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Deadly hospital-acquired infections (HAIs) might be ‘Disease X’

22 February 2024 | Story André Damons | Photo SUPPLIED

Prof Robert Bragg is a researcher in the Department of Microbiology and Biochemistry at the University of the Free State (UFS) and believes hospital-acquired infections (HAIs) might already be “Disease X”.

During the World Governments Summit, the World Health Organisation (WHO) warned world leaders about the likelihood of a Disease X outbreak, saying it is “a matter of when, not if” a new pathogen and pandemic will strike. If there is an outbreak of this disease tomorrow, the world still would not be ready.

During his speech earlier this month at the summit in Dubai, Tedros Adhanom Ghebreyesus, Director-General of the WHO, said COVID-19 was a Disease X – a new pathogen causing a new disease. He said: “There will be another Disease X, or a Disease Y or a Disease Z. And as things stand, the world remains unprepared for the next Disease X, and the next pandemic. If it struck tomorrow, we would face many of the same problems we faced with COVID-19.”

Though Disease X is a hypothetical placeholder representing yet-to-be-encountered pathogens, Prof Robert Bragg, researcher in the Department of Microbiology and Biochemistry at the University of the Free State (UFS), believes hospital-acquired infections (HAI) might already be “Disease X”. He says data shows that deaths from HAIs will become the leading cause of human deaths. This problem is rapidly growing as most of the pathogens which people contract while in hospital are now resistant to antibiotics, making them very difficult to treat.

Prof Bragg, whose main research is in disease-control, first in the agricultural industry, and now human health, also previously warned about a disease that would make COVID-19, which killed more than seven million people to date globally, look like a dress rehearsal. His PhD student, Samantha Mc Carlie, investigating how bacteria become resistant to disinfectant and sanitiser products. This is a serious problem for the future, as disinfection could be our last line of defence.

Heading for a crisis in health care

“The world is rapidly heading for a crisis in health care regarding hospital-acquired infections. It is common knowledge that we are quickly running out of antibiotics (and antifungals) to treat bacterial and yeast infections. Without antibiotics and antifungals, the outcome of many of these bacterial and yeast hospital-acquired infections will be very severe. They will, unfortunately, in many cases, result in the death of the patient,” says Prof Bragg.

According to him, the WHO suggests that 30% of patients in ICUs in developed countries and 70% in underdeveloped countries will contract a HAI. Of these, the mortality rate can be as high as 70%.

“Most of these infections are caused by multiple drug resistance strains of bacteria such as Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter species. Additional bacteria and yeast, which can also cause HAIs, such as Serratia species, are also becoming a concern due to their intrinsic higher levels of disinfectant resistance.”

Prof Bragg explains that in 2014, a high-profile review was first published, commissioned by the UK Prime Minister, entitled, “Antimicrobial Resistance: Tackling a crisis for the Health and Wealth of Nations” (the AMR Review). This review estimated that antimicrobial resistance (AMR) could cause 10 million deaths annually by 2050 (The Review on Antimicrobial Resistance 2016). This is the same number of deaths caused by cancer today, making AMR the leading cause of human mortality by 2050. When it was finalised, this report was highly criticised as an over-dramatisation, as when this prediction was made, the number of mortalities related to HAIs was around 700 000 – a very long way off 10 000 000. However, according to recent estimates, five years later, in 2019, 1.27 million deaths were directly attributed to drug-resistant infections globally, and this had reached 4.95 million deaths associated with bacterial AMR (including those directly attributable to AMR) by 2022 (Murray et al. 2022).

The overuse of disinfectants during the COVID-19 pandemic, according to Prof Bragg and Mc Calie, has contributed to the crisis by fostering resistant strains and contaminating environments. Based on the current trajectory of mortalities, the 10 million mark will be reached way before 2050.

Need for a paradigm shift

The researchers say an urgent need to change the paradigm in medicine from “treatment” to “prevention” is necessary and that the old saying ‘prevention is better than cure’ has never been truer.

According to Bragg: “The golden era of antibiotics is rapidly coming to an end. It is highly unlikely that we will discover new antibiotics, and even if we do, the likelihood that the bacteria will already have or will be able to develop resistance in a very short time is highly likely.

“We need to think of what happed with quinolones, where we thought we had won the war with a groundbreaking new antimicrobial agent. The bacteria did not have millions of years of evolution to develop resistance to quinolone, yet in only three years, the first resistant bacteria were isolated. There is currently great excitement around AI-derived new antibiotics. However, the end result is likely to be the same. We need an alternative to treatment – in other words, a paradigm shift.”

Improved biosecurity

Prof Bragg says highly improved biosecurity is the only viable option for disease control in a post-antibiotic era. By using good biosecurity in poultry production, he says the mortality rates were reduced by 50%.

Research has shown a direct link between the environmental microbial load in a hospital and HAIs; with a lower microbial load linked to lower incidence of HAIs including C. difficile infections (Boyce et al. 2008; Suleyman et al. 2018; Umemura et al., 2022). Therefore, the new paradigm is to reduce microbial contamination in the hospital environment to prevent HAIs. If there are fewer dangerous microorganisms in an environment, patient and staff exposure to these microorganisms will decrease, reducing the level of HAIs for staff and patients. However, to reduce the microbial loads in healthcare settings, effective cleaning and disinfection products need to be used.

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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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