“Antimicrobial resistance (AMR) is a major public-health problem worldwide. AMR is currently estimated to cause 700 000 deaths globally per year. But it’s estimated that by 2050 up to 10 million will die annually due to AMR,” said Iso Lomso fellow Jerrold Agbankpe of the Bacteriology Research Unit at the Institut Pasteur of Guinea. “Currently more people die of AMR in Africa and Asia, and going forward are likely to be most affected because of infrastructural problems and lack of regulation, along with misuse in humans and animals.”
“To address this situation and, in particular, to respond to the serious infectious diseases caused by multi-resistant bacteria, European and American researchers have turned to a therapeutic agent discovered around a 100 years ago called bacteriophages or phages. Phage therapy has proved its worth, and its development is currently booming. But where does Africa stand in the use of phage therapy as an alternative and/or complement in the fight against antimicrobial resistance? How are the continent’s scientists, policy makers and communities dealing with this therapeutic solution?”
Agbankpe explained that microbes or microorganisms are the smallest living things we know – they are found in the air, in soil and in our bodies. The most common are bacteria, parasites, viruses and fungi. They play an essential role in digestion, protection against infection and contribute to the ecosystem, but some are also harmful.
Antimicrobial drugs are used to prevent and treat microbial infections in humans, animals and plants and include antibiotics, antifungals, antiparasitics and antivirals.
“Roughly 30 years after the development of antibiotics, resistance was noticed. Such resistance occurs when pathogens develop the ability to survive against the antimicrobials designed to kill them,” said Akbankpe. “Antibiotic-resistant bacteria grow and take over, and they may also pass their resistance to other bacteria through the transfer of resistance genes. Resistant pathogens can continue to develop and spread to others, both in hospitals and communities.”
The causes include over prescription; self-medication; overuse in livestock and fish farming; patients not finishing the treatment; poor post-infection control; lack of hygiene and sanitation; and, the lack of new antimicrobials.
“Unfortunately, the current arsenal of antimicrobial treatments has not evolved to deal with new resistant strains and the pipeline of new antimicrobials needed to contain AMR is in decline,” said Agbankpe. “Antimicrobials take 10 to 20 years to develop with high R&D costs – many developers are going bankrupt or exiting the market. We need policy makers to acknowledge the growing problem and to create a drug pipeline.”
It’s also important to find therapeutic alternatives which currently include monoclonal antibodies, probiotics and bacteriophages.
Natural killers
“Phages are the most interesting,” said Agbankpe. “They are a type of virus that appeared at the same time as the first bacteria and are found wherever bacteria are. They play a major role in the functioning and balance of the ecosystem.”
“Phages are viruses that infect bacteria and attack only single bacterial strains – this specificity together with their killing capacity makes them the natural enemies of bacteria,” he added.
Agbankpe explained that phages have two types of lifecycles – lysogenic, which does not take control of host metabolism, and lytic, in which DNA is injected into bacterial cells and takes control of their metabolisms.
“Phages attach themselves to the surface of bacterial cells, infect the host cell by injecting its DNA, the viral DNA takes over the bacterial DNA and produces new phages. The new phages are then released by lysis of the host cell.”
Phages have been used as therapeutic agents for over 100 years. French-Canadian microbiologist Felix d’Herelle first observed bacteriophage phenomenon in 1910 and in 1917 began testing them in humans – for example, administering them to a 12-year-old boy for dysentery resulting in recovery. “They were abandoned with the advent of antimicrobials but are now regaining attention. But the phage-therapy pipeline is long and needs funding and patience.”
“Phage therapy is more development in Europe and the USA with dedicated research centres and products already available – but they are not yet used in Africa,” he added.
Agbankpe, who is originally from Benin but now based in Guinea, explained the research he has been involved in in this rapidly growing field.
“Our involvement in a project with Pakistani collaborators with funding from The World Academy of Science and the Islamic Development Bank looking at the potential severity of AMR resistance in COVID-19 and phage-assisted biocontrol enabled the development of the first phage research laboratory at the University of Abomey-Calavi in Benin. This involved master’s and PhD students and post-docs and involved the isolation of 47 different phages from samples taken from wastewater, effluent and sewage.”
A fellowship funded by the African Research Excellence Fund along with his STIAS fellowship then allowed Agbankpe to go to the Leicester Centre for Phage Research where he spent nine months characterising and learning about the morphology of all the phages isolated and testing the bacterial activity of some of the phages confirming them as good candidates for therapy.
He then set up a research team at the Unit of Bacteriology, Institut Pasteur of Guinea where they are developing phage cocktails to increase antimicrobial activity and evaluate the efficacy of such cocktails. The hope is to carry out the first clinical trials within five years.
But he pointed out that there are major challenges in Africa including the lack of a regulatory framework for phage-based products which makes it difficult to progress to development and discourages investment. “We don’t have the regulatory framework to go to human trials. Funding is also not the same as in other parts of the world.”
“There are also capacity problems in Africa – it’s hard to attract limited science graduates. Funding has helped us a lot to keep our research teams together.”
He also highlighted socio-cultural perceptions and acceptance. “There is a strong distrust of innovative therapies and a low level of awareness among both health professionals and the public. There are stigma associated with the use of viruses as therapeutic agents which hinders acceptance.”
“We are trying to engage policy makers to resolve the regulatory issues. We are also trying to do community outreach. But it’s a long process. The establishment of the African Phage Forum in 2021, which aims to promote scholarship, collaboration and mentorship, is an important step to advance phage research in Africa. It’s an attempt to bring the research together and have one voice and also, hopefully, will make it possible to approach larger continental organisations like the African Union.
“But it’s hard to convince anyone without good data from Africa.”
Michelle Galloway: Part-time media officer at STIAS
Photograph: SCPS Photography