Microbial evolution and the threat of antimicrobial resistance, by Dr Ismail Muhammad Bello
Microbial evolution and the threat of antimicrobial resistance by Dr Ismail Muhammad Bello You must have heard of climate change, an existential threat to humanity and one that requires a synergistic global action. Well, that is not the only one. Antibiotics resistance is another that is emerging at an alarming rate. It was not very long ago when the pathological basis of diseases was unknown and believed to be superstitions. About 400 years back, the role of microbes in disease causation was not known. It took the discovery of microscope and the works of Antoni Van Leeuwenhoek to open our eyes to the unseen world – the World of microbes – which surround and live in us.
Microbes are ubiquitous and have evolved dramatically to survive in a highly dynamic world. The human relationship with microbes is vast and interesting. Thanks to their versatility, microorganisms play a crucial role in human technological advances through their varying applications in agriculture, environmental protection, medicine, and industrial production. From drugs discovery and development to their application in bioremediation, biotechnology as well as the newer genetic engineering, microorganisms have contributed tremendously to the survival and advancement of life forms on earth and even moulded civilizations.
However, despite their monumental importance to the earth’s operations, microbes contribute to human misery as pathogens. Despite the rising incidence of non-communicable diseases, infectious diseases are a problem worldwide especially in Sub-Saharan Africa where we are faced with a double burden of diseases – an increasing prevalence of non-communicable diseases in the face of yet-to-be-conquered communicable diseases.
Beyond the high mortality and morbidity rates caused by infectious diseases, the burden includes economic losses due to care for diseases and disabilities but also as a lack of productivity. More generally, infectious diseases impede human development by their negative impact on education, income, life expectancy and other health indicators.
Although the numbers are still considerably high, the case was different a long time ago as certain infections that are relatively easily curable now were death sentences before or very difficult to treat. The remarkable and accidental discovery of Penicillin by Alexander Fleming is one of the greatest milestones in the history of medicine. Not only did “Antibiotics” make many diseases easily curable, along with discoveries in anaesthesia, major surgeries have become safer and more feasible.
The word antibiotics may have a more specific definition in a class of pharmacology but as it is commonly known, it refers to a group of drugs used in the treatment of “bacterial” infections. Bacteria is only a class of microorganisms, others include viruses, fungi, parasites and even prions. Antibiotics work by inhibiting crucial processes in the microbes which results in their inability to maintain their structural integrity or functional capacity thereby making them die or arrest their replication.
This category of drugs includes the famous Amoxicillin, Metronidazole (Flagyl), Ciprofloxacin, Amoxiclav (Augmentin) amongst many others that are easily obtained over-the-counter in our setting. Antibiotics have played crucial roles in combatting menacing diseases like Tuberculosis, Leprosy, Gonorrhoea, Syphilis, bacterial pneumonia, meningitis amongst many others.
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The advent of these drugs came as a huge blow to the pathogenic microbes that were hitherto having a free day. But as natural selection suggests, they would not go passively without a fight as they sensed the development as a declaration of war. These microbes gradually evolved over the years to become insensitive to many of these drugs – a concept known as “Antibiotics Resistance”.
In response, the scientists discovered new drugs, tweaked some of the existing drugs or synthesized new ones. This led to a vicious cycle whereby as new drugs are developed, these organisms adapt to them and become resistant. That has continued to our present time and led to the emergence of highly resistant strains of microorganisms that are not susceptible to most of the antibiotics used in treating the kind of infections they cause – the so-called Super bugs.
Unfortunately, this cycle is not sustainable for mankind. The rate at which microbes adapt to our drugs is faster than the turnout of our drugs. It takes about 10-15 years to develop a new antibiotic. Not only that, but research have also shown that the estimated global cost of developing a new, targeted antibiotic will cost over a billion USD making it a highly expensive venture.
The combination of these factors has slowed down innovation in antibiotics. The latest discovery of a new antibiotic class that has reached the market was back in 1987. Since then, there has been a lack of innovation in the field, and today there are few novel antibiotic classes in the drug pipeline. In 2019, WHO identified 32 antibiotics in clinical development that address the WHO list of priority pathogens, of which only six were classified as innovative. The consequences are seen worldwide as more and more bacterial infections are becoming hard to treat once again posing a threat to global health and development.
Unarguably, resistance is a natural phenomenon and will eventually develop to any antibiotic, but the rate at which it is occurring is aided by our irrational use of these drugs therefore prudent use will surely slow down the process. Some of the important determinants of antibiotics resistance include antibiotic abuse in veterinary and medical practice, inadequate provision of Water, Sanitation & Hygiene (WASH) infrastructure, effective policy development and/or enforcement.
Abuse of Antibiotics
Abuse of antibiotics entails their overuse and misuse. Medical professionals, unskilled health personnel, veterinary practitioners, animal farmers and individuals in the community are all culpable in this harmful practice. While in humans, antibiotics are used mainly for therapeutic purposes, in veterinary practice antibiotics are used greatly for non-therapeutic purposes like growth promotion to catch up with the increasing demand for animal protein worldwide. Even for therapeutic purposes, a common practice is administering antibiotics sometimes even at a level below the therapeutic dose to entire herds when only some animals are ill for “disease prevention”.
The environment occupies a strategic place in the evolution and spread of antibiotic resistance. Waste from large-scale animal farms, use in aquaculture and wastewater from antibiotic manufacturing, hospitals and municipalities are major sources of antibiotic resistance genes and antibiotic pollution in the environment. Parts of the antibiotics given to humans and animals are excreted unaltered in faeces and urine. Such waste from animals’ manure is rich in nutrients and is often used as fertilizer on crop fields, leading to direct contamination of the environment with both antibiotic residues and resistant bacteria.
In human medical practice, the lack of adherence to standard treatment guidelines has resulted in the unjustified prescription of antibiotics by medical professionals. A common occurrence is the prescription of antibiotics for non-bacterial conditions like the common cold. Medical professionals are also guilty of prescribing these drugs below the standard treatment dosage or for a shorter duration, especially at the primary level of healthcare. Such practices expose the organisms to a sub therapeutic level of the drugs which is nonlethal, thereby making them develop resistance.
Along this line, health professionals must be continuously trained on the appropriate use of antibiotics and adherence to standard treatment guidelines in disease management. Health institutions equally should have antibiotic stewardship programs to systematically educate and persuade practitioners on the effective utilisation of these drugs. Physicians’ responses to patients’ treatment expectations are also an important cause of inappropriate antibiotic use. Efforts should be channelled towards patients’ education rather than succumbing to patients desires and pressure.
Outside the hospital, many practices continue to fuel this problem. Such practices are common in developing countries where most drugs are gotten over-the-counter and drug vendors are not necessarily knowledgeable in drugs and diseases. From Flagyl to Meropenem, drugs could be obtained without prescriptions making these endangered drugs that demand protection easily accessible.
This ease of accessing drugs has opened the floor for self-treatment or “chemist” consultation where malpractices are indulged in. Again, a recurring situation is prescribing antibiotics for the common cold. Studies have shown that the common cold is caused mostly by viruses which are not treated with antibiotics. It is a self-limiting condition treated with steam inhalation and antihistamines e.g., loratadine, and decongestants.
Like the common cold, most cases of sudden onset of the passage of watery non-bloody & non-mucoid stool with or without vomiting is of viral aetiology. This is usually self-limiting and requires no antibiotics more often than not. Especially in children, the cornerstone in the management of diarrhoea is fluid therapy using Oral Rehydration Solution (ORS). Drug treatment is rarely of any use, and antidiarrheal drugs are often harmful. Sadly, most people are quick to take a dose of Flagyl and “Diastop” within the first bout of diarrhoea.
Bloody or mucoid stool, high fever, severe abdominal pain, and prolonged diarrhoea are pointers to more serious conditions that may warrant antimicrobial use and should be quickly evaluated by a qualified doctor.
Another problem that continues to fuel this issue is the highly prevalent & bewildering “Malaria-Typhoid diagnosis.” Lack of clinical skills needed to appropriately discern acute febrile illnesses and high request for the obsolete Widal test is leading to a high rate of a strange “Malaria-Typhoid diagnosis.” Most cases are of sudden onset of high-grade intermittent fever that is worse in the evening, associated with generalised body weakness and pain with no symptoms attributable to the gastrointestinal system. In a region where malaria is quite prevalent, this most likely suggests a case of simple Malaria that should be managed as such. Strangely in our setting such cases are quickly subjected to Malaria and Typhoid (Widal) tests at the request of a healthcare worker or even on self-referral.
Research have shown severally that the Widal test is not highly specific especially in endemic zones like ours where repeated exposure to the bacteria is common. Cross-reactivity with many other diseases like Malaria – another common cause of fever in Nigeria, as well as difficulty in interpretation, are some other factors that make its usefulness as a reliable diagnostic indicator very limited. It is therefore obvious that the overreliance on the Widal test has led to overdiagnosis of Typhoid fever and consequently antibiotic misuse. It is also this practice that has led to the wrong notion of “chronic typhoid” among gullible persons. Typhoid fever is not in the league of HIV & HBV. Infection in typhoid does not persist infinitely but could recur especially when the risk factors remain.
Though not an antibiotic, antimalarials continue to receive their share of misuse. A wrong practice that is quite common is the over-utilisation of parenteral antimalarial drugs, commonly IM arthemeter. Nowadays people are quick to seek injections simply because “I don’t like swallowing drugs, or it works faster or better.” Unfortunately, such drugs are reserved for the treatment of a severe form of malaria which someone that walks to a chemist surely does not have. This action is tantamount to deploying the elite special forces for a minor case of crime. It is expected that these forces should only be mobilised for a significantly heightened threat or when the threat has escalated beyond the capacity of the initial responders.
Way Forward
The government occupies a strategic position in this battle. Policies & regulations must be put in place towards ensuring effective utilisation of these drugs. As it has been our major problem, these policies should not remain as documents in offices but must be enforced strictly and punishments meted to defaulters. Such regulations will cover a range of issues including the use of antibiotics in veterinary practice and food production, proper regulation on the opening and operation of patent medicine stores.
Prevention is certainly better than cure. Tackling infectious diseases at the primary level is more impactful and cost-effective. The Covid-19 pandemic has highlighted the importance of Water, Sanitation and Hygiene (WASH) in disease transmission & control. Hand hygiene – an act that many have learned in 2020 – is the most important measure to prevent the spread of infections. It is therefore important that portable water and adequate sanitary infrastructure are provided to communities to forestall the propagation of these diseases in our society.
For every ailment, there is a standard treatment guideline that prescribes what drugs, when and how to use them. Treatment protocols should be developed by hospitals based on their peculiarities, circulated widely and strictly adhered to by practitioners. Also, practitioners should take time to counsel patients on the importance and risks of adherence to the prescribed dosage and duration of treatment. Antimicrobial stewardship should be adopted to ensure effective utilisation and surveillance of resistance patterns in these hospitals.
This is a battle declared by the microbial world on humanity, thus everyone has an important role to play. Individuals should seek effective medical advice on diseases and treatments and shun resorting to self-help.
So, when you take antibiotics for a simple common cold, know that you may be endangering humanity. When you fail to complete your antibiotics for the duration prescribed, you are endangering humanity. Even when you treat typhoid when it is not the culprit, you are harming the patient and the world at large.
Finally, this is a battle for all of us. Let us all be antibiotics advocates. Let us all use these assets judiciously to prevent a time when no drugs could cure Pneumonia, Syphilis, or Meningitis.
Ismail Muhammad Bello is a Medical Doctor, (House Officer) at Yobe State Specialist Hospital, Damaturu. He can be reached via email: ismobello@gmail.com .
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