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Book ; Online: Hurdles for Phage Therapy (PT) to Become a Reality

Brüssow, Harald

2019

Abstract: Alternative treatment modes for antibiotic-resistant bacterial pathogens have become a public health priority. Bacteriophages are bacterial viruses that infect and lyse bacterial cells. Since bacteriophages are frequently bacterial host species-specific ... ...

Abstract	Alternative treatment modes for antibiotic-resistant bacterial pathogens have become a public health priority. Bacteriophages are bacterial viruses that infect and lyse bacterial cells. Since bacteriophages are frequently bacterial host species-specific and can often also infect antibiotic-resistant bacterial cells, they could represent ideal antimicrobials for fighting the antibiotic resistance crisis. The medical use of bacteriophages has become known as phage therapy. It is widely used in Russia, where phage cocktails are sold in pharmacies as an over-the-counter drug. However, no phage product has been registered for medical purposes outside of the former Soviet Union. The current Special Issue of Viruses contains a collection of papers from opinion leaders in the field who explore hurdles to the introduction of phage therapy in western countries. The articles cover diverse topics ranging from patent to regulatory issues, the targeting of suitable bacterial infections, and the selection and characterization of safe and efficient phage cocktails. Phage resistance is discussed, and gaps in our knowledge of phage-bacterium interactions in the mammalian body are revealed, while other articles explore the use of phages in food production and processing
Keywords	Science (General) ; Biology (General) ; Microbiology
Size	1 electronic resource (484 pages)
Publisher	MDPI - Multidisciplinary Digital Publishing Institute
Document type	Book ; Online
Note	eng ; Open Access
HBZ-ID	HT020323941
ISBN	9783039213917 ; 9783039213924 ; 3039213911 ; 303921392X
DOI	10.3390/books978-3-03921-392-4
Database	ZB MED Catalogue: Medicine, Health, Nutrition, Environment, Agriculture

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Article ; Online: Pandemic preparedness: On the efficacy of non-pharmaceutical interventions in COVID-19 and about approaches to predict future pandemic viruses.

Brüssow, Harald

Microbial biotechnology

2024 Volume 17, Issue 3, Page(s) e14431

Abstract: With three major viral pandemics over the last 100 years, namely the Spanish flu, AIDS and COVID-19 each claiming many millions of lives, pandemic preparedness has become an important issue for public health. The economic, social and political ... ...

Abstract	With three major viral pandemics over the last 100 years, namely the Spanish flu, AIDS and COVID-19 each claiming many millions of lives, pandemic preparedness has become an important issue for public health. The economic, social and political consequences of the upheaval caused by such pandemics also represent a major challenge for governments with respect to sustainable development goals. The field of pandemic preparedness is vast and the current article can only address selected aspects. The article looks first backwards and addresses the question of the efficacy of non-pharmaceutical interventions (NPI) on the trajectory of the COVID-19 pandemic. The article looks then forward by asking to what extent viral candidates for future pandemics can be predicted by virome analyses from metagenome and transcriptome sequencing, by focusing on the virome from specific animal species and using ecological and epidemiological data about spillover viral infections in veterinary and human medicine. As a comprehensive overview on pandemic preparedness is beyond the capacity of a single reviewer, only selected topics will be discussed using recent key scientific publications. Since COVID-19 has not run its course, a computational program able to predict the future evolution of SARS-CoV-2 is mentioned that could assist proactive mRNA vaccine developments against possible future variants of concern. Ending the COVID-19 epidemic necessitates mucosal vaccines that can suppress the transmission of SARS-CoV-2 and therefore this article closes by discussing a promising and versatile protein nanoparticle experimental vaccine approach for inhalation that does not depend on needles nor a cold chain for distribution.
MeSH term(s)	Animals ; Humans ; COVID-19/epidemiology ; COVID-19/prevention & control ; Pandemic Preparedness ; Pandemics/prevention & control ; SARS-CoV-2/genetics
Language	English
Publishing date	2024-03-11
Publishing country	United States
Document type	Journal Article
ZDB-ID	2406063-X
ISSN	1751-7915 ; 1751-7915
ISSN (online)	1751-7915
ISSN	1751-7915
DOI	10.1111/1751-7915.14431
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Avian influenza virus cross-infections as test case for pandemic preparedness: From epidemiological hazard models to sequence-based early viral warning systems.

Brüssow, Harald

Microbial biotechnology

2024 Volume 17, Issue 1, Page(s) e14389

Abstract: Pandemic preparedness starts with an early warning system of viruses with a pandemic potential. Based on information collected in a multitude of surveys, hazard models were developed identifying influenza viruses presenting a pandemic threat. Scores are ... ...

Abstract	Pandemic preparedness starts with an early warning system of viruses with a pandemic potential. Based on information collected in a multitude of surveys, hazard models were developed identifying influenza viruses presenting a pandemic threat. Scores are attributed for 10 viral traits by expert panels which identified avian influenza viruses (AIV) belonging to subtypes H7N9 and H5N1 as representing the greatest pandemic risk. In 2013, more than 100 human cases infected with AIV H7N9 were observed in China. Case fatality rate (CFR) was high (27%), but the human-to-human transmission rate was low and by serological evidence H7N9 did not spread widely. Nevertheless, until 2019 more than 1500 H7N9 patients were identified characterized by a high CFR of 39%. Serology demonstrated that mild infections with H7N9 were widespread. In 2003, more than 400 people experienced AIV H7N7 cross-infection causing mainly conjunctivitis during a large poultry epidemic in The Netherlands. Between 1996 and 2019, a total of 881 human infections with avian H5N1 viruses were documented showing a CFR of 52%. Outbreaks were centred on South East Asia and showed close associations with epizootics in poultry. Mutations predisposing to human cross-infections were identified in the haemagglutinin (HA) and the RNA polymerase subunit PB2 of human H7N9 isolates. Human H5N1 isolates showed mutations in the receptor binding domain of HA and transmission in mammals could be obtained by as few as four additional aa changes introduced experimentally. Researchers have defined viral point mutations in HA, PB2 and the nucleoprotein NP that allowed AIV to cross the species barrier to mammals with respect to receptor recognition, RNA replication and escape from innate immunity respectively. Based on this insight a sequence-based early warning system for AIV preadapted to human transmission could be envisioned. Mink farms and live poultry markets are prime targets for such sequencing efforts.
MeSH term(s)	Animals ; Humans ; Influenza in Birds/epidemiology ; Influenza, Human/epidemiology ; Influenza A Virus, H5N1 Subtype/genetics ; Influenza A Virus, H7N9 Subtype/genetics ; Pandemic Preparedness ; Influenza A Virus, H7N7 Subtype ; Proportional Hazards Models ; Mammals
Language	English
Publishing date	2024-01-16
Publishing country	United States
Document type	Journal Article
ZDB-ID	2406063-X
ISSN	1751-7915 ; 1751-7915
ISSN (online)	1751-7915
ISSN	1751-7915
DOI	10.1111/1751-7915.14389
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: The human microbiome project at ten years - some critical comments and reflections on "our third genome", the human virome.

Brüssow, Harald

Microbiome research reports

2023 Volume 2, Issue 1, Page(s) 7

Abstract: The Human Microbiome Project (HMP) has raised great expectations claiming the far-reaching influence of the microbiome on human health and disease ranging from obesity and malnutrition to effects going well beyond the gut. So far, with the notable ... ...

Abstract	The Human Microbiome Project (HMP) has raised great expectations claiming the far-reaching influence of the microbiome on human health and disease ranging from obesity and malnutrition to effects going well beyond the gut. So far, with the notable exception of fecal microbiota transplantation in
Language	English
Publishing date	2023-03-29
Publishing country	United States
Document type	Journal Article
ISSN	2771-5965
ISSN (online)	2771-5965
DOI	10.20517/mrr.2022.20
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Viral infections at the animal-human interface-Learning lessons from the SARS-CoV-2 pandemic.

Brüssow, Harald

Microbial biotechnology

2023 Volume 16, Issue 7, Page(s) 1397–1411

Abstract: This Lilliput explores the current epidemiological and virological arguments for a zoonotic origin of the COVID-19 pandemic. While the role of bats, pangolins and racoon dogs as viral reservoirs has not yet been proven, a spill-over of a coronavirus ... ...

Abstract	This Lilliput explores the current epidemiological and virological arguments for a zoonotic origin of the COVID-19 pandemic. While the role of bats, pangolins and racoon dogs as viral reservoirs has not yet been proven, a spill-over of a coronavirus infection from animals into humans at the Huanan food market in Wuhan has a much greater plausibility than alternative hypotheses such as a laboratory virus escape, deliberate genetic engineering or introduction by cold chain food products. This Lilliput highlights the dynamic nature of the animal-human interface for viral cross-infections from humans into feral white tail deer or farmed minks (reverse zoonosis). Surveillance of viral infections at the animal-human interface is an urgent task since live animal markets are not the only risks for future viral spill-overs. Climate change will induce animal migration which leads to viral exchanges between animal species that have not met in the past. Environmental change and deforestation will also increase contact between animals and humans. Developing an early warning system for emerging viral infections becomes thus a societal necessity not only for human but also for animal and environmental health (One Health concept). Microbiologists have developed tools ranging from virome analysis in key suspects such as viral reservoirs (bats, wild game animals, bushmeat) and in humans exposed to wild animals, to wastewater analysis to detect known and unknown viruses circulating in the human population and sentinel studies in animal-exposed patients with fever. Criteria need to be developed to assess the virulence and transmissibility of zoonotic viruses. An early virus warning system is costly and will need political lobbying. The accelerating number of viral infections with pandemic potential over the last decades should provide the public pressure to extend pandemic preparedness for the inclusion of early viral alert systems.
MeSH term(s)	Dogs ; Humans ; Animals ; SARS-CoV-2 ; COVID-19/epidemiology ; Pandemics ; Chiroptera ; Deer ; Virus Diseases/epidemiology ; Virus Diseases/veterinary ; Animals, Wild ; Viruses
Language	English
Publishing date	2023-05-08
Publishing country	United States
Document type	Journal Article
ZDB-ID	2406063-X
ISSN	1751-7915 ; 1751-7915
ISSN (online)	1751-7915
ISSN	1751-7915
DOI	10.1111/1751-7915.14269
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Pandemic potential of poxviruses: From an ancient killer causing smallpox to the surge of monkeypox.

Brüssow, Harald

Microbial biotechnology

2023 Volume 16, Issue 9, Page(s) 1723–1735

Abstract: Smallpox caused by the variola virus (VARV) was one of the greatest infectious killers of mankind. Historical records trace back smallpox for at least a millennium while phylogenetic analysis dated the ancestor of VARV circulating in the 20th century ... ...

Abstract	Smallpox caused by the variola virus (VARV) was one of the greatest infectious killers of mankind. Historical records trace back smallpox for at least a millennium while phylogenetic analysis dated the ancestor of VARV circulating in the 20th century into the 19th century. The discrepancy was solved by the detection of distinct VARV sequences first in 17th-century mummies and then in human skeletons dated to the 7th century. The historical records noted marked variability in VARV virulence which scientists tentatively associated with gene losses occurring when broad-host poxviruses narrow their host range to a single host. VARV split from camel and gerbil poxviruses and had no animal reservoir, a prerequisite for its eradication led by WHO. The search for residual pockets of VARV led to the discovery of the monkeypox virus (MPXV); followed by the detection of endemic smallpox-like monkeypox (mpox) disease in Africa. Mpox is caused by less virulent clade 2 MPXV in West Africa and more virulent clade 1 MPXV in Central Africa. Exported clade 2 mpox cases associated with the pet animal trade were observed in 2003 in the USA. In 2022 a world-wide mpox epidemic infecting more than 80,000 people was noted, peaking in August 2022 although waning rapidly. The cases displayed particular epidemiological characteristics affecting nearly exclusively young men having sex with men (MSM). In contrast, mpox in Africa mostly affects children by non-sexual transmission routes possibly from uncharacterized animal reservoirs. While African children show a classical smallpox picture, MSM mpox cases show few mostly anogenital lesions, low-hospitalization rates and 140 fatal cases worldwide. MPXV strains from North America and Europe are closely related, derived from clade 2 African MPXV. Distinct transmission mechanisms are more likely causes for the epidemiological and clinical differences between endemic African cases and the 2022 epidemic cases than viral traits.
MeSH term(s)	Male ; Child ; Humans ; Variola virus/genetics ; Smallpox/epidemiology ; Smallpox/history ; Mpox (monkeypox)/epidemiology ; Poxviridae/genetics ; Pandemics ; Phylogeny ; Homosexuality, Male ; Sexual and Gender Minorities ; Monkeypox virus/genetics
Language	English
Publishing date	2023-06-19
Publishing country	United States
Document type	Journal Article
ZDB-ID	2406063-X
ISSN	1751-7915 ; 1751-7915
ISSN (online)	1751-7915
ISSN	1751-7915
DOI	10.1111/1751-7915.14294
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Non-A to E hepatitis in children: Detecting a novel viral epidemic during the COVID-19 pandemic.

Brüssow, Harald

Microbial biotechnology

2023 Volume 16, Issue 10, Page(s) 1879–1887

Abstract: During the COVID-19 pandemic, two further novel viral epidemics were described in 2022, monkeypox virus infections in men having sex with men and non-A to E hepatitis in children. The latter occurred in the first half of 2022 with about 1000 cases ... ...

Abstract	During the COVID-19 pandemic, two further novel viral epidemics were described in 2022, monkeypox virus infections in men having sex with men and non-A to E hepatitis in children. The latter occurred in the first half of 2022 with about 1000 cases worldwide, necessitating liver transplantation in 5% and causing death in 2% of patients. It took some effort to clarify the cause of the novel hepatitis epidemic. Researchers were confronted with a polymicrobial viral infection consisting of an adenovirus-associated virus type 2 (AAV2) infection, co-occurring with either human adenovirus type 41 (HAdV41) or herpesvirus infections; most prominently human herpesvirus type 6 (HHV-6). AAV-2, a small Dependovirus of the Parvovirus family, needs these helper viruses for its replication. AAV2 is used as a vector for liver-targeting gene therapy but was not previously known to cause acute hepatitis. HAdV41 and HHV-6 are mostly known to cause diarrhoea and febrile illnesses associated with skin rashes in children, respectively. Except for a few case reports of HHV-6 hepatitis, HAdV and HHV-6 are mostly known as major pathogens in immunosuppressed transplantation patients. A potential role of SARS-CoV-2 has also been discussed but the most popular hypothesis involves an indirect role of the COVID-19 pandemic for this novel disease. Exposure to HHV-6 infections occurs nearly quantitatively during the first year of life. Social distancing measures, followed by the lifting of these measures in 2022 might have caused a delayed exposure to multiple, normally benign childhood viral infections eliciting a dysregulated immune response with pathological effects for liver cells. In the fall of 2022, when these conditions were not longer met, case numbers dwindled. The hypothesis of an unequilibrated immune response instead of intrinsic cytopathic activity of the implicated viruses is further supported by the enrichment of a particular HLA allele in cases over controls.
MeSH term(s)	Male ; Humans ; Child ; Pandemics ; COVID-19/epidemiology ; SARS-CoV-2 ; Virus Diseases ; Roseolovirus Infections/complications
Language	English
Publishing date	2023-08-21
Publishing country	United States
Document type	Editorial
ZDB-ID	2406063-X
ISSN	1751-7915 ; 1751-7915
ISSN (online)	1751-7915
ISSN	1751-7915
DOI	10.1111/1751-7915.14329
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: What is truth - in science and beyond.

Brüssow, Harald

Environmental microbiology

2022 Volume 24, Issue 7, Page(s) 2895–2906

Abstract: Truth is threatened in our societies and one might wish that scientists should stand up for truth, but in order to do so, one needs to know what is truth and how it can be recognized. The oldest and most widely accepted concept of truth is the ... ...

Abstract	Truth is threatened in our societies and one might wish that scientists should stand up for truth, but in order to do so, one needs to know what is truth and how it can be recognized. The oldest and most widely accepted concept of truth is the Correspondence Theory requesting a fit of propositions and reality. In the Coherence Theory truth is a consistent property of a whole system of propositions. In the Pragmatic Theory truth works in practical terms. Scientists have defined criteria to verify true statements by experiments and by the simplicity of theories. Aristotle proposed parsimony claiming the superiority of theories which derive from fewer hypotheses. David Hume suggested probability arguments to assess the force of evidence. Nicolai Hartmann elaborated a model based on the congruence of a priori logical arguments with a posteriori empirical observations. Karl Popper introduced the falsification of testable theories as a way to better theories. The analysis shows that scientific and medical research uses classical philosophical criteria of truth in their daily work. Humanities use different, hermeneutic criteria of truth. Finally, societies need for their coherence a dialectic approach to truth based on honest discussion of opposing views.
MeSH term(s)	Philosophy
Language	English
Publishing date	2022-06-05
Publishing country	England
Document type	Journal Article
ZDB-ID	2020213-1
ISSN	1462-2920 ; 1462-2912
ISSN (online)	1462-2920
ISSN	1462-2912
DOI	10.1111/1462-2920.16080
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: On opinion, freedom of speech and its responsibilities.

Brüssow, Harald

Microbial biotechnology

2022 Volume 15, Issue 10, Page(s) 2507–2517

Abstract: Plato and Aristotle place opinion intermediate between knowledge and ignorance with all opinions under the suspicion of error. Kant summarized that opinion is a consciously insufficient judgement, subjectively and objectively. Belief is subjectively ... ...

Abstract	Plato and Aristotle place opinion intermediate between knowledge and ignorance with all opinions under the suspicion of error. Kant summarized that opinion is a consciously insufficient judgement, subjectively and objectively. Belief is subjectively sufficient, but is recognized as being objectively insufficient. Only knowledge is subjectively and objectively sufficient. Despite this philosophically doubtful value of opinions, thinkers such as Milton, Locke, Montesquieu and Mill maintain that the freedom of opinion and speech are the basis of open societies but find limits when it represents a definite risk of damage, either to an individual or to the public. Also the UN Covenant on Civil and Political Rights proclaims the right to hold opinions without interference provided that it respects the rights or reputations of others and does not interfere with the protection of public health. Hate speech and propaganda for war are expressively prohibited. Postwar US politicians formulated the position that every man has a right to his own opinion, but no man has a right to be wrong in his facts. The impact of this discussion on opinions about control measures of the COVID-19 pandemic is explored in this editorial.
MeSH term(s)	COVID-19 ; Freedom ; Humans ; Pandemics ; Speech
Language	English
Publishing date	2022-07-13
Publishing country	United States
Document type	Journal Article
ZDB-ID	2406063-X
ISSN	1751-7915 ; 1751-7915
ISSN (online)	1751-7915
ISSN	1751-7915
DOI	10.1111/1751-7915.14119
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Article ; Online: On the role of hypotheses in science.

Brüssow, Harald

Microbial biotechnology

2022 Volume 15, Issue 11, Page(s) 2687–2698

Abstract: Scientific research progresses by the dialectic dialogue between hypothesis building and the experimental testing of these hypotheses. Microbiologists as biologists in general can rely on an increasing set of sophisticated experimental methods for ... ...

Abstract	Scientific research progresses by the dialectic dialogue between hypothesis building and the experimental testing of these hypotheses. Microbiologists as biologists in general can rely on an increasing set of sophisticated experimental methods for hypothesis testing such that many scientists maintain that progress in biology essentially comes with new experimental tools. While this is certainly true, the importance of hypothesis building in science should not be neglected. Some scientists rely on intuition for hypothesis building. However, there is also a large body of philosophical thinking on hypothesis building whose knowledge may be of use to young scientists. The present essay presents a primer into philosophical thoughts on hypothesis building and illustrates it with two hypotheses that played a major role in the history of science (the parallel axiom and the fifth element hypothesis). It continues with philosophical concepts on hypotheses as a calculus that fits observations (Copernicus), the need for plausibility (Descartes and Gilbert) and for explicatory power imposing a strong selection on theories (Darwin, James and Dewey). Galilei introduced and James and Poincaré later justified the reductionist principle in hypothesis building. Waddington stressed the feed-forward aspect of fruitful hypothesis building, while Poincaré called for a dialogue between experiment and hypothesis and distinguished false, true, fruitful and dangerous hypotheses. Theoretical biology plays a much lesser role than theoretical physics because physical thinking strives for unification principle across the universe while biology is confronted with a breathtaking diversity of life forms and its historical development on a single planet. Knowledge of the philosophical foundations on hypothesis building in science might stimulate more hypothesis-driven experimentation that simple observation-oriented "fishing expeditions" in biological research.
Language	English
Publishing date	2022-09-13
Publishing country	United States
Document type	Journal Article
ZDB-ID	2406063-X
ISSN	1751-7915 ; 1751-7915
ISSN (online)	1751-7915
ISSN	1751-7915
DOI	10.1111/1751-7915.14141
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