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14 April 2023 | Story Prof Robert Bragg, Wanja Swart and Samantha Mc Carlie | Photo Supplied
Prof Robert Bragg, Wanja Swart, and Samantha Mc Carlie
Prof Robert Bragg, Wanja Swart, and Samantha Mc Carlie are from the Infection Control Group within the Veterinary Biotechnology Research Group, Department of Microbiology and Biochemistry, University of the Free State.

Opinion article by Prof Robert Bragg, Wanja Swart, and Samantha Mc Carlie, Infection Control Group within the Veterinary Biotechnology Research Group, Department of Microbiology and Biochemistry, University of the Free State.

The storm is coming, and it has, in fact, already had significant effects in health care and agriculture. This is the storm of resistance to disinfectants. 

In the age where antibiotics are ever decreasing in efficacy and the search for novel antimicrobials is not progressing very well, our last line of defence against bacterial diseases is biosecurity. Biosecurity is the concept of preventing the infection before the individual becomes infected. The individual can be human, animal or plant. The main weapons in the arsenal for good biosecurity are disinfectants and sanitisers, of which there are many. In fact, way too many! Many of these disinfectants are not used correctly, and in many cases, there is no effort to monitor the efficacy of the disinfectants used in a particular situation. Many of these are not registered for use and have never been tested in a clinical setting. This is a big part of the problem.

Antibiotic resistance is a well-known global crisis currently challenging the healthcare community. However, the COVID-19 pandemic has highlighted our reliance on disinfectants and sanitisers as infection control measures. In 2020 alone, it was estimated that 700 000 tons of quaternary ammonium compound (QAC)-based disinfectants were released into the environment. The presence of these disinfectants environmentally leads to selection for resistant microorganisms and can lead to the development of resistant populations in our water systems, on farms, and around hospitals. This has prompted the Infection Control research group at the UFS to explore new research regarding microbial resistance to disinfectant and sanitiser compounds, as well as whether resistance to disinfectants and antibiotics is linked. 

The coming storm in health care

Nosocomial infections, otherwise known as hospital-acquired infections (HAIs), affect 30% of ICU patients in high-income countries and up to 70% in low-income countries, with more than 52% of these infections being fatal. According to the World Health Organisation (WHO), HAIs are also responsible for up to 56% of all deaths in neonates. 

In 2014, an article was published with a powerful title: The future if we do not act now, where the author stated that if we do not address antimicrobial resistance (AMR), it will be responsible for the death of 10 million individuals by the year 2050, which would make it a bigger killer than cancer today. This information was widely regarded as an over-dramatisation as, at the time, AMR was estimated to have claimed the lives of 700 000 individuals annually. However, the WHO estimated that AMR was directly responsible for 1,27 million deaths in 2019 and 4,95 million deaths in 2022. It is now becoming abundantly clear that this article was not an over-dramatisation, and the number of 10 million mortalities will be reached long before 2050. We are already halfway there in 2022.

With health care being the environment where most cases of AMR and HAIs occur in conjunction, it is concerning that research is underway that shows exponential increases in resistance when bacteria are exposed to sub-minimum levels of disinfectants regularly used within the health-care setting.

The coming storm in agriculture

The need to reduce the use of antibiotics in agriculture has been in place for several years now. The concept of biosecurity is well established in the agricultural sector, but disinfectants are still being misused. It is difficult to produce meat products without the use of antibiotics; this will result in an increase in the cost of meat products, which will put it beyond the reach of many people. Good biosecurity is essential in the animal production area, and this research group has been working in the area for many years. The experience gained in this field is now being applied to the healthcare setting. If we can reduce mortalities in a poultry pen by 56% through good biosecurity prevention practices, it should certainly be possible to achieve similar or much better results in the health-care sector. 

Research on the mechanisms of disinfectant resistance

Current projects in Prof Robert Bragg’s laboratory include a PhD by Samantha Mc Carlie, investigating how bacteria become resistant to disinfectant and sanitiser products. A highly resistant ‘superbug’ bacterium related to Serratia marcescens has been discovered, and Mc Carlie is working with this isolate to determine the reason for the high level of resistance to disinfectant and sanitiser products. This work is being done on a genetic level to reveal which resistance genes and metabolic systems are responsible for high levels of antimicrobial resistance. Master of Science (MSc) projects by Boudine van der Walt and Wanja Swart are investigating how disinfectant resistance is transferred between bacterial species, and whether disinfectant resistance and antibiotic resistance are linked. Wanja Swart’s MSc project focuses on investigating the simultaneous development of antibiotic and disinfectant resistance within one bacterium. Resistance occurs despite the absence of one of these products in a familiar nosocomial pathogen, Serratia marcescens. Gene-based analysis will shed light on how these mechanisms present on a genetic level. In addition, resistance to disinfectants and antibiotics may be inducted to higher levels, which could provide new insights to just how dangerous incorrectly used disinfectants can be.

Gunther Staats has just completed yet another MSc project, focusing on efflux pumps that pump out antimicrobial agents from the inside of bacterial cells. 


Evaluation of the efficacy of disinfectants 

Registration of disinfectants, where applicable, has specific guidelines according to which bacterial pathogens need to be tested against these products. The required cultures are generally environmental reference ATCC (American type culture collection) strains, which ensure consistency and fair treatment when doing product registration. 

However, the situation in the field, farm, or hospital ward may be very different. The pathogens that are found in these settings may be totally different from the ATCC strains, as they are regularly challenged with disinfectants and antibiotics. 

Work performed by Wanja Swart showed that in just 10 consecutive days of exposure to disinfectants, resistance to commonly used disinfectants can increase 32-fold. So why is this important? Firstly, accurate dilution of disinfectants appears to be a challenge for many, so the likelihood of the products being used correctly is relatively small. Also, some of the products have substantial residual activity on surfaces. This will result in the exposure of bacteria to sub-lethal levels for extended periods of time as well as a build-up of disinfectant – which will in turn result in a further increase in resistance. 

Research outputs so far for 2023 include two publications by Samantha Mc Carlie on bacterial resistance to disinfectants in the accredited peer-reviewed journal, Microorganisms, titled ‘Genomic Islands Identified in Highly Resistant Serratia sp. HRI: A Pathway to Discover New Disinfectant Resistance Elements’ and ‘The Hermetic Effect Observed for Benzalkonium Chloride and Didecyldimethylammonium Chloride in Serratia sp. HRI’. In addition, three book chapters have been published in the book Antimicrobial Resistance and One Health in Africa by Springer Publishers, titled ‘Biosecurity and Disinfectant resistance in a Post-antibiotic era’, ‘The Linkage between Antibiotic and Disinfectant Resistance’, and ‘The Current State of Antimicrobial resistance in Bovine Mastitis in Various African Countries’.

News Archive

Inaugural lecture: Prof Robert Bragg, Dept. of Microbial, Biochemical and Food Biotechnology
2006-05-17



Attending the inaugural lecture were in front from the left Prof Robert Bragg (lecturer at the Department of Microbial, Biochemical and Food Biotechnology) and Frederick Fourie (Rector and Vice-Chancellor).  At the back from the left were Prof James du Preez (Departmental Chairperson:  Department of Microbial, Biochemical and Food Biotechnology) and Prof Herman van Schalkwyk (Dean: Faculty of Natural and Agricultural Sciences). Photo: Stephen Collett
 

A summary of an inaugural lecture delivered by Prof Robert Bragg at the University of the Free State:

CONTROL OF INFECTIOUS AVIAN DISEASES – LESSONS FOR MAN?

Prof Robert R Bragg
Department of Microbial, Biochemical and Food Biotechnology
University of the Free State

“Many of the lessons learnt in disease control in poultry will have application on human medicine,” said Prof Robert Bragg, lecturer at the University of the Free State’s (UFS) Department of Microbial, Biochemical and Food Biotechnology during his inaugural lecture.

Prof Bragg said the development of vaccines remains the main stay of disease control in humans as well as in avian species.  Disease control can not rely on vaccination alone and other disease-control options must be examined.  

“With the increasing problems of antibiotic resistance, the use of disinfection and bio security are becoming more important,” he said.

“Avian influenza (AI) is an example of a disease which can spread from birds to humans.  Hopefully this virus will not develop human to human transmission,” said Prof Bragg.

According to Prof Bragg, South Africa is not on the migration route of water birds, which are the main transmitters of AI.  “This makes South Africa one of the countries less likely to get the disease,” he said.

If the AI virus does develop human to human transmission, it could make the 1918 flu pandemic pale into insignificance.  During the 1918 flu pandemic, the virus had a mortality rate of only 3%, yet more than 50 million people died.

Although the AI virus has not developed human-to-human transmission, all human cases have been related to direct contact with infected birds. The mortality rate in humans who have contracted this virus is 67%.

“Apart from the obvious fears for the human population, this virus is a very serious poultry pathogen and can cause 100% mortality in poultry populations.  Poultry meat and egg production is the staple protein source in most countries around the world. The virus is currently devastating the poultry industry world-wide,” said Prof Bragg.

Prof Bragg’s research activities on avian diseases started off with the investigation of diseases in poultry.  “The average life cycle of a broiler chicken is 42 days.  After this short time, they are slaughtered.  As a result of the short generation time in poultry, one can observe changes in microbial populations as a result of the use of vaccines, antibiotics and disinfectants,” said Prof Bragg.   

“Much of my research effort has been directed towards the control of infectious coryza in layers, which is caused by the bacterium Avibacterium paragallinarum.  This disease is a type of sinusitis in the layer chickens and can cause a drop in egg product of up to 40%,” said Prof Bragg.

The vaccines used around the world in an attempt to control this disease are all inactivated vaccines. One of the most important points is the selection of the correct strains of the bacterium to use in the vaccine.

Prof Bragg established that in South Africa, there are four different serovars of the bacterium and one of these, the serovar C-3 strain, was believed to be unique to Southern Africa. He also recently discovered this serovar for the first time in Israel, thus indicating that this serovar might have a wider distribution than originally believed.

Vaccines used in this country did not contain this serovar.  Prof Bragg established that the long term use of vaccines not containing the local South African strain resulted in a shift in the population distribution of the pathogen.

Prof Bragg’s research activities also include disease control in parrots and pigeons.   “One of the main research projects in my group is on the disease in parrots caused by the circovirus Beak and Feather Disease virus. This virus causes serious problems in the parrot breeding industry in this country. This virus is also threatening the highly endangered and endemic Cape Parrot,” said Prof Bragg.

Prof Bragg’s research group is currently working on the development of a DNA vaccine which will assist in the control of the disease, not only in the parrot breeding industry, but also to help the highly endangered Cape Parrot in its battle for survival.

“Not all of our research efforts are directed towards infectious coryza or the Beak and Feather Disease virus.  One of my Masters students is currently investigating the cell receptors involved in the binding of Newcastle Disease virus to cancerous cells and normal cells of humans. This work will also eventually lead to a possible treatment of cancer in humans and will assist with the development of a recombinant vaccine for Newcastle disease virus,” said Prof Bragg.

We are also currently investigating an “unknown” virus which causes disease problems in poultry in the Western Cape,” said Prof Bragg.
 
“Although disinfection has been extensively used in the poultry industry, it has only been done at the pre-placement stage. In other words, disinfectants are used before the birds are placed into the house. Once the birds are placed, all use of disinfectants stops,” said Prof Bragg.

“Disinfection and bio security can be seen as the ‘Cinderella’ of disease control in poultry.  This is also true for human medicine. One just has to look at the high numbers of people who die from hospital-acquired infections to realise that disinfection is not a concept which is really clear in human health care,” said Prof Bragg.

Much research has been done in the control of diseases through vaccination and through the use of antibiotics. “These pillars of disease control are, however, starting to crumble and more effort is needed on disinfection and bio security,” said Prof Bragg.

Prof Bragg has been working in close co-operation with a chemical manufacturing company in Stellenbosch to develop a unique disinfectant which his highly effective yet not toxic to the birds.

As a result of this unique product, he has developed the continual disinfection program for use in poultry. In this program the disinfectant is used throughout the production cycle of the birds. It is also used to ensure that there is excellent pre-placement disinfection.

“The program is extensively used for the control of infectious diseases in the parrot-breeding industry in South Africa and the product has been registered in 15 countries around the world with registration in the USA in the final process,” said Prof Bragg.

“Although the problem of plasmid mediated resistance to disinfectants is starting to rear its ugly head, this has allowed for the opening of a new research field which my group will hopefully exploit in the near future,” he said.

 

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