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Ebola outbreak exposed the risk of pandemic and need for globally coordinated response, DARPA plans for Rapid Development of Medical Countermeasures

From Ebola outbreak in West Africa to various strains of avian influenza to, most recently, the rapid spread of Zika has shown that even with all advances in modern medicine we are still not completely safe from pandemics. These  epidemic of infectious diseases  can spread quickly through human populations across a large region several continents, or even worldwide

Since the first reported case in December 2013 in Guinea, the Ebola outbreak quickly spread to bordering Liberia and Sierra Leone ravaging West Africa.As Bill Gates warned at the Munich Security Conference, millions of lives are at risk and the economic consequences pale in comparison to other global threats. Last Ebola outbreak cost more than 11,000 human lives and more than $32 billion in economic ripple effects while Zika has cost the economies of Latin America and the Caribbean an estimated $18 billion. In addition to these naturally occurring threats, terrorists and other potential adversaries have a growing palette of biological tools to engineer new biological threats.

As the bipartisan Blue Ribbon Study Panel on Biodefense highlighted, U.S. levels of readiness and global coordination are woefully inadequate.  Warfighters must also operate in regions where diseases like chikungunya and dengue are endemic, and even seemingly mild challenges like seasonal influenza affect force readiness.  The threat of infectious agents on U.S. and global national security can be mitigated if the Department of Defense (DoD) has the capability to rapidly deploy and impart near immediate immunity to military personnel and civilian populations for known and newly  emerging pathogens.

Eliminating pandemic outbreaks and mitigating the impact of a potential high threat biological agent release are national security priorities. The U.S. military supports U.S. Government responses to public health emergencies such as Ebola, which can cause regional destabilization and spread through global travel, says DARPA.

DARPA has issued a new broad agency announcement (“BAA”) seeking proposals to support the creation of an integrated “capability platform” for the delivery of medical countermeasures to prevent a pandemic threat within sixty days of targeting a known or newly emerging pathogen.

Risk of pandemics

The Global Challenges Foundation had released report that found pandemic as one of the 12 global risks that threaten human civilization. “There are grounds for suspecting that such a high impact epidemic will have a greater probability than usually assumed. All the features of an extremely devastating disease already exist in nature: essentially incurable (Ebola), nearly always fatal (rabies), extremely infectious (common cold), and long incubation periods (HIV). If a pathogen were to emerge that somehow combined these features (and influenza has demonstrated antigenic shift, the ability to combine features from different viruses), its death toll would be extreme”, says global challenges report.

Scientists estimate that between 1940 and 2004, 335 new infectious diseases appeared in humans. This number includes pathogens that likely entered our species for the first time, such as HIV, and newly evolved strains of familiar organisms, such as multidrug-resistant tuberculosis. The majority of these diseases—about 60 percent—were caused by zoonotic pathogens, meaning they were transmitted to humans from animals. And of those, about 70 percent were from animals that typically live in the wild.

These include HIV and AIDS, influenzas (including pandemic H1N1, H5N1 and H7N9), Severe Acute Respiratory Syndrome (SARS), Middle East Respiratory Syndrome-Coronavirus (MERS-CoV), Ebola, Marburg, and Nipah. Several of these have spread extensively in human populations to cause a global epidemic (also known as a pandemic).

Ran Balicer, director of the infectious diseases track in the public health department of Ben Gurion University in Israel, thinks that the most likely candidate for another pandemic is a strain of influenza. “It is always on the horizon, and is a devastating scenario,” he said. “It has a good possibility of manifesting in our lifetime; there have been three major pandemics, and a mild one three years ago – which doesn’t reduce the possibility of a pandemic happening.”

If antibiotic resistance develops, humanity could see the resurgence of bacteria-based pandemics.

Factors that impact severity and probability

Christophe Fraser, a professor of epidemiology at the medical research council center for outbreak analysis at Imperial College, London, described four factors that are crucial in determining how severe an epidemic will be: how easily the disease is transmitted; how feasible it is to develop a vaccine and a treatment; how long before symptoms are visible the patient is infectious; and the severity of the disease – what proportion of people who contract it die.

The” Lancet Global Health: Beyond Ebola: lessons to mitigate future pandemics” says, Increasing anthropogenic environmental changes, coupled with a globalised network of travel and trade, allow zoonotic pathogens to spill over into human beings with increasing frequency, and leave us supremely vulnerable to their international spread.

 

Five important factors in estimating the probabilities and impacts of the challenge:

1. The pandemic risk lies in the probability distribution at the “tails” – the extreme events – and these tails must be estimated from few data points, making them tricky and uncertain.
2. The capacity of modern international health systems to deal with an extreme pandemic. The inadequacies of the health-care systems in the three most-affected countries help to explain how the Ebola outbreak got this far. Spain spends over $3,000 per person at purchasing-power parity on health care; for Sierra Leone, the figure is just under $300. The United States has 245 doctors per 100,000 people; Guinea has ten.
3. How fast medical research can proceed in an emergency.
4. How mobility of goods and people, as well as population density, will affect pandemic transmission.
5. Whether humans can develop novel and effective anti-pandemic solutions.

 

Expected Impact

Pandemics are one of the risks where there is a possibility for a very large number of direct casualties, depending on the severity of the pathogen. Mass casualties could destabilize the world political and economic systems. If the pathogen is transmissible to farm animals, this could affect the world food supply.

Hence the risk of a civilisation collapse would come from the ripple effect of the fatalities and the policy responses. These would include political and agricultural disruption as well as economic dislocation and damage to the world’s trade network (including the food trade).

The World Bank Group released a report in April 2015 showing that the Ebola epidemic continues to cripple the economies of the three hardest-hit countries—with a projected $2.2 billion in lost GDP for 2015. Estimated economic losses for 2015 across sub-Saharan Africa range from at least $500 million to as high as $6 billion if the epidemic were to spread further through the region.

Ebola isn’t our first wake-up call that pandemics are costly. From 1997-2009, six major outbreaks of highly fatal zoonoses—animal-borne diseases that can be transmitted to humans, such as Ebola, SARS, avian and H1N1 flu—caused an estimated $80 billion in economic losses. The human and social costs are incalculable.

Extinction risk is only possible if the aftermath of the epidemic fragments and diminishes human society to the extent that recovery becomes impossible before humanity succumbs to other risks (such as climate change or further pandemics).

What would mitigation strategies to deal with future pandemic risks?

The” Lancet Global Health: Beyond Ebola: lessons to mitigate future pandemics” says, “Pandemics are no longer simply the domain of public health and clinical medicine, but are a social issue, a development issue, and a global security issue.
Mitigation of future pandemic threats such as Ebola is more cost-effective than the current approach of responding to outbreaks after they have begun to spread rapidly in the human population.

Analyses of emerging disease trends during the past six decades have shown that Ebola fits the dominant pattern. This pattern involves zoonotic spillover from wildlife or livestock driven by changes in land use, crop choices, migration patterns, animal husbandry, trade, transport, and travel.

Global mitigation of future pandemic risk must focus on the largescale behaviors that lead to zoonotic spillovers. This approach means engaging with the sectors that drive disease emergence, including industries involved in land-use change, resource extraction, livestock production, travel, and trade, among others.

Various countermeasures are available in terms of detection, virus analysis, treatment, and quarantining. Future research, technological and political developments may open up new methods of fighting the pathogen.

The improvements to surveillance and sensing technologies (including indirect detection via web queries or social media) open the possibility of smarter interventions (such as microquarantines) and faster understanding of the pathogen’s transmissibility.

The efficiency of global reaction to a new pandemic will be strongly determined by the speed of research on the pathogen during the pandemic. The acceleration of vaccine development for Ebola as part of an outbreak control strategy could also have a crucial role to mitigate future outbreaks.
Ebola’s propensity for nosocomial spread could be curtailed by pre outbreak vaccination of critical care workers in Ebola virus hotspots. Likewise, targeted training in infection control, and efforts to maintain surge capacity between outbreaks, will be crucial for rapid response to the first cases in a future emergence event.

DARPA Seeks to Establish New Platforms for Rapid Development of Medical Countermeasures

Existing capabilities to respond to an outbreak and develop vaccines and therapeutics often take years or even decades to achieve results. The R&D process for identifying the protective antigens can take months for a simple variant of a known infectious agent, such as seasonal influenza, and years to decades for a newly discovered agent. In many cases, even decades of research have not led to the development of licensed vaccines for known infections.

Further, manufacture of traditional vaccine products typically takes an additional six to nine months. Finally, even when effective vaccines are readily available, immunity in humans can take weeks or months to establish.

Recent examples of public health emergencies have demonstrated a national and global inability to develop effective preventive or therapeutic solutions in a relevant timescale when an infectious threat emerges. Reviews of recent outbreaks have repeatedly highlighted this capability gap; the significant delay in deployment of solutions during the West Africa Ebola outbreak is a recent example.

The goal of the Pandemic Prevention Platform (P3) program is to develop an integrated capability to deliver pandemic prevention countermeasures to humans in <60 days. The P3 program aims to revolutionize outbreak response capabilities to allow rapid discovery, characterization, production, and testing of efficacious medical countermeasures.

 

Proposed approaches under the DARPA BAA must be capable of meeting three primary objectives.

On-demand platform to grow virus: First, proposed approaches must be capable of rapidly producing viruses in sufficient quantity for countermeasure development from discovery through testing, potentially by growing viruses in engineered cell types or through similar rapid processes. Although the BAA targets pathogens generally, successful offerors will be expected to work with viruses in performing contemplated activities.

System to evolve antibodies: rapid creation of highly potent medical countermeasures: Second, proposed approaches must be capable of rapidly producing high-potency antibodies or other proposed biological products, with an expectation that offerors will likely identify an in vitro antibody maturation platform. Although DARPA is willing to consider a range of biological products that target particular viruses—including other proteins, peptides, and oligonucleotides—the BAA assumes that antibodies will be used to ensure rapid countermeasure development.

Delivery of medical countermeasure(s): reproducible effects which lead to protective levels of product.

Third, proposed approaches must identify delivery methods that are designed to induce in animal models complete protection against a targeted pathogen within three days, ideally following a single administration using a method that can be employed in austere conditions and with a protection period lasting more than thirty days.

Using computers for Epidemic prediction

Zoonotic disease outbreaks occur when a virus, bacterium, or fungus jumps from an animal to a human. Maintaining active disease surveillance around the world is costly and time-consuming, accurate prediction of when and where these infections will occur next can enable us to better mitigate these outbreaks before they become epidemics.

Barbara A. Han, PhD, disease ecologist at Cary Institute of Ecosystem Studies, Millbrook, New York, and her colleagues built a computer program to analyze a massive database of mammalian habits and habitats, including the geographic range and reproductive strategies for hundreds of species and used it to predict which of the 2,277 existing rodent species will serve as zoonotic disease carriers in the future and where they are likely to spread diseases. Their model considered 86 variables, like body size, life span, and population density, to hunt for patterns common among animals known to carry zoonotic diseases.

Han said in a press release. “We were interested in how machine learning could inform early warning surveillance by revealing the distribution of rodent species that are effective disease reservoirs.” Based on its findings, the team was also able to identify hot spots where a disease was more likely to jump from rodent to humans, Kansas, Nebraska, China, Kazakhstan and parts of the Middle East are potential hotspots.

USC Viterbi School of Engineering Ph.D. students Charalampos Chelmis and Anand Panangadan and computer science Ph.D. candidate Ajitesh Srivastava earn national recognition for forecasting outbreaks. They produced a prediction model that uses information sharing to accurately deliver a six-month forecast of the spread of the Chikungunya virus in 55 different countries and territories in North, Central and South America and the Caribbean.

“Information sharing on the Internet is based off of information sharing on epidemics, so we took that and applied it to predicting outbreaks,” Srivastava said. “It’s a similar method to the process of assessing how a meme or a video goes viral.” DARPA began the CHICKV Challenge in 2014 to create models that could accurately predict the spread of Chikungunya.

Need for Pandemic Emergency Facility

Fraser said that the current outbreak of Ebola has shown that the global systems that are supposed to spot outbreaks of diseases are not good enough, “and more importantly, the action that follows is not fast enough, not coordinated enough, to cut off an epidemic at source.
Although existing multilateral agreements (eg, the International Health Regulations) allow for some coordination of national responses to outbreaks and bilateral interventions to build public health capacity in poor countries, more is needed.

The Ebola crisis and other similar crises point to the need for prevention, preparedness, early detection and timely support to help countries deal with infectious disease outbreaks. Financing for a pandemic emergency is essential—to ensure that the right amount of money is available at the right time, minimize the human and economic impacts, and spur better preparedness. The better prepared, the faster and less expensive our response. In a world of scarce resources and fast-moving, unpredictable crises, the traditional approach of mobilizing resources in the wake of an outbreak is slow, inefficient and fragmented.

The World Bank Group (WBG) is working with WHO and other partners, including the private sector, to develop and implement a new Pandemic Emergency Financing Facility (PEF). The PEF is a global financing facility that would channel funds swiftly to governments, multilateral agencies, NGOs and others to finance efforts to contain dangerous epidemic outbreaks before they turn into pandemics.
Post-pandemic politics will also be important for preventing a civilisation collapse or enabling reconstruction.

 

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