The Emergence of Novel Pathogens: The Greatest Risk of Hubris in Human Health

Authors: Chan Harjivan, Anthony Ho and Shabana Farooqi

PwC Response to the WEF Case Study: 'Dangers of Hubris on Human Health'

Over the last century, humanity has made tremendous progress in the fight against infectious diseases. As a result, the majority of the world’s population now enjoys a significantly longer and better quality of life. In fact, the strides made in public health are recognised as a key driver of economic growth worldwide, improving productivity and increasing life expectancy.[1]

Remarkable advances in the life sciences and innovations in healthcare have enriched our ability to overcome an increasing variety of public health challenges. Yet, despite these new capabilities, humanity still remains ill-equipped to combat emerging infectious diseases. Ironically, human progress is partially responsible for our increasing vulnerability to novel pathogens. Like other threats to humanity, we have the ability to do something about it, if we act in tandem.

We are forcing the accelerated evolution of infectious disease

The public health community should be proud of its accomplishments, but there is danger in complacency. We simply cannot afford to assume that drugs we use today to treat infections will always work, or that they are a panacea for future infectious diseases. In fact, as Figure 1 illustrates, the armamentarium of drugs that are presently used to treat common infections have become less effective over time as the pathogens naturally develop resistance. Those people unfortunate enough to experience a drug-resistant infection are typically left with few treatment options. These typically involve costly second and third line therapies, and only if those resources are available to the patient.

Figure 1 - Timeline of antibiotic deployment and the evolution of antibiotic resistance

Source: Timeline of antibiotic deployment and the evolution of antibiotic resistance. Clatworthy A.E., et al. Targeting virulence: a new paradigm for antimicrobial therapy. Nature Chemical Biology. 3,541-548(2007)

To truly capture the extent of the drug resistance issue, it is important to first understand that antibiotic resistance applies only to the therapeutics used to treat bacterial infections. Here we take an expanded view of the overarching threat of antimicrobial resistance (AMR), which encompasses all pathogens against which antimicrobials are used such as bacteria, virus and fungi. Additionally, we recognise that the overuse of antimicrobials is a key factor in the development of resistant pathogens, albeit only one part of a reinforcing combination of new factors that speed up incidence of antimicrobial resistance.[2]

Three factors are providing the primary catalysts for the evolution and emergence of novel pathogens:

  • Massive overuse and misuse of antibiotics, in clinical, agricultural and environmental settings, overexposes pathogens to current antimicrobials.
  • Increased contact between human and animal populations has created an environment where pathogens are readily passed between species – a global mixing bowl of pathogens.
  • Genetic engineering and synthetic biology provide the ability to custom-build microbes; including novel man-made pathogens. 

These new catalysts have created an environment that allows common infectious microorganisms to more quickly and easily acquire mutations, making them deadlier and able to spread rapidly. This environment is fostering a massive acceleration of Darwin's natural selection.

Governments, the life science industry and healthcare providers have all begun to address AMR and are aware of each other’s efforts, but they are not yet coordinated and integrated. Given the broad and global range of the new catalysts for AMR, we need synchronised multi-sector and multinational collaboration to slow down its development. For collaboration to be successful, not only must it span public and private actors, but it must also involve partnerships and incentives that reach across the continuum of care. This includes detection of novel pathogens and disease trends, development of more efficacious antimicrobials and delivery of healthcare services and medicines efficiently.

To begin, organisations must assess their role in responding to the challenge, understand their own susceptibility and vulnerabilities and recognise the potential opportunities and benefits available to them. Considering the global scale of the AMR challenge, we provide an effective, structured way to view the landscape of organisations, initiatives and interests that are discussed in a recent case study from the World Economic Forum. In this article, we discuss organisational incentives to help drive and sustain collaboration.

Description of the case

The World Economic Forum describes the emergence of antimicrobial resistance ( referred to as ‘antibiotic resistance’) as one of the most significant threats to human health, and one that is becoming more widely recognised as an urgent threat worldwide. The Forum emphasises this threat in ‘The Dangers of Hubris on Human Health,’ a case study in its Global Risks 2013 Report. Although the case study focuses on a specific type of AMR, antibiotic-resistant bacteria, the report authors paint an accurate picture of the consequences for down-playing or disregarding the threat of resistance: “...arguably the greatest risk of hubris to human health comes in the form of antibiotic-resistant bacteria.”

Public health experts and authorities around the world recognise that antimicrobial resistance is an enduring threat – one not likely to go away anytime soon. Despite effective new treatment options or the wisdom and knowledge from past experience - and even with skills and tools drawn from advances in science and technology - the battle between humanity and disease is an unending ‘‘fight for survival.”

The infectious disease landscape is constantly changing, which is demonstrated by the discovery of new pathogens at an alarming rate of three per year.[3] Responding to the threat of novel diseases is an urgent area of need, which includes efforts to slow the emergence of resistant pathogens.  HIV, SARS and MERS should remind us that the threat of an unknown infectious disease is real, its transmission is unconstrained by social, economic or geopolitical borders, and it is potentially untreatable using any of the medicines that are currently available.

A 3-D response for the fight against antimicrobial resistance

What can be done?

The good news – global recognition of the problem has led to gradual increases in dedicated resources, focused efforts and strategic initiatives to address the problem. These include an improved antimicrobial product development pipeline, more timely and accurate disease surveillance and rational antimicrobial treatment and use policies.

The bad news – global recognition of the problem has led to the gradual increase in resources, efforts and initiatives that have not been coordinated to optimise impact. Given the breadth and diversity of approaches for addressing AMR, coordination and incentives are both key ingredients for building synergy between sectors, organisations and efforts. Figure 2 provides an overview of these approaches and illustrates the links between solutions.

Figure 2 - Identifying the problems and solutions

Source: PwC

Figure 2 presents an integrated view of several different approaches for preventing the emergence of AMR. The system of solutions is derived from a more basic framework, which provides individuals and organisations with a structured approach to evaluate roles, responsibilities, develop partnerships and pursue opportunities towards meeting their mutual goals.

The basic framework for practical implementation

As the WEF case states, “the problem can only be addressed through international cooperation.” Preventing the rise of AMR requires coordinated global action to enable the synergies needed to achieve greater levels of success. Current healthcare treatment policies incent the overuse of anti-microbial products. Like overfishing and global warming, use of antimicrobials faces the tragedy of the commons. We propose a structured perspective that provides a lens through which we can see and understand how the constellation of efforts and entities may be woven together to comprise a response (see Figure 3). Above all, the ‘glue’ needed to hold the framework together is appropriate stakeholder incentives.

Figure 3 - 3-D framework for implementation

Source: PwC

Our ability to successfully respond to this invisible global threat to public health depends on applying a more strategic approach as suggested by our framework. Doing so requires:

  • Collaborative stakeholder ecosystem – Successful response will inevitably involve an ecosystem of multiple stakeholders. This ecosystem encompasses a wide range of organisations that play an integral role in responding to the threat. At a high level, we have grouped these organisations into the following stakeholder communities: public sector, private sector and health care provider.
  • Comprehensive and balanced approach – The other dimension of our framework is the nature of the approach, which includes solutions that respond to Detection, Development or Delivery needs. Success isn’t just about the level of resources dedicated to each of these pillars, but how effectively the efforts are integrated.

Resilience practices

  1. Here we describe a set of resilience practices for countering the threat of AMR. Each practice is based on a separate pillar of the 3D framework and demonstrates how collaboration and incentives can be successfully combined to enhance capabilities for combating the spread and emergence of antimicrobial resistance.

    DETECT: Early warning systems and prompt intervention are essential to containing an outbreak and limiting potential loss of life and economic damage. The US$770 million losses in trade and tourism resulting from the cholera outbreak in Peru in 1991 and US$1.7 billion from the 1994 plague epidemic in India demonstrate how the damage can escalate if not tackled quickly and decisively.

    ‘Detect’ also requires the timely sharing and synthesis of information across an ecosystem of stakeholders, allowing them to understand and more accurately predict the emergence and impact of novel pathogens (e.g., virulence, at-risk populations, case fatality rate) and to trigger a timely response.

    Resilience Practice: The surveillance and detection of disease is a cornerstone of public health preparedness and a key capability that allows for rapid detection and analysis of public health trends. It yields data that helps organisations quickly recognise the emergence of a novel pathogen, prompting real-time action to contain transmission. Some organisations have even developed partnerships that effectively enable ‘predictive’ abilities. The partnerships facilitate interdisciplinary collaboration and support practical application of infectious disease modelling and pathogen discovery.

    Examples:
    • The WHO’s Global Outbreak Alert and Response Network (GOARN) is a technical collaboration of established institutions and networks, worldwide. The collaboration provides a centralised network into which partners can pool human and technical resources for rapid identification, confirmation and response to outbreaks of international importance.
    • The US National Institutes of Health and the US Department of Homeland Security have established an intergovernmental partnership that seeks to enhance the ability of researchers to anticipate and control outbreaks by working at the intersection of mathematics and the life sciences to establish scientifically-sound models to support outbreak forecasting and analysis. The programme, known as RAPIDD (Research and Policy for Infectious Disease Dynamics), is also designed to bridge the gap between academic findings and policy and decision-making.


  2. DEVELOP: Cross-sector and commercial collaboration such as product development partnerships, consortia and other innovative business models are responsible for growing the R&D pipeline of new candidate antimicrobial therapeutics, as well as preventative healthcare products like vaccines. While these partnerships address a somewhat altruistic public need, they also involve the necessary incentives that make them practical. The strategies used by these stakeholder communities support the innovation needed to bolster the armamentarium of antimicrobial products and tools available to combat novel pathogens.

    Resilience Practice: As a major driver behind the accelerated development of innovative new medical products, partnership, portfolio and operational strategies have helped organisations develop, acquire and market therapeutics, vaccines and diagnostic products. These strategic interventions also contribute to better products, more effective tools and faster product cycle times.

    Examples:
    • The Pistoia Alliance is an international consortium of private and public sector organisations focused on developing standards and tools. Here, partners collaborate by sharing pre-competitive R&D data to lower relative risk and cost to each partner while increasing the likelihood that a licensed product would emerge from the consortium.
    • A Public-Private Partnership (PPP) between the University of Medicine and Dentistry of New Jersey, the biotechnology company Cepheid Inc. and the Swiss-based non-profit Foundation for Innovative New Diagnostics (FIND) led to the development of a WHO-endorsed automated diagnostic test for tuberculosis. Through this partnership, each partner organisation was able to individually achieve more by working as a team and identifying the right incentives such as negotiating lower manufacturing costs to significantly reduce price and increase access to the technology.[4]


  3. DELIVER: A successful response to the problem of antimicrobial resistance requires a combination of factors that apply to the delivery of healthcare. To optimise impact, stakeholders must align and coordinate their efforts. This is especially important in making sure that antimicrobial drugs and diagnostic kits are both accessible and available around the world, that the use of antimicrobials is both responsible and judicious, and that governments and organisations establish effective infection prevention and control policies.

    Resilience Practice: Changing our own behaviours can have the greatest impact on how fast antimicrobial resistance develops. This requires encouraging judicious use of antimicrobials through rational use policies and full compliance with prescribed treatment, reduced usage in animal agriculture and increased infection prevention and control practices, amongst others.

    Examples:
    • Better supply chain management can improve the consistency and availability of drugs. Identifying and mitigating supply chain risks can avoid improper usage and maintain efficacy of low-cost treatments. For example, The Global Fund has a Pharmaceutical Procurement and Supply Management Plan and drives supply chain risk mitigation efforts associated with the anti-malarial drug programme.
    • Thailand’s ‘Antibiotic Smart Use’ programme has become a working model for how a country can promote the rational use of antimicrobials in clinical settings to reduce the incidence of resistance. This has been a multi-phased effort focused on modifying the prescribing practices and usage behaviours of health professionals and patients.
    • Efforts driven by healthcare providers include establishing formal, structured programmes such as the Hospital Antimicrobial Stewardship Program (AMSP). Here, the programme manages the incidence of infection through regular assessments and active surveillance; all practices endorsed by the US Centers for Disease Control and Prevention. Incentives here include lower patient readmission rates, which translates to lower costs to the provider, while also decreasing the incidence of hospital-acquired infections – a common source of infections by drug resistant pathogens.

Caused by anybody, solved by everybody

The medicines we use to treat infectious diseases are becoming increasingly less effective. Unchecked, we risk regressing to a state where we can no longer fend off common infections, let alone novel hospital superbugs, viral pandemics, and even genetically-engineered microbes. Humankind has brought about the three major key contributing factors to antimicrobial resistance:

  • The undisciplined use of antimicrobials in clinical settings and their overuse in animal agriculture.
  • Novel pathogens emerging as a result of increased human mobility and the frequency of interspecies contact due to urbanisation and changing environmental conditions.
  • Our expanding technological capabilities also create an enabling environment for microorganisms to more readily and rapidly acquire mutations that can transform them into more resistant and malicious creatures.

We have demonstrated that synergy and shared knowledge help organisations recognise and possibly modify current behaviours. By collaborating to coordinate initiatives and programmes, and by identifying shared incentives, they increase the likelihood of success, sustainability, and resource savings.


[1] Antimicrobial Resistance (AMR) applies to a wide variety of micro-organisms that predominantly include bacteria, fungi, virus, parasites, and protozoa.  Resistance implies that the microbe has developed immunity to antimicrobials to which they were originally susceptible.
[2] Institute of Medicine (US) Forum on Microbial Threats. Washington (DC): National Academies Press (US); 2009.
[3] Bloom, David E., David Canning and Jaypee Sevilla. "The Effect of Health on Economic Growth: A Production Function Approach." World Development 32, 1 (2004): 1–13.
[4] Foundation for Innovative New Diagnostics (FIND) website. Accessed via http://www.finddiagnostics.org/about/what_we_do/successes/find-negotiated-prices/xpert_mtb_rif.html.