevier Urban & Fischer}, address = {M\"{u}nchen}, keywords = {}, pubstate = {published}, tppubtype = {incollection} } |
Wiesmann, F; Ehret, R; Naeth, G; Däumer, M; Fuhrmann, J; Kaiser, R; Noah, C; Obermeier, M; Schalasta, G; Tiemann, C; Wolf, E; Knechten, H; Braun, P Journal of clinical microbiology, 56 (10), 2018, ISSN: 0095-1137. @article{Wiesmann.2018, title = {Multicenter Evaluation of Two Next-Generation HIV-1 Quantitation Assays, Aptima Quant Dx and Cobas 6800, in Comparison to the RealTime HIV-1 Reference Assay}, author = {F Wiesmann and R Ehret and G Naeth and M D\"{a}umer and J Fuhrmann and R Kaiser and C Noah and M Obermeier and G Schalasta and C Tiemann and E Wolf and H Knechten and P Braun}, doi = {10.1128/JCM.00292-18}, issn = {0095-1137}, year = {2018}, date = {2018-01-01}, journal = {Journal of clinical microbiology}, volume = {56}, number = {10}, abstract = {High accuracy and precision at the lower end of quantification are crucial requirements of a modern HIV viral load (VL) assay, since some clinically relevant thresholds are located at 50 and 200 copies/ml. In this study, we compared the performance of two new fully automated HIV-1 VL assays, Aptima HIV-1 Quant Dx and Cobas HIV-1 (Cobas 6800), with the established RealTime m2000 assay. Assay precision and accuracy were evaluated in a retrospective evaluation out of excess plasma material from four HIV-1+ individuals (subtypes B, C, CRF01_AE, and CRF02_AG). Native plasma samples were diluted to nominal concentrations at 50 and 200 copies/ml (according to the RealTime m2000 assay). All dilutions were tested in triplicate in five independent runs over 5 days and in three labs per system. Assay concordance was determined using 1,011 surplus clinical routine samples, as well as selected retrospective longitudinal samples from 7 patients on treatment. The three assays yielded highly concordant results for individual clinical samples (R2 textgreater 0.98; average difference, $\leq$0.2 log copies/ml) and retrospective longitudinal samples from patients on treatment. The Aptima and RealTime assays showed similar high precision, meeting the 5textgreeks criterion for the majority of samples across all labs and subtypes. The Cobas assay was less precise, missing the 5textgreeks criterion for the majority of samples at low concentrations. In this analysis, results from the Cobas assay appeared less reliable near the clinically relevant cutoff and should be interpreted with more caution in this context. Due to high precision, full automation, and high concordance with the RealTime assay, the Aptima assay represents a good alternative in routine VL monitoring.}, keywords = {}, pubstate = {published}, tppubtype = {article} } High accuracy and precision at the lower end of quantification are crucial requirements of a modern HIV viral load (VL) assay, since some clinically relevant thresholds are located at 50 and 200 copies/ml. In this study, we compared the performance of two new fully automated HIV-1 VL assays, Aptima HIV-1 Quant Dx and Cobas HIV-1 (Cobas 6800), with the established RealTime m2000 assay. Assay precision and accuracy were evaluated in a retrospective evaluation out of excess plasma material from four HIV-1+ individuals (subtypes B, C, CRF01_AE, and CRF02_AG). Native plasma samples were diluted to nominal concentrations at 50 and 200 copies/ml (according to the RealTime m2000 assay). All dilutions were tested in triplicate in five independent runs over 5 days and in three labs per system. Assay concordance was determined using 1,011 surplus clinical routine samples, as well as selected retrospective longitudinal samples from 7 patients on treatment. The three assays yielded highly concordant results for individual clinical samples (R2 textgreater 0.98; average difference, $łeq$0.2 log copies/ml) and retrospective longitudinal samples from patients on treatment. The Aptima and RealTime assays showed similar high precision, meeting the 5textgreeks criterion for the majority of samples across all labs and subtypes. The Cobas assay was less precise, missing the 5textgreeks criterion for the majority of samples at low concentrations. In this analysis, results from the Cobas assay appeared less reliable near the clinically relevant cutoff and should be interpreted with more caution in this context. Due to high precision, full automation, and high concordance with the RealTime assay, the Aptima assay represents a good alternative in routine VL monitoring. |
Rauch, S; Doescher, A; Bald, R D blocking phenomenon overcome Artikel Transfusion, 58 (6), S. 1338–1339, 2018. @article{Rauch.2018, title = {D blocking phenomenon overcome}, author = {S Rauch and A Doescher and R Bald}, doi = {10.1111/trf.14496}, year = {2018}, date = {2018-01-01}, journal = {Transfusion}, volume = {58}, number = {6}, pages = {1338--1339}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Kagan, K O; Sroka, F; Sonek, J; Abele, H; Lüthgens, K; Schmid, M; Wagner, P; Brucker, S; Wallwiener, D; Hoopmann, M Ultrasound in obstetrics & gynecology, 51 (4), S. 437–444, 2018, ISSN: 0960-7692. @article{Kagan.2018, title = {First-trimester risk assessment based on ultrasound and cell-free DNA vs combined screening: a randomized controlled trial}, author = {K O Kagan and F Sroka and J Sonek and H Abele and K L\"{u}thgens and M Schmid and P Wagner and S Brucker and D Wallwiener and M Hoopmann}, doi = {10.1002/uog.18905}, issn = {0960-7692}, year = {2018}, date = {2018-01-01}, journal = {Ultrasound in obstetrics & gynecology}, volume = {51}, number = {4}, pages = {437--444}, abstract = {OBJECTIVE This was a randomized controlled trial to compare risk assessment by first-trimester combined screening (FTCS) with an approach that combines a detailed ultrasound examination at 11-13 weeks' gestation and cell-free DNA (cfDNA) analysis. METHODS Pregnant women with a normal first-trimester ultrasound examination at 11-13 weeks' gestation (fetal nuchal translucency (NT)~$\leq$ 3.5 mm and no fetal defects) were randomized into one of two groups. In the first group, risk of aneuploidy was assessed using FTCS based on the most recent UK Fetal Medicine Foundation algorithm. In the second group, risk assessment was based on ultrasound findings and cfDNA analysis. An additional tube of blood was collected for FTCS in case the cfDNA analysis was uninformative. Primary outcome was false-positive rate in screening for trisomy 21. A case was considered false positive if the karyotype was not trisomy 21 and if the risk for trisomy 21 was textgreater1:100, irrespective of the method of risk calculation. Results were compared using 95% CIs using the Clopper-Pearson method. RESULTS Between October 2015 and December 2016, 1518 women with singleton pregnancy underwent first-trimester screening. Thirty-one (2.0%) pregnancies were not eligible for randomization due to increased NT (textgreater 3.5 mm) and/or fetal defect. After exclusion of women who declined randomization (n~= 87) and cases of fetal death and loss to follow-up (n~= 24), 688 pregnancies were randomized into the FTCS arm and 688 into the ultrasound + cfDNA analysis arm. There were no differences in maternal and gestational age, maternal weight and BMI, ethnicity, use of assisted reproduction and cigarette smoking between the two arms. In the ultrasound + cfDNA analysis arm, median risk for trisomy 21 was 1 in 10 000. None of the cases had a risk above 1: 100 (95% CI, 0.0-0.5%). In the FTCS arm, the median risk for trisomy 21 was 1 in 3787 and in 17 cases, the risk was higher than 1:100, which corresponds to 2.5% (95% CI, 1.5-3.9%) of the FTCS study-arm population. CONCLUSION Our study has shown that first-trimester risk assessment for trisomy 21 that includes a detailed ultrasound examination as well as NT measurement and is followed by cfDNA testing is associated with a significant reduction in the false-positive rate compared with FTCS. This approach obviates the need for maternal serum free textgreekb-human chorionic gonadotropin and pregnancy-associated plasma protein-A in screening for fetal aneuploidy. Copyright copyright 2017 ISUOG. Published by John Wiley & Sons Ltd.}, keywords = {}, pubstate = {published}, tppubtype = {article} } OBJECTIVE This was a randomized controlled trial to compare risk assessment by first-trimester combined screening (FTCS) with an approach that combines a detailed ultrasound examination at 11-13 weeks' gestation and cell-free DNA (cfDNA) analysis. METHODS Pregnant women with a normal first-trimester ultrasound examination at 11-13 weeks' gestation (fetal nuchal translucency (NT)~$łeq$ 3.5 mm and no fetal defects) were randomized into one of two groups. In the first group, risk of aneuploidy was assessed using FTCS based on the most recent UK Fetal Medicine Foundation algorithm. In the second group, risk assessment was based on ultrasound findings and cfDNA analysis. An additional tube of blood was collected for FTCS in case the cfDNA analysis was uninformative. Primary outcome was false-positive rate in screening for trisomy 21. A case was considered false positive if the karyotype was not trisomy 21 and if the risk for trisomy 21 was textgreater1:100, irrespective of the method of risk calculation. Results were compared using 95% CIs using the Clopper-Pearson method. RESULTS Between October 2015 and December 2016, 1518 women with singleton pregnancy underwent first-trimester screening. Thirty-one (2.0%) pregnancies were not eligible for randomization due to increased NT (textgreater 3.5 mm) and/or fetal defect. After exclusion of women who declined randomization (n~= 87) and cases of fetal death and loss to follow-up (n~= 24), 688 pregnancies were randomized into the FTCS arm and 688 into the ultrasound + cfDNA analysis arm. There were no differences in maternal and gestational age, maternal weight and BMI, ethnicity, use of assisted reproduction and cigarette smoking between the two arms. In the ultrasound + cfDNA analysis arm, median risk for trisomy 21 was 1 in 10 000. None of the cases had a risk above 1: 100 (95% CI, 0.0-0.5%). In the FTCS arm, the median risk for trisomy 21 was 1 in 3787 and in 17 cases, the risk was higher than 1:100, which corresponds to 2.5% (95% CI, 1.5-3.9%) of the FTCS study-arm population. CONCLUSION Our study has shown that first-trimester risk assessment for trisomy 21 that includes a detailed ultrasound examination as well as NT measurement and is followed by cfDNA testing is associated with a significant reduction in the false-positive rate compared with FTCS. This approach obviates the need for maternal serum free textgreekb-human chorionic gonadotropin and pregnancy-associated plasma protein-A in screening for fetal aneuploidy. Copyright copyright 2017 ISUOG. Published by John Wiley & Sons Ltd. |
