Advancing Planetary Health in Australia: focus on emerging infections and antimicrobial resistance

Animal reservoirs

The severe acute respiratory syndrome coronavirus (SARS-CoV) outbreak in 2003 highlighted the importance of animal reservoirs as a source of human infection. Henipavirus outbreaks, including Hendra on the Australian eastern seaboard and Nipah in Malaysia and Bangladesh, demonstrated the importance of bats as viral reservoir species and of domestic animals (horses and pigs, respectively) as amplifying hosts.9 For the Middle East respiratory syndrome coronavirus (MERS-CoV), domestic camels have been implicated as the likely amplifying hosts.10 Fortunately, serological testing of camels in Australia, which is home to the largest population of wild camels in the world, has revealed no evidence of MERS-CoV infection to date.11 Bats may also carry Ebolavirus, but its environmental reservoirs remain uncertain.12 In general, the inter-relationships between animal reservoirs and amplifying hosts, as well as the circumstances that lead to pathogen overspill or backspill between wildlife, livestock and humans are poorly characterised.13

Pathogen surveillance

In the absence of systematic pathogen surveillance in wildlife and domestic animals, human cases often act as sentinel events that alert public health officials to a new infection of animal origin. Even when animal disease surveillance detects unusual signals, communication with human public health networks is often suboptimal, as illustrated by the West Nile virus outbreak that swept across the USA.14 The risk of infections spreading from wildlife reservoirs into human populations is exacerbated by the expansion of agriculture and mining into natural environments, road infrastructure, deforestation, subsistence hunting and co-location of wild and domestic animals in so-called wet markets. Strategically, targeted surveillance of the environment, domestic and wild animals, infection vectors and vulnerable human populations will facilitate early detection and better control of disease emergence risk.15

The importance of pathogen surveillance has been emphasised by both the Ebola Interim Assessment Panel chaired by Dame Barbara Stocking16 and the Independent Panel on the Global Response to Ebola chaired by Professor Peter Piot.17 The Stocking report recognised poor implementation of International Health Regulations (IHR), which were approved by the World Health Assembly in 2005, as well as the need for global solidarity to build local capacity, which has been incorporated in target 3.d of the SDGs: ‘Strengthen the capacity of all countries, in particular developing countries, for early warning, risk reduction and management of national and global health risks’. IHR implementation requires strong government commitment to establish and maintain public health laboratory and service provider capacity. The US committed US$1 billion towards the Global Health Security Agenda,18 while the UK created a £1 billion fund in partnership with the Bill and Melinda Gates Foundation to tackle malaria and other infectious diseases.19 The Australian government committed $A300 million over 5 years 2017–2022 to the Indo-Pacific Centre for Health Security,20 assisting core capacity strengthening and complementing WHO’s regional strategy for emerging diseases and public health emergencies in the Asia-Pacific (Asia Pacific Strategy for Emerging Diseases; APSED III 2017).21

Mechanisms of disease emergence

The synthesis of data on the ecology and evolutionary biology of various organisms provide enhanced understanding of pathogen emergence, but information on the social mechanisms that underpin disease outbreaks and persistence remains rudimentary. For example, the reasons for increasing rates of human non-typhoidal salmonellosis in Australia (noted at the workshop), at a time when rates were falling in most comparable countries, were poorly understood. Integration of food, animal and human surveillance data could provide the insight needed to improve control of these infections. The impact of climate change, particularly on water and vector-borne diseases, was highlighted as a key concern. Viruses spread by Aedes aegypti and A. albopictus mosquitoes (Zika, dengue and chikungunya) pose a significant risk to global health. So far, Australia has successfully restricted these mosquito populations, but the likelihood of their permanent establishment will increase with climate change.22 Mosquito surveillance in Australia is undertaken on a state-by-state basis with coordination by the National Arbovirus and Malaria Advisory Committee. More comprehensive and better standardised surveillance programmes will facilitate accurate mapping of mosquito populations and better tracking of endemic and imported viruses.

The ‘invisible man’

Presymptomatic or asymptomatic individuals can unwittingly spread infection. Salient examples include the spread of HIV from asymptomatically infected individuals, the 48 hours presymptomatic period during which patients with influenza are infectious and unrecognised colonisation with multidrug-resistant organisms. Outbreak control strategies usually depend on syndromic diagnosis and cluster identification to guide intervention strategies. When outbreaks are fuelled by unrecognised human vectors, the importance of routine infection control precautions becomes evident and pre-emptive control measures such as quarantine of high-risk individuals or large-scale social distancing may be appropriate. Such measures are difficult to implement. Risk assessment and modelling to predict the most likely eventualities in advance and develop realistic scenarios to aid public health response preparedness are important to guide mitigation strategies.

Key barriers and proposed solutions

Strengthening of public health systems, especially in low-income and middle-income countries, is essential to achieve core IHR capacities. The Australian Government’s Health for Development Strategy 2015–2020 articulated most of the important elements required for a comprehensive regional response,23 but Australia’s international aid budget has declined to its lowest level in many decades; falling well short of international targets.24 Effective implementation of the joint external evaluation process in the Asia-Pacific region has provided a valuable overview of country-level preparedness, but it needs to be combined with the World Organisation of Animal Health (OIE) Evaluation of Performance of Veterinary Services assessment to improve One Health surveillance, while ongoing monitoring is essential to ensure that identified capacity gaps are addressed and best practices shared.24 25

It is predictable that EIDs will escalate in frequency. Although much effort has been expended in developing pandemic preparedness policies, recent experiences with SARS and MERS-CoV demonstrated that even the most advanced medical systems require continued vigilance linked to careful scenario response planning.25–27 Epidemic outbreaks, or even the perceived threat of an epidemic, usually lead to a flurry of activity, but lessons learnt and interim policies developed are rarely consolidated during interepidemic periods. Successful policy implementation requires an expert panel that represents all relevant disciplines, to work with the Commonwealth Office of Health Protection to draft national guidelines and monitor implementation of actions to reduce the likelihood and negative impact of EIDs. It could also oversee the drafting of generic research proposals to test interventions and generate enhanced insight during epidemic outbreaks.

Methodologies for better decision-making during emergencies require refinement.28–30 The Rockefeller-Lancet commission identified three important strategies, adopting a threshold approach, scenario planning and resilience thinking. These require pre-emptive scoping of relevant risks, as well as possible scenarios and outcomes associated with identified courses of action. Effective public communication in times of uncertainty poses a major challenge. The Australian media were more measured than media outlets in the USA during the 2014 Ebola virus outbreak, but news reports still generated considerable public anxiety. Detailed scenario planning will help to identify priority actions and communication strategies to reassure the public that the situation is under control and that perceived risks are manageable. Optimal communication will require close liaison between researchers, public health officials (for human, animal and environmental health), policymakers and the media.

Within Australia, there is no formal framework within academic institutions or government to facilitate and support cross-disciplinary collaboration, although the National Framework for Communicable Disease Control does encourage a One Health approach to pandemic preparedness.31 Increased AMR awareness has been encouraging,32 33 but like climate change progress is slow, given the multiple vested interests and differences in risk/benefit perception. Much can also be learnt from the roadmap developed by the US Centers for Disease Control and Prevention (CDC) to assist One Health operationalisation.34 The Australian National Antimicrobial Resistance Strategy 2015–2019, jointly developed by the Departments of Health and Agriculture and Water Resources, represents an example of how these silos can be linked,35 but implementation remains challenging.

Antimicrobial use in production and companion animals

The ecological effects of antimicrobial selection pressure, including its effects on the human and animal microbiome, are poorly understood. Antimicrobial use in production animals has been restricted in Australia following the recommendations of the Swann report.36 When avoparcin use in feedlot cattle was shown to increase the prevalence of Enterococcus faecium resistance to vancomycin (a glycopeptide antibiotic used for the treatment of human infections),37 it was voluntarily withdrawn from the Australian market. Fluoroquinolones were never approved for use in production animals in Australia, which probably explains the low levels of fluoroquinolone resistance observed in Campylobacter, Salmonella and Escherichia species compared with other countries where agricultural use is unrestricted.38 39 Globally, the pork and chicken industries are the biggest users of antimicrobials.40 Recent descriptions of highly resistant bacteria found on chicken and swine farms in China, linked to outbreaks of human infection with bacteria containing similar plasmid-mediated resistance, offer a stark example of the health risks associated with unregulated antimicrobial use in production animals.41 42 However, it was acknowledged that the responsible use of antimicrobials to address concerns about food security and animal welfare require careful consideration.

Companion animals are important to Australians; 63% of households own pets and the pet industry contributes nearly US$4.75 billion to the Australian economy, employing 45 000 people.43 The health benefits of pet ownership are estimated to save the healthcare system approximately US$2.25 billion per year.44 Despite the intensity of interaction, there has been surprisingly little research into the transmission of AMR between pathogens of humans and their pets. A better understanding of antimicrobial use in companion animals is needed, since there is no regulatory guidance and pets fall outside the agriculture and health portfolios.

Antimicrobial stewardship and public education

Australian doctors prescribe more than twice the amount (in defined daily doses per 1000 population per day) of antibiotics compared with their counterparts in the Netherlands.45 At least 30% of prescriptions are judged by experts to be clinically inappropriate, inadequate or unnecessary. Litigation risk aversion, diagnostic uncertainty, time pressure and perceived patient demand are among the reasons why doctors overprescribe antibiotics.46 Evidence of previously unrecognised harm related to impacts on the human microbiome, as well as the social and ecological harm from AMR, should inform development of novel strategies to optimise antimicrobial use. A public policy research agenda, informed by social scientists and psychologists, should explore how best to reform policy settings, devise appropriate incentives and disincentives, develop innovative public and professional education programmes and use social media to improve public understanding and influence responsible regulation expectations. Both the general public and professional groups require an enhanced appreciation of basic infection control principles.

Key barriers and solutions proposed

Based on scenarios of increasing AMR prevalence for six pathogens, it has been estimated that by 2050, 10 million lives per year and 100 trillion USD of economic output may be lost due to AMR infections.33 A divisive debate has focused on the relative impacts of human versus animal or agricultural use of antimicrobials, but constructive collaboration is essential to elucidate and mitigate the key drivers of AMR. A major advance in promoting a One/Eco Health approach to AMR in Australia was achieved through the joint support of the Australian Chief Medical and Veterinary Officers to develop and implement a National AMR Strategy. This is the first joint ministerial initiative between the Australian Government Departments of Health and of Agriculture and Water Resources.

The WHO’s Antimicrobial Resistance: Global Report on Surveillance (2014) identified a policy package with broad goals that included strengthened surveillance and laboratory capacity.47 However, without adequate funding and accountability measures, such farsighted policies will continue to fall short, especially in the Asia-Pacific region where antimicrobial use is essentially unregulated and strong financial incentives exist to retain the status quo. The WHO Western Pacific Region’s Action Agenda is a step towards tackling these problems, but the agenda includes no plans for effective stewardship.48 Lack of funding for cross-disciplinary research was identified as a significant barrier; participants believed that this was exacerbated by the separation of the two major Australian public research funding bodies—the National Health and Medical Research Council (medical) and the Australian Research Council (non-medical). Breaking down traditional medical, veterinary and biological research silos is crucial, with dedicated funding to support cross-disciplinary initiatives.

Few new antimicrobials have been developed in recent years, as antimicrobials do not deliver attractive returns on investment.33 Private–public partnerships have been used with success to develop vaccines for neglected diseases,49 but this requires generous philanthropic support. New economic models should reward antimicrobial discovery (or novel non-antibiotic approaches to reducing AMR) as a public good, delinking the return on investment from the volume of sales. The Association of British Pharmaceutical Industries Antibiotics Network has suggested an insurance-based model that guarantees an annual license fee, providing a more predictable return on investment.50 While the development of new antimicrobial drugs is important in the short term, history has shown that resistance will develop in response to selection pressure and spread without appropriate infection control measures. Alternative therapeutic strategies, such as bacteriophage treatment may be successful if linked to rapid and accurate pathogen identification. Attempts to reduce selection pressure fuelled by indiscriminate microbial killing, includes highly targeted bacteriophage-based approaches, modification of disease causing microbes to make them more susceptible to immune attack and developing strategies that prevent or selectively treat invasive disease only. Rapid point-of-care tests that differentiate viral and bacterial infections, and provide antimicrobial susceptibility profiles, would assist more targeted use of conventional antibiotics.