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Article: Susceptibility, Immunity, and Persistent Infection Drive Endemic Cycles of Coxiellosis on Dairy Farms.

Böttcher, Jens / Alex, Michaela / Dänicke, Sven / Gethmann, Jörn / Mertens-Scholz, Katja / Janowetz, Britta

Animals : an open access journal from MDPI

2024 Volume 14, Issue 7

Abstract: Coxiella (C.) ... ...

Abstract	Coxiella (C.) burnetii
Language	English
Publishing date	2024-03-29
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2606558-7
ISSN	2076-2615
ISSN	2076-2615
DOI	10.3390/ani14071056
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: An intercomparison study of ELISAs for the detection of porcine reproductive and respiratory syndrome virus - evaluating six conditionally dependent tests.

Schoneberg, Clara / Böttcher, Jens / Janowetz, Britta / Rostalski, Anja / Kreienbrock, Lothar / Campe, Amely

PloS one

2022 Volume 17, Issue 1, Page(s) e0262944

Abstract: Latent class analysis is a widely used statistical method for evaluating diagnostic tests without any gold standard. It requires the results of at least two tests applied to the same individuals. Based on the resulting response patterns, the method ... ...

Abstract	Latent class analysis is a widely used statistical method for evaluating diagnostic tests without any gold standard. It requires the results of at least two tests applied to the same individuals. Based on the resulting response patterns, the method estimates the test accuracy and the unknown disease status for all individuals in the sample. An important assumption is the conditional independence of the tests. If tests with the same biological principle are used, the assumption is not fulfilled, which may lead to biased results. In a recent publication, we developed a method that considers the dependencies in the latent class model and estimates all parameters using frequentist methods. Here, we evaluate the practicability of the method by applying it to the results of six ELISA tests for antibodies against the porcine reproductive and respiratory syndrome (PRRS) virus in pigs that generally follow the same biological principle. First, we present different methods of identifying suitable starting values for the algorithm and apply these to the dataset and a vaccinated subgroup. We present the calculated values of the test accuracies, the estimated proportion of antibody-positive animals and the dependency structure for both datasets. Different starting values led to matching results for the entire dataset. For the vaccinated subgroup, the results were more dependent on the selected starting values. All six ELISA tests are well suited to detect antibodies against PRRS virus, whereas none of the tests had the best values for sensitivity and specificity simultaneously. The results thus show that the method used is able to determine the parameter values of conditionally dependent tests with suitable starting values. The choice of test should be based on the general fit-for-purpose concept and the population under study.
MeSH term(s)	Animals ; Antibodies, Viral/blood ; Enzyme-Linked Immunosorbent Assay ; Female ; Male ; Porcine Reproductive and Respiratory Syndrome/blood ; Porcine Reproductive and Respiratory Syndrome/virology ; Porcine respiratory and reproductive syndrome virus/metabolism ; Swine
Chemical Substances	Antibodies, Viral
Language	English
Publishing date	2022-01-25
Publishing country	United States
Document type	Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0262944
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: The immune response to a Coxiella burnetii vaccine in sheep varies according to their natural pre-exposure.

Böttcher, Jens / Bauer, Benjamin U / Ambros, Christina / Alex, Michaela / Domes, Ursula / Roth, Sabine / Boll, Kerstin / Korneli, Martin / Bogner, Karl-Heinz / Randt, Andreas / Janowetz, Britta

Vaccine

2024 Volume 42, Issue 8, Page(s) 1993–2003

Abstract: Q fever in humans is caused by Coxiella (C.) burnetii. In 2008 and 2012, cases of Q fever in humans were linked to an infected flock of approximately 650 ewes. Since 2013 gimmers (G'13, G'14, G'15 etc.) were primary vaccinated (two doses) with an ... ...

Abstract	Q fever in humans is caused by Coxiella (C.) burnetii. In 2008 and 2012, cases of Q fever in humans were linked to an infected flock of approximately 650 ewes. Since 2013 gimmers (G'13, G'14, G'15 etc.) were primary vaccinated (two doses) with an inactivated C.burnetii vaccine without any revaccination. In 2013, 30 ewes were primary vaccinated (A'13). Shedding was annually monitored by qPCR-testing of vaginal and nasal swabs collected at lambing. Animals were tested for Phase I- (PhI) and PhII-antibodies (Ab) and for PhII-specific-interferon-γ (IFN-γ) before and after vaccination. The effect of a revaccination was determined in 2018 and 2023. Groups of randomly selected gimmers primary vaccinated in 2015, 2016 and 2017 and a mixed group of older animals (A'13, G'13 and G'14) were revaccinated once in 2018. The trial was repeated in 2023 on groups primary vaccinated in 2019-2023. Major shedding after the outbreak in 2012 ceased in 2014. Thereafter C.burnetii was only sporadically detected at low-level in 2018, 2021 and 2023. Sheep naturally exposed to C.burnetii during the outbreak in 2012 (A'13, G'13) mounted a strong and complete (PhI, PhII, IFN-γ) recall immune response after vaccination. A serological PhI
MeSH term(s)	Humans ; Sheep ; Animals ; Female ; Coxiella burnetii ; Q Fever/prevention & control ; Q Fever/veterinary ; Q Fever/epidemiology ; Antibodies ; Bacterial Vaccines ; Immunity
Chemical Substances	Antibodies ; Bacterial Vaccines
Language	English
Publishing date	2024-02-21
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	605674-x
ISSN	1873-2518 ; 0264-410X
ISSN (online)	1873-2518
ISSN	0264-410X
DOI	10.1016/j.vaccine.2024.02.048
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Article: Long-term control of Coxiellosis in sheep by annual primary vaccination of gimmers

Böttcher, Jens / Bauer, Benjamin U. / Ambros, Christina / Alex, Michaela / Domes, Ursula / Roth, Sabine / Boll, Kerstin / Korneli, Martin / Bogner, Karl-Heinz / Randt, Andreas / Janowetz, Britta

Vaccine. 2022 July 21,

2022

Abstract: Coxiella (C.) burnetii, a Gram-negative intracellular bacterium, causes Q fever in humans and Coxiellosis in animals. Ruminants are a primary source of human infection with C.burnetii. In 2013, vaccination was implemented in a sheep flock with 650 ewes ... ...

Abstract	Coxiella (C.) burnetii, a Gram-negative intracellular bacterium, causes Q fever in humans and Coxiellosis in animals. Ruminants are a primary source of human infection with C.burnetii. In 2013, vaccination was implemented in a sheep flock with 650 ewes associated with two outbreaks of Q fever in humans in 2008 and 2012. Only gimmers (yearlings) received two doses of a commercial C.burnetii phase I whole cell vaccine three weeks apart (primary vaccination) without any revaccination. Vaginal and nasal swabs collected shortly after lambing were tested by qPCR. Additionally, a group of non-vaccinated sentinels was serologically monitored for phase I (PhI), II (PhII) antibodies and for Interferon γ (IFN-γ) after stimulation of whole blood cells with PhII-antigen with and without an IL-10-neutralizing monoclonal antibody. In 2021, 679 sera collected in 2014–2021 were retested retrospectively with three commercial ELISA kits and one batch of an in-house PhI/PhII-ELISA. A low-level shedding of C.burnetii (<10³ mean C.burnetii/swab) was observed until 2014. In 2021 C.burnetii was detected in two animals (<10³.¹C.burnetii/swab), but vaginal swabs collected at two subsequent lambing seasons remained negative. Seroconversion of sentinels was detected until 2017. However, the retrospective analysis of sentinels in 2021 revealed additional single seropositive animals from 2018 to 2021. IFN-γ reactivity was observed during the whole study period; it peaked in 2014 and in 2018 and decreased thereafter. The sporadic detection of C.burnetii and the immune responses of sentinels suggested that a subliminal infection persisted despite vaccination. Nevertheless, vaccination of gimmers prevented the development of a major outbreak, it controlled the infection and reduced the risk of human infection.
Keywords	Coxiella ; Q fever ; bacteria ; flocks ; human diseases ; monoclonal antibodies ; nose ; retrospective studies ; seroconversion ; seroprevalence ; vaccination ; vaccines
Language	English
Dates of publication	2022-0721
Publishing place	Elsevier Ltd
Document type	Article
Note	Pre-press version
ZDB-ID	605674-x
ISSN	1873-2518 ; 0264-410X
ISSN (online)	1873-2518
ISSN	0264-410X
DOI	10.1016/j.vaccine.2022.07.029
Database	NAL-Catalogue (AGRICOLA)

In stock of ZB MED Cologne/Königswinter

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Article: Isolation and Cultivation of a New Isolate of BTV-25 and Presumptive Evidence for a Potential Persistent Infection in Healthy Goats

Ries, Christina / Domes, Ursula / Janowetz, Britta / Böttcher, Jens / Burkhardt, Katinka / Miller, Thomas / Beer, Martin / Hoffmann, Bernd

Viruses. 2020 Sept. 04, v. 12, no. 9

2020

Abstract: Recently, several so-called “atypical” Bluetongue virus (BTV) serotypes were discovered, including BTV-25 (Toggenburg virus), in Switzerland. Most “atypical” BTV were identified in small ruminants without clinical signs. In 2018, two goats from a holding ...

Abstract	Recently, several so-called “atypical” Bluetongue virus (BTV) serotypes were discovered, including BTV-25 (Toggenburg virus), in Switzerland. Most “atypical” BTV were identified in small ruminants without clinical signs. In 2018, two goats from a holding in Germany tested positive for BTV-25 genome by RT-qPCR prior to export. After experimental inoculation of the two goats with the BTV-25 positive field blood samples for generation of reference materials, viremia could be observed in one animal. For the first time, the BTV-25-related virus was isolated in cell culture from EDTA-blood and the full genome of isolate “BTV-25-GER2018” could be generated. BTV-25-GER2018 was only incompletely neutralized by ELISA-positive sera. We could monitor the BTV-25 occurrence in the respective affected goat flock of approximately 120 goats over several years. EDTA blood samples were screened with RT-qPCR using a newly developed BTV-25 specific assay. For serological surveillance, serum samples were screened using a commercial cELISA. BTV-25-GER2018 was detected over 4.5 years in the goat flock with intermittent PCR-positivity in some animals, and with or without concomitantly detected antibodies since 2015. We could demonstrate the viral persistence of BTV-25-GER2018 in goats for up to 4.5 years, and the first BTV-25 isolate is now available for further characterization.
Keywords	Bluetongue virus ; EDTA (chelating agent) ; Toggenburg ; antibodies ; blood sampling ; blood serum ; cell culture ; chronic diseases ; enzyme-linked immunosorbent assay ; exports ; flocks ; genome ; goat diseases ; goats ; monitoring ; neutralization ; quantitative polymerase chain reaction ; reverse transcriptase polymerase chain reaction ; serotypes ; signs and symptoms (animals and humans) ; viremia ; viruses ; Germany ; Switzerland
Language	English
Dates of publication	2020-0904
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article
ZDB-ID	2516098-9
ISSN	1999-4915
ISSN	1999-4915
DOI	10.3390/v12090983
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Long-term control of Coxiellosis in sheep by annual primary vaccination of gimmers.

Böttcher, Jens / Bauer, Benjamin U / Ambros, Christina / Alex, Michaela / Domes, Ursula / Roth, Sabine / Boll, Kerstin / Korneli, Martin / Bogner, Karl-Heinz / Randt, Andreas / Janowetz, Britta

Vaccine

2022 Volume 40, Issue 35, Page(s) 5197–5206

Abstract	Coxiella (C.) burnetii, a Gram-negative intracellular bacterium, causes Q fever in humans and Coxiellosis in animals. Ruminants are a primary source of human infection with C.burnetii. In 2013, vaccination was implemented in a sheep flock with 650 ewes associated with two outbreaks of Q fever in humans in 2008 and 2012. Only gimmers (yearlings) received two doses of a commercial C.burnetii phase I whole cell vaccine three weeks apart (primary vaccination) without any revaccination. Vaginal and nasal swabs collected shortly after lambing were tested by qPCR. Additionally, a group of non-vaccinated sentinels was serologically monitored for phase I (PhI), II (PhII) antibodies and for Interferon γ (IFN-γ) after stimulation of whole blood cells with PhII-antigen with and without an IL-10-neutralizing monoclonal antibody. In 2021, 679 sera collected in 2014-2021 were retested retrospectively with three commercial ELISA kits and one batch of an in-house PhI/PhII-ELISA. A low-level shedding of C.burnetii (<10
MeSH term(s)	Animals ; Coxiella burnetii ; Female ; Humans ; Q Fever/epidemiology ; Q Fever/prevention & control ; Q Fever/veterinary ; Retrospective Studies ; Sheep ; Sheep Diseases/epidemiology ; Sheep Diseases/microbiology ; Sheep Diseases/prevention & control ; Vaccination/veterinary
Language	English
Publishing date	2022-07-29
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	605674-x
ISSN	1873-2518 ; 0264-410X
ISSN (online)	1873-2518
ISSN	0264-410X
DOI	10.1016/j.vaccine.2022.07.029
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

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Article ; Online: Isolation and Cultivation of a New Isolate of BTV-25 and Presumptive Evidence for a Potential Persistent Infection in Healthy Goats.

Ries, Christina / Domes, Ursula / Janowetz, Britta / Böttcher, Jens / Burkhardt, Katinka / Miller, Thomas / Beer, Martin / Hoffmann, Bernd

Viruses

2020 Volume 12, Issue 9

Abstract: Recently, several so-called "atypical" Bluetongue virus (BTV) serotypes were discovered, including BTV-25 (Toggenburg virus), in Switzerland. Most "atypical" BTV were identified in small ruminants without clinical signs. In 2018, two goats from a holding ...

Abstract	Recently, several so-called "atypical" Bluetongue virus (BTV) serotypes were discovered, including BTV-25 (Toggenburg virus), in Switzerland. Most "atypical" BTV were identified in small ruminants without clinical signs. In 2018, two goats from a holding in Germany tested positive for BTV-25 genome by RT-qPCR prior to export. After experimental inoculation of the two goats with the BTV-25 positive field blood samples for generation of reference materials, viremia could be observed in one animal. For the first time, the BTV-25-related virus was isolated in cell culture from EDTA-blood and the full genome of isolate "BTV-25-GER2018" could be generated. BTV-25-GER2018 was only incompletely neutralized by ELISA-positive sera. We could monitor the BTV-25 occurrence in the respective affected goat flock of approximately 120 goats over several years. EDTA blood samples were screened with RT-qPCR using a newly developed BTV-25 specific assay. For serological surveillance, serum samples were screened using a commercial cELISA. BTV-25-GER2018 was detected over 4.5 years in the goat flock with intermittent PCR-positivity in some animals, and with or without concomitantly detected antibodies since 2015. We could demonstrate the viral persistence of BTV-25-GER2018 in goats for up to 4.5 years, and the first BTV-25 isolate is now available for further characterization.
MeSH term(s)	Animals ; Antibodies, Viral/blood ; Blood/virology ; Bluetongue/blood ; Bluetongue/virology ; Bluetongue virus/classification ; Bluetongue virus/genetics ; Bluetongue virus/growth & development ; Bluetongue virus/isolation & purification ; Genome, Viral ; Goat Diseases/blood ; Goat Diseases/virology ; Goats
Chemical Substances	Antibodies, Viral
Language	English
Publishing date	2020-09-04
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2516098-9
ISSN	1999-4915 ; 1999-4915
ISSN (online)	1999-4915
ISSN	1999-4915
DOI	10.3390/v12090983
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Isolation and Cultivation of a New Isolate of BTV-25 and Presumptive Evidence for a Potential Persistent Infection in Healthy Goats

Ries, Christina / Domes, Ursula / Janowetz, Britta / Böttcher, Jens / Burkhardt, Katinka / Miller, Thomas / Beer, Martin / Hoffmann, Bernd

2020

Abstract	Recently, several so-called “atypical” Bluetongue virus (BTV) serotypes were discovered, including BTV-25 (Toggenburg virus), in Switzerland. Most “atypical” BTV were identified in small ruminants without clinical signs. In 2018, two goats from a holding in Germany tested positive for BTV-25 genome by RT-qPCR prior to export. After experimental inoculation of the two goats with the BTV-25 positive field blood samples for generation of reference materials, viremia could be observed in one animal. For the first time, the BTV-25-related virus was isolated in cell culture from EDTA-blood and the full genome of isolate “BTV-25-GER2018” could be generated. BTV-25-GER2018 was only incompletely neutralized by ELISA-positive sera. We could monitor the BTV-25 occurrence in the respective affected goat flock of approximately 120 goats over several years. EDTA blood samples were screened with RT-qPCR using a newly developed BTV-25 specific assay. For serological surveillance, serum samples were screened using a commercial cELISA. BTV-25-GER2018 was detected over 4.5 years in the goat flock with intermittent PCR-positivity in some animals, and with or without concomitantly detected antibodies since 2015. We could demonstrate the viral persistence of BTV-25-GER2018 in goats for up to 4.5 years, and the first BTV-25 isolate is now available for further characterization.
Keywords	Text ; ddc:570 ; Bluetongue virus -- BTV -- atypical BTV -- serotype 25 -- persistent infection -- goats
Subject code	630
Language	English
Publishing date	2020-09-04
Publishing country	de
Document type	Article ; Online
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Article: Der PRRSV-Serumneutralisationstest detektiert Lücken in der Herdenimmunität.

Böttcher, Jens / Alex, Michaela / Janowetz, Britta / Müller, Silvia / Schuh, Christina / Niemeyer, Hermann

Berliner und Munchener tierarztliche Wochenschrift

2014 Volume 127, Issue 7-8, Page(s) 305–313

Abstract: Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) appears in two genotypes (EU and US), for both genotypes attenuated live-vaccines are available. A cross-sectional study in 38 Bavarian sow herds was performed to assess the level of ... ...

Title translation	The PRRSV-serumneutralization test detects gaps in herd immunity.
Abstract	Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) appears in two genotypes (EU and US), for both genotypes attenuated live-vaccines are available. A cross-sectional study in 38 Bavarian sow herds was performed to assess the level of neutralizing antibodies. Per herd 38 blood samples were collected (10 weaned piglets, 10 gilts and 6 sows of 1./2., 3J4. and 5/6. parity, respectively). Sera were tested by ELISA, serumneutralization test (SNT) against EU- and US-vaccine virus, and pooled sera were tested by real-time RT-PCR. Herds were classified by the last vaccination of sows as "Vacc EU" "Vacc US"and "nv (non-vaccinated) and by detection of PRRSV-US and vaccination of piglets were not included as variables. Sows of group (2) Vacc EU/EU- showed the highest EU-SNT-titers irrespective of parity. Groups (5) Vacc US/EU+ and (1) Vacc EU/EU+ followed in descending order. Significantly lower SNT-titers in (1) Vacc EU/EU+ were especially observed in sows of 1/2. Parity (Kruskal-Wallis, p < 0.05). Very low SNT-titers were observed in the three remaining groups (3) nv/EU+, (4) nv/EU- and (6) Vacc US/EU-. In US-vaccinated herds detection of PRRSV-EU coincided with strong ELISA-reactivity in all animal groups. In EU-vaccinated herds this was only observed for weaned piglets. Sows showed a strong ELISA-reactivity irrespective of detection of PRRSV-EU. The value of the ELISA is restricted to the certification of PRRSV-free herds. The EU-SNT reflects the level of herd immunity at least against vaccine virus; it indicates gaps in herd immunity.
MeSH term(s)	Animals ; Antibodies, Neutralizing/blood ; Antibodies, Viral/blood ; Cross-Sectional Studies ; Enzyme-Linked Immunosorbent Assay/veterinary ; European Union ; Female ; Genotype ; Germany ; Immunity, Herd ; Male ; Neutralization Tests/veterinary ; Porcine Reproductive and Respiratory Syndrome/immunology ; Porcine Reproductive and Respiratory Syndrome/prevention & control ; Porcine respiratory and reproductive syndrome virus/classification ; Porcine respiratory and reproductive syndrome virus/genetics ; Porcine respiratory and reproductive syndrome virus/immunology ; Swine ; Vaccines, Attenuated/immunology ; Viral Vaccines/immunology
Chemical Substances	Antibodies, Neutralizing ; Antibodies, Viral ; Vaccines, Attenuated ; Viral Vaccines
Language	German
Publishing date	2014-07
Publishing country	Germany
Document type	English Abstract ; Journal Article
ZDB-ID	5674-1
ISSN	0005-9366
ISSN	0005-9366
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: The impact of Q fever-phase-specific milk serology for the diagnosis of puerperal and chronic milk shedding of C. burnetii in dairy cows.

Böttcher, Jens / Frangoulidis, Dimitrios / Schumacher, Magdalena / Janowetz, Britta / Gangl, Armin / Alex, Michaela

Berliner und Munchener tierarztliche Wochenschrift

2013 Volume 126, Issue 9-10, Page(s) 427–435

Abstract: C. burnetii infection might be associated with puerperal shedding; additionally, the chronic shedding of this pathogen in milk has been observed in individual animals. A longitudinal survey was performed in an endemically infected dairy cow herd with 100 ...

Abstract	C. burnetii infection might be associated with puerperal shedding; additionally, the chronic shedding of this pathogen in milk has been observed in individual animals. A longitudinal survey was performed in an endemically infected dairy cow herd with 100 cows in order to compare phase-specific milk-serology with pathogen shedding. From March 2010 through December 2011, 870 individual milk samples from 212 cows were analysed using both quantitative (q) PCR and phase-specific antibody-ELISA. The mean milk-shedding/cow was calculated for 137 cows with > or = 3 milk samples per cow. In addition, 110 puerperal swabs were collected after August 2010. The cows yielding three successive qPCR-positive milk samples or > 3 qPCR-positive milk samples, irrespective of the sequence of positive/negative results, were classified as chronic shedders (CS). Milk shedding was observed during the entire study, but a major period of puerperal shedding occurred from February through October 2011; 35/52 swabs tested positive, whereas only 3/58 swabs collected outside this period were positive. The PhI/PhII(+)-pattern in primiparous cows (< 36 months old) was consistent with puerperal shedding in the herd, but not at the individual level. This pattern was observed in older cows, irrespective of the period of puerperal shedding. Four primiparous CS-cows showed low-level mean shedding < 100 C.b./ml milk, and the PhI-titre increased from negative or weakly positive to more than 500 at the end of the first lactation. Puerperal shedding during the second parturition was observed in three of these cows. Six multiparous CS-cows with mean shedding exceeding 100 C.b./ml milk were characterised with stable PhI-titres of > or = 500. The three available puerperal swabs tested negative. Only one multiparous CS-cow showed low-level shedding and a PhI-titre below 500 for the entire study. In conclusion, the PhI-/PhII(+)-pattern in primiparous cows indicated puerperal shedding at the herd level, and a PhI-titre > or = 500 is a suitable screening method for the detection of chronic shedding in milk.
MeSH term(s)	Animals ; Bacterial Shedding ; Cattle ; Cattle Diseases/diagnosis ; Cattle Diseases/microbiology ; Chronic Disease ; Coxiella burnetii/genetics ; Coxiella burnetii/immunology ; Coxiella burnetii/isolation & purification ; Enzyme-Linked Immunosorbent Assay/veterinary ; Female ; Longitudinal Studies ; Milk/microbiology ; Puerperal Infection/diagnosis ; Puerperal Infection/microbiology ; Puerperal Infection/veterinary ; Q Fever/diagnosis ; Q Fever/microbiology ; Q Fever/veterinary ; Real-Time Polymerase Chain Reaction/veterinary
Language	English
Publishing date	2013-09
Publishing country	Germany
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	5674-1
ISSN	0005-9366
ISSN	0005-9366
Database	MEDical Literature Analysis and Retrieval System OnLINE

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