Dan Scott | Health Science Correspondent
Antimicrobial resistance is not a new phenomenon. Antibiotics, for instance, are chemical warfare agents synthesised by bacteria, fungi and protozoa which constantly evolve for their continuity, fitting as a snug exemplar to Darwin’s “survival of the fittest” hypothesis.
Following the discovery of penicillin in 1928, healthcare was revolutionised after successful treatment after treatment to cure life-threatening diseases with a “wonder-injection” alongside manageable side effects. Cue a huge international quest for more potent, specific antibiotics. Antibiotics then found a huge place in livery stock for a more stable food supply: copious amounts were added to milk in particular to prevent bacterial spoilage.
In April of this year, the World Health Organisation (WHO) declared the entrance into the “post antibiotic era” in their annual Antimicrobial Resistance Global Report on Surveillance.
It’s without surprise that when backing an infection-causing microbe into a metaphorical corner, it’s going to put up a fight. Hence forth, the quick-fix wonder treatments began to fail as germs smartened up and twiddled with a gene or two to ensure survival. In April of this year, the World Health Organisation (WHO) declared the entrance into the “post antibiotic era” in their annual Antimicrobial Resistance Global Report on Surveillance. Few new antibiotic drugs are in the pipeline. The treatment of MRSA (methicillin resistant staphylococcus aureus), vancomycin is beginning to fail evolving into VRSA (vancomycin resistant staphylococcus aureus) slowly in the past decade, leaving fewer avenues for treatment. Antibiotic prescribing guidelines issued to practitioners regard the use of augmentin as a second line treatment option (amoxicillin, the antibiotic which prevents bacterial wall growth and clavulanic acid, an enzyme inhibitor which blocks the breakdown of the antibiotic by the bacteria) failing the use of the antibiotic on its own.
I stress the word antibiotic, as this does not encompass the treatment of fungal or viral infections, the latter of which has sparked media interest following the Ebola outbreak in Western Africa. In the most recent WHO report, 4293 cases and 2296 deaths were confirmed as of the 8th September with an estimated 83% case fatality rate. Throughout the last ten to fifteen years, emerging contagious fatal diseases mostly come in a viral form: SARS, H5N1 avian and H1N1 swine flu to name the most infamous, sparking media explosions and international panic as there is “no cure” or a vaccine in development is only in trials. Viruses are also the main cause of a dry cough, sore throat and the flu. Being a pharmacy student, many friends and family joke at how I could develop the next blockbuster drug for cancer, with the “there’s no cure for the common cold” pub fact often cropping up. Many also tell me about how great it is to pick up antibiotics over the counter in Spain as it works for every ailment (which, for the record, it doesn’t).
In the most recent WHO report, 4293 cases and 2296 deaths were confirmed as of the 8th September with an estimated 83% case fatality rate.
With the Ebola epidemic, is there scope for a new strain to form?
“It’s highly unlikely that a new species of Ebolavirus (EBOV) could form during the current outbreak but as EBOV has a single stranded, negative sense RNA genome it can mutate relatively easily. There is evidence from a recently published Science paper that the current virus is mutating but the significance of those mutations is not yet known” explains Dr. Kim Roberts, Ussher Assistant Professor of Virology in the Department of Microbiology at TCD.
ZMapp is the controversial, experimental Ebola treatment that has been given to a small number of high profile sufferers in the western world but yet to undergo human clinical trial. It is a monoclonal antibody cocktail which shows the most promise within the development pipeline. In simple terms, mice are infected with the virus, and the antibodies that they produce are harvested. The antibodies that are most effective at blocking the virus are humanised and administered for treatment. Although monoclonals are traditionally challenging and very expensive to manufacture, genetic engineering developments have allowed a scale up of the ZMapp antibodies to be grown in the tobacco plant following viral infection. Speaking on the topic of potential resistance, Dr. Roberts describes:
“The ZMapp product is composed of 3 monoclonal antibodies that target different, non-overlapping regions of the viral glycoprotein and this should reduce the risk of escape mutants occurring. [However], whilst prolonged use of ZMapp in an infected person may generate escape mutants this does not mean that the escape mutant viruses would then be transmitted to new hosts.”
Other routes to treatment include vaccines currently in development which would allow the host to develop an immune response to the virus, however these are only due to enter phase I clinical trials next month and be in a position for trial in the most affected countries by the new year. A huge challenge following the development of these therapies is formulation and storage. Most require refrigeration to prevent degradation or else are freeze-dried with thoroughly sterilised water added prior to administration. Intravenous injection is the only route available for delivery which requires specialist training and also causes pain in the patient. While these may seem relatively easy to deal with in a developed country such as Ireland, in the most Ebola stricken countries such as Guinea, Liberia and Sierra Leone, refrigeration through transport and storage, medical training and sharps waste for needles is not as easy to come by, making treatments incredibly challenging.
Other routes to treatment include vaccines currently in development which would allow the host to develop an immune response to the virus, however these are only due to enter phase I clinical trials
The microneedle system has been proposed as a popular solution to this issue. A small patch of miniscule spikes loaded with drug or freeze dried vaccine particles often made of silicon act by penetrating the skin’s impermeable layer (stratum corneum) and allow a route of drug delivery to the small blood vessels which are abundant within the dermal layer. Particles simply diffuse into the bloodstream and nerve endings are not affected, thus no pain involved. Although many global efforts are made in this direction, one particular research group in Ireland with an exciting future has developed the multi-patented ImmuPatch. Affiliated between the School of Pharmacy at University College Cork and the Tyndall National Institute, both a dissolvable and solid microneedle patch has been developed by the group. Vaccine particles can be added to the liquid microneedle matrix before it is quickly spray dried to its mold at a relatively low temperature, ensuring the stability of the vaccine is intact. Products of this kind could be maintained at room temperature, meaning the issue of cold-chain storage is resolved, but further cost is saved without the need for sharps incineration as this is a needle-free technology. What’s more, due to the simplicity and low risk of the product, the ImmuPatch can be self-administered, making it a much more practical product in third world countries with limited medical resources.
Although we are facing a concerning future with regard to bacterial infections, the restrictions and scale up of more profound and economical anti-viral therapies show a direction in the right avenue.
