Ethiopia’s antibiotic footprint: estimate of national antibiotic consumption using 2018 data

The processes involving resistance development against antibiotics have historically been part of the Darwinian evolution. But in the backdrop of this evolutionary reality, the increasing use of antibiotics in modern medicine, particularly in post-penicillin discovery era, has intensified the selection pressures with an acute gear up rather than as part of the so slow and natural evolutionary process that selects for enhanced fitness for survival. Two major recommendations were made in the past years to tackle this challenge: 1) incentivizing the pharmaceutical industry to invest more on research and development endeavors, so that they come up with new and novel antibiotics; 2) implementing antimicrobial stewardship programs in healthcare systems. In the current study, the third and the emerging approach — the idea of antibiotic footprint — was employed as a communication tool that targets individual consumers of antibiotics to tackle the problems of their misuse and overuse. A total of 698.2 tons of antibiotics were used in Ethiopia in 2018, and the per capita consumption of antibiotics was 5.8 grams per person. Penicillins with extended spectrum (J01CA) and beta-lactamase-resistant penicillins (J01CF) were the most commonly utilized classes of antibiotics which accounted for, respectively, 38.3% and 20.8% of all antibiotics used in the country’s public health sector. Hubs in Addis


Background
Historical records on man's conscious understandings about infectious diseases and their causative agents are centuries old. In the 14th century for instance, two notable Persian scholars, IbnKhatima and Ibn-al-Khotib, proposed that infectious diseases were caused by what they called "contagious entities" [Varley et al], but without definitively describing what those "contagious entities" were. Moreover, using antiinfective agents obtained from natural products are widely engrained in the practices of traditional medicine in many ancient cultural societies. For instance, analytical investigations which employed mass spectroscopic techniques in recent times obtained evidence from human skeletal remains in ancient Nubian civilization (dating back to 350-550 AD) which revealed that the antimicrobial tetracycline extracted from Streptomyces bacteria in beer fermentation was used for the treatment of infectious diseases [Nelson et al].
Fast forward, particularly since the period commonly called 'the scientific revolution' (ca 1500-1800) marked by the emergence of modern science, sustained efforts had been underway to discover cure for infectious diseases. A number of chemical entities were synthesized in laboratories as part of such scientific endeavors. The major limitations of the chemical entities synthesized in such laboratories had not however been efficacy, but safety. For example, Salvastan, an anti-syphilis synthesized in 1910 by Ehrlich and in fact the first antibiotic ever made by man in the laboratory was too toxic to make it to the clinical catalogue. Penicillin was the first safe and efficacious antibiotic discovered in laboratory, by the Scottish scientist Alexander Fleming and his co-workers in 1928, and came to clinical use during the Second World War [Watt & Collee] and in fact because of it.
The series outbreaks of infectious diseases in Europe during and right after the end of second World Warthe primary victims of which being wounded soldiers during the warfurther boosted the scientific endeavors made to synthesize more effective antibiotics in laboratories. In fact, all of the scientific investigations that ultimately brought penicillin, hitherto forgotten on the Petri dishes of Alexander Fleming's Lab for over a decade, were centrally coordinated and funded by government research agencies and scientific wings of army departments which were in desperate need for anti-invectives for soldiers who sustained wounds in the war [Quinn]. Over the two decades that followed, such momenta were kept as commercial companies and governments in Europe, Japan and North America continued funding scientific researches. As a result, new classes of antimicrobial agents developed one after anotherleading to what is now commonly called the 'golden age' of antimicrobial chemotherapy [Saga & Yamaguchi, Gould].
Over the last seven decades, antimicrobial chemotherapy constituted humanity's effective strategy to fight infectious diseases with remarkable gains that significantly However, evolution is challenging these gains of antibiotic revolution in modern medicine. The processes involving resistance development against antibiotics have historically been part of the Darwinian evolution. But in the backdrop of this evolutionary reality, the increasing use of antibiotics in modern medicine, particularly in post-penicillin discovery era, has intensified the selection pressures with an acute gear up rather than as part of the so slow and natural evolutionary process that selects for enhanced fitness for survival [Julian, Jose, Charles].
Two major recommendations were made in the past years to tackle this challenge.
One is incentivizing the pharmaceutical industry to invest more on research and development endeavors, so that they come up with new and novel antibiotics The concept envisages to stimulate behavioral changes practically needed to reduce individuals' direct and indirect consumption of antibiotics in communities. Adopted from the already established innovative concept of "carbon footprint" and aspiring to build on its successes, "antibiotic footprint" quantifies consumptions of antibiotics in human health, in animals/livestock and in agriculture/aquaculture (see conceptual  The goal of carbon footprint is to reduce the use of energy generated from fossil fuels and hence emissions of greenhouse gases to a minimum [GFN] and likewise, the goal of antibiotic footprint is to reduce antibiotic consumption to a minimum by cutting their unnecessary use [MARU]. The underlying idea is that we have to use energy to live, but using too much energy obtained from fossil fuels is driving climate change which has become an existential threat to human survival on planet earth. Likewise, we have to use antibiotics to fight infectious diseases in humans and in animals, but overuse and misuse of antibiotics is promoting resistance and hence increasing the number of people and animals dying due to infections caused by drugresistant strains of bacteria.
The current study aims to employ this emerging concept of antibiotic footprint to estimate the gross and per capita consumption of antibiotics in Ethiopia for the year 2018.

Materials and methods
Disaggregated data depicting the utilization of antibiotics at all the regional hubs of  In 2018, a total of 698.2 tons of antibiotics were used in Ethiopia, of which a little more than three quarters accounted for the use in human health (Fig 2). tons (1.9%), respectively (Fig 3).

Fig 4 Quantities of antibiotics ( in tons)
consumed at EPSA's regional hubs in 2018.

Discussion
In this study, the newly emerging concept of antibiotic footprint was employed to The distribution of disaggregated data for antibiotic consumption at the regional hubs (for human health) appear to resonate well with the patterns of population settlement density in Ethiopia (see Fig 4 below), and hence its subsequent pressure on the demands for healthcare service provisions. The study is not however without its limitations. First, the data for the consumption of antibiotics in the livestock sector used in the current study were not primary data as were the case for those in the human health sectorthis being due to lack of complete and compiled data availability for the former in Ethiopia's official registers. For the data in the livestock sector, we therefore had to rely on documented scientific projection figures, i.e., secondary data, offered by expert consultants at Precise Consult International [PCI] in which they did estimate the annual consumption of antibiotics in Ethiopia for the year 2018 based on the 2012 data. This means that the quality our data on antibiotic consumption for the livestock sector are only as good as secondary data could be. Second, our data for annual antibiotic consumption in the human health did not include antibiotics used within the private health sectoralso due to lack of complete and compiled data. Official reports show that the private health sector in Ethiopia accounts for some 27% of the total number of healthcare facilities available in the country [private sector], and hence if we assume that the sector could possibly account for same proportion in the total annual consumption of antibiotics in the country, this might have had an effect of a downward biasto that extenton our estimate of Ethiopia's antibiotic footprint for the year 2018.

Conclusion
As has also been suggested elsewhere, the concept of antibiotic footprint is such a suitable tool for communications targeting individual consumers of antibiotics in the community. If implemented judicially, it can support global scientific efforts in setting standards which help to reduce the overuse and misuse of antibiotics in the futureboth in the human and in animal health sectors.