Antibiotic resistance is the quintessential One Health issue

Abstract

In May this year, the long-awaited final report from the Review on Antimicrobial Resistance was published. 1 The report estimates that the 700 000 annual deaths currently attributable to infections by drug-resistant pathogens will increase, if unchecked, to 10 million by 2050, running up a bill of US$100 trillion in terms of lost global production between now and then. The reported numbers are somewhat apocalyptic, as they are based on crude projections of current trends and presume the failure of anti-malarial drugs and antiretroviral therapy as well as antibiotics. Nor do they account for the possible entry of new drugs onto the market. There is huge uncertainty associated with the human burden of antimicrobial resistance (AMR) in general and antibiotic resistance in particular (for the purpose of this article the widely used term antimicrobial resistance [AMR] is retained, though the emphasis here is on antibiotic resistance). The precision of the estimates does not really matter much: the point is that the problem is already immense and is growing rapidly. We have been squandering our antibiotic resources for far too long and immediate action is needed on a very large scale if we are to reverse current trends. It is difficult to imagine an issue that epitomises the principles of One Health more than AMR does. The One Health approach, defined as ‘...the collaborative effort of multiple disciplines – working locally, nationally, and globally – to attain optimal health for people, animals and our environment…’, 2 recognises that the health of people is connected to the health of animals and the environment. AMR has clear links to each of these three domains. The contribution of animal production, both terrestrial livestock and aquaculture, to the global AMR crises is questioned by some on the grounds that we don't see so many animal-associated infections in humans. 3 While this may be true, because of the way that many antibiotics are used in animal production, in sub-therapeutic doses and with long exposure periods, these production systems create ideal conditions for bacteria to fix genes that confer resistance. These genes can subsequently be transmitted to human-adapted pathogens or to human gut microbiota via people, contaminated food or the environment. They also provide ideal conditions for the amplification of genes that may have arisen in people or the environment. The fact that the antibiotics used in human and animal health largely comprise the same or very similar molecules would be expected to drive the transmission of resistance between animals and people, either directly or via the environment. Of the three domains, human health takes the spotlight, with multidrug-resistance genes now highly prevalent in many important and common pathogens like Escherichia coli , Klebsiella pneumoniae and Staphylococcus aureus. Quite apart from the many infectious diseases for which we rely on antibiotics to combat, these drugs underpin modern medicine by allowing us to carry out common surgical procedures and treatments that depress the immune system, such as chemotherapy to treat cancer. The global burden of AMR on the population has been estimated, 1 , 4 and more specific studies have also been carried out; for example, the estimated 214 000 neonatal deaths attributable to resistant sepsis infections globally in 2013; 111 523 occurring in the five countries with the highest numbers of neonatal deaths in the world: India, Pakistan, Nigeria, Democratic Republic of Congo and China. 5 Such estimates of the burden of AMR have not been attempted for livestock or aquaculture, perhaps due to a perceived lower importance. Resistance to antibiotics among mastitis pathogens, for example, is well documented though it is not considered to be an emerging or a progressing problem. 6 Recent estimates of the amount of antibiotics consumed in livestock production conservatively place this at 63 151 tonnes in 2010. 7 The situation is less clear in aquaculture. 8 Although actual figures are currently unavailable, the published estimates of the proportion of antibiotics consumed in animal agriculture—84% (for 36 antibiotics) in China 9 and 70% in USA 10 —suggest global agricultural consumption probably exceeds that of humans. A large part of this use is justified and valid on veterinary grounds, 6 but there is much misuse in the agricultural sector. With such large consumption levels it seems likely that agricultural use contributes significantly to AMR. A recent review suggested that misuse of antimicrobials in animal production is a clear and substantial driver of AMR, 11 and there is a growing body of evidence linking antibiotic consumption in livestock to AMR in the clinic. 12 Many infections in people are endogenous; derived from the human gut flora. An important gap in knowledge relates to the possible extent and mechanisms of transmission of antibiotic resistance genes between the normal gut flora of animals and that o