This Week in DC: Events

by Siddha Hover, posted in Events, Week In DC

A few events scheduled for today may be postponed due to the weekend snow – be sure to check event websites before heading out!

Monday, December 9, 2013
PeaceGame
US Institute for Peace
All day Monday – Tuesday afternoon

Governments around the world regularly devote enormous resources to conducting “war games.” On December 9 and 10, the U.S. Institute of Peace (USIP) and The FP Group (FP) will conduct the inaugural PeaceGame, with a focus on “the best possible peace for Syria.” With one game in the U.S. and another in the Middle East, the semi-annual PeaceGames will bring together the leading minds in national security policy, international affairs, academia, business, and media to “game” out how we can achieve peace in Syria. USIP and FP intend for the game to redefine how leaders think about conflict resolution and the possibility of peace.

Tuesday, December 10
Strengthening National Laboratory Commercialization
Information Technology and Innovation Foundation
10:00 AM

Post-World War II era U.S. science, technology, and innovation policy has been defined by a linear approach to public investment in basic research. For many decades, this worked because the United States was one of the few countries with the technological capabilities to translate research into new products and services. But in today’s intensely competitive global economy where nations are fiercely competing for innovation advantage, this paradigm is no longer tenable. Robust public investments in basic research remain critical, but equally as important are investments and institutional reforms to commercialize new ideas from the laboratory into the marketplace. To advance the debate on potential policy reforms, the House Technology Transfer Caucus, Co-Chairs Rep. Gus Bilirakis (R-FL) and Rep. Ben Ray Luján (D-NM), the Information Technology & Innovation Foundation, and Innovation Associates are convening a series of Capitol Hill briefings featuring leading experts in innovation policy.

Hearing: The Iran Nuclear Deal: Does It Further U.S. National Security?
House Committee on Foreign Affairs
1:00PM

Chairman Royce on the hearing: “I continue to have serious concerns that the agreement the Obama Administration negotiated does not meet the standards necessary to protect the United States and our allies. The deal does not roll back Iran’s nuclear program, but instead allows Tehran to keep in place the key elements of its nuclear weapons-making capability. Under the agreement, the international community relieves the sanctions pressure on Iran while its centrifuges continue to enrich uranium. This hearing will be an opportunity for Committee Members of both parties to press Secretary Kerry to explain why the Obama Administration believes this sanctions-easing agreement is the right course.“

The Transition in Afghanistan
Senate Foreign Relations
2:30PM

Witnesses: Ambassador James Dobbins, Special Representative for Afghanistan and Pakistan, U.S. Department of State; Mr. Donald L. Sampler, Jr. Acting Assistant to the Administrator, Office of Afghanistan and Pakistan Affairs U.S. Agency for International Development (USAID)

Wednesday, December 11
Squaring the circle: General Mark Welsh III on American military strategy in a time of declining resources
American Enterprise Institute
8:00 AM

With sequestration likely to remain law throughout this year and beyond, the US Air Force finds itself in a “ready today” versus a “modern tomorrow” dilemma. How will the Air Force balance capability, capacity, and readiness in the coming years? What is the future of key modernization initiatives such as the F-35 Joint Strike Fighter, the KC-46 aerial refueling tanker, and the long-range strike bomber? Moreover, what lessons has the Air Force learned from past debates that will influence upcoming budget proposals? In the concluding session of its series with the Joint Chiefs of Staff, AEI’s Marilyn Ware Center for Security Studies will host General Mark Welsh III, Chief of Staff of the US Air Force, to address these questions and more.

World Health Organization: Global media launch of the World Malaria Report 2013
National Press Club
9:30 AM

Malaria is one of the world’s most serious diseases, causing over 200 million infections and more than 600,000 deaths each year, mainly in children under five in sub-Saharan Africa. An estimated 3.4 billion people are at risk of the disease in almost one hundred countries, and need access to life-saving prevention tools, such as mosquito nets, and effective treatment. One week after the replenishment conference for the Global Fund to Fight AIDS, Tuberculosis and Malaria, during which international donors pledged 12 billion USD for the Fund, the World Health Organization (WHO) will launch its latest comprehensive report on the global effort to control and eliminate malaria. An annual scorecard, the World Malaria Report 2013 includes an assessment of trends in the scale-up of mosquito control tools, preventive therapies, diagnostic testing and treatment. It also reviews the global funding situation, the double threat of drug and insecticide resistance, as well as progress towards global targets set for 2015. WHO’s Dr Robert Newman will be joined by leading experts to discuss key findings of the report. The event will be moderated by former CNN journalist Jeanne Meserve.

Thursday, December 12
Critical Mass: Nuclear Proliferation in the Middle East
Center for Strategic and Budgetary Assessments
10:00 AM

At the briefing, the report’s author Dr. Andrew Krepinevich will provide his assessment of key security issues that may emerge in the event Iran acquires a nuclear capability, to include: the dynamics of a bipolar regional nuclear competition between Israel and Iran; the prospects for (and potential consequences of) a Middle East proliferation “cascade” involving other states in the region; the potential for a “Nuclear Great Game;” and the overarching challenges associated with preserving crisis stability and avoiding regional nuclear conflict. Dr. Krepinevich will also address why Cold War deterrence models may not apply to the nuclear competition in the Middle East, and why missile defenses may prove both destabilizing and cost-ineffective in this environment.

Joint Subcommittee Hearing: The Resurgence of al-Qaeda in Iraq
House Committee on Foreign Affairs
1:00PM

Witnesses: Kenneth M. Pollack, Ph.D., Senior Fellow, Saban Center for Middle East Policy, The Brookings Institution; Ms. Jessica D. Lewis, Research Director, Institute for the Study of War; Michael Knights, Ph.D., Lafer Fellow, The Washington Institute for Near East Policy; Daniel L. Byman, Ph.D., Professor, Security Studies Program, Georgetown University.

Friday, December 13
New Nuclear Suppliers
CSIS
9:00AM

Nuclear power is shifting East, and so too may nuclear suppliers. Nuclear energy long has been dominated by the West and by advanced economies, but this is likely to change in the next thirty years. While Japan’s nuclear industry is still reeling from the Fukushima accident, China, India, and South Korea have ambitious plans for nuclear energy at home and abroad. All three countries face capacity, regulation and financing challenges and all three have relatively little experience in export control harmonization. CSIS, with partners in India, South Korea, and China, explored the contours of responsible nuclear supply with key technical, official, and industry experts. Please join us for a discussion of our findings, and the results of our workshops in Delhi, Seoul and Beijing, with a distinguished panel of experts.

(image courtesy of Dell)

The Pandora Report 12.6.13

by Siddha Hover, posted in News, Pandora Report

Highlights this week include the second case of H7N9 in Hong Kong, WHO ramping up calls for increased surveillance for MERS, EEE in Vermont, why that one friend never gets sick, and the Philippines ramping up its biosecurity. Happy Friday!

Hong Kong sees second case of H7N9 bird flu in a week

Hong Kong has seen its second case of H7N9 in the last week. An 80-year old man with diabetes sought medical attention after experiencing minor heart failure, and within a couple days of hospitalization developed symptoms consistent with the flu virus strain. He has subsequently been isolated for further treatment – it remains unclear if he came into contact with poultry prior to his hospitalization. However, don’t freak out yet –  the two cases are consistent with expected resurgent flu numbers following the onset of winter. According to all literature and available case evidence,  the virus still cannot effectively transmit person-to-person.

South China Morning Post – “It was unclear whether the man had come into contact with birds and live poultry and which district in Shenzhen he lived in. The three family members coming with him to the city had been back in Shenzhen and the city had contacted the Shenzhen health authority for subsequent medical monitoring…Border checks have been stepped up after the first confirmed case, and three people, who stayed in the same ward as the helper but had had no symptoms, are being isolated at the Lady MacLehose Holiday Village in Sai Kung.”

WHO calls for action on Mers following death in Abu Dhabi

Earlier this week, a Jordanian woman infected with MERS died from the virus shortly after giving birth to her second child. Her eight-year old son and husband are both also infected, and are still under surveillance in Jordan. It is unclear if the newborn is also infected with the  virus. None of the family had any travel history, any prior contact with animals, or any contact with infected persons, further confounding public health officials trying to determine the virus’ vector. In response to the mother’s death, the WHO has strongly encouraged countries to ramp up their surveillance and monitoring efforts. To date, there have been 163 cases of the virus worldwide, with a case fatality rate of approximately 42% causing 70 deaths.

The National – “More must be done to stop the spread of the deadly Mers coronavirus, the World Health Organisation has warned. Countries must strengthen their surveillance, increase awareness and try to find out how people are infected, the WHO’s emergency committee said on Wednesday…But Mers-CoV is not yet considered an international public health emergency. ‘After discussion and deliberation on the information provided, the committee concluded that it saw no reason to change its previous advice to the director general,’ the WHO said. The 15-member committee, which includes the deputy health minister of Saudi Arabia, Ziad Memish, said the situation continued to be of concern, in view of new cases and of information about the presence of the virus in camels in Qatar last month. It called for more support for countries that are particularly vulnerable, such as Saudi Arabia – where most of the cases have been confirmed – and urged for more studies to investigate exactly how people become infected with Mers-CoV.”

Vt. testing deer samples to test for EEE virus

Biologists in Vermont have begun testing over 700 blood samples collected from local moose and deer in order to track the spread of Eastern Equine Encephalitis (EEE). The virus was first introduced to Vermont in 2011, following the importation of an emu flock. EEE is a zoonotic alphavirus virus which primarily affects horses. The virus’ natural reservoir is wading birds, and it is spread, like so many horrible diseases, by mosquitoes. Although in the US there are usually less than 15 human cases of EEE, the virus’ fatality rate can approach 60%. As an encephalitic virus, symptoms are typically nasty – first fever, splitting headaches, photophobia (aversion to light),  then irritability, coma, and death. Among those lucky enough to survive, the virus often causes permanent sequelae, including severe brain damage.

Seattle PI – “Biologists say that mapping where the virus is found will help broaden the state’s understanding of the spread of the virus — which killed two people in Vermont in 2012 and two horses this year. EEE antibodies detected in deer and moose have been found in every Vermont country. Biologists hope that by looking for antibodies in the deer and moose, they’ll be able to determine if infected animals are more commonly found near certain bodies of water or wetlands.”

A genetic defect protects mice from infection with Influenza viruses

Everyone has that one friend/relative/colleague who not only never gets sick, but also thinks the best time to discuss their fabulous immune system is when you’re knee deep in tissues and throat lozenges. It turns out there may be a genetic reason for their immunological smugness. According to a new study from researchers at the Helmholtz Centre for Infection Research (HZI) in Braunschweig, mice who possess a mutation in the gene which encodes for the Tmprss2 protease (a catalytic enzyme) are resistant to infection from the H1 influenza A viruses. While the virus still infects the mice, it is unable to produce mature, infectious virus particles, and the infection is quickly cleared from their symptoms. This opens up a potential new field for drug development, and by targeting the host system rather than the virus, concerns over drug-resistance fade.

Medical Express – “The virus uses haemagglutinin as a key to enter the host cell which is then captured to build new virus particles. To reach its final shape, the coating protein has to be cleaved by a molecular scissor. This is done by an enzyme of the infected host. Otherwise, the protein is not functional and the virus particles are not infectious. A variety of host enzymes, so-called proteases, that process the haemagglutinin have been identified using cell cultures. Scientists from the HZI have now been able to show how important those enzymes are for the progression of the infection. Mice with a mutation in the gene for the protease Tmprss2 do not become infected by flu viruses containing haemagglutinin type H1. They are resistant against H1N1, the pathogen responsible for seasonal influenza epidemics, the ‘swine flu’ and the ‘Spanish flu’, which caused an epidemic in 1918. ‘These mice do not lose weight and their lungs are almost not impacted,’ says Professor Klaus Schughart, head of the Department ‘Infection Genetics’ at the HZI.”

Philippine airports on alert for bird flu

The Philippines is on high alert for the H7N9 strain of avian influenza found in Hong Kong for the first time last week. Manilla has  banned the import of all Chinese poultry products, and  airports across the island nation already screen inbound travelers to prevent the virus’ spread. This is an interesting form of biosecurity, which is something we don’t often talk about on the PR, mostly because it’s not as much of a concern for us as our colleagues in say, Australia.In this instance, the human body itself is seen as the vector for pathogen movement, rather than a kiwi or tomato plant.

Xinhua – “The Philippine government has alerted airport authorities to ensure that the deadly bird flu H7N9 could not enter the country following the recent discovery of first case in Hong Kong, the Philippines’ Department of Health ( DOH) said Wednesday. To date there are 141 cases of bird flu and 47 deaths worldwide. Deaths were due to severe pneumonia with multi-organ failure. So far, two-thirds of bird flu H7N9 cases were males and two-thirds were more than 50 years old.”

(image via Hagerty Ryan, U.S. Fish and Wildlife Service)

H2N2 as a Potential Pandemic Threat

by Siddha Hover, posted in News

According to a new study published in the Journal of Virology, descendants of the H2N2 strain of avian influenza, last seen in humans in the 1950s, may still pose a significant threat to humans, particularly those under 50 years of age. According to the study, conducted by  St. Jude’s Children’s Research Hospital, the virus is still highly adapted to human respiratory cells. The last major outbreak occurred in 1957-58, and killed up to two million people globally. However, effective antivirals were absent at the time – should the virus, which has subsequently circulated in birds, re-emerge, it should be susceptible to modern antivirals. However, as the virus has not been seen in humans in over 50 years, anyone under the age of approximately 55 years would constitute a naive host, and as there are 230 million people in the US alone currently under the ages of 55, the size of this naive population is not insignificant. 

From Science Daily – “‘While these viruses genetically look very avian, this study shows they can behave like mammalian viruses and replicate in multiple mammalian models of flu,’ said the study’s first author, Jeremy Jones, Ph.D., a postdoctoral fellow in Webster’s laboratory. ‘That is troubling because some of the original H2N2 pandemic viruses looked avian when the pandemic began in 1957, but in a few short months, all of the isolated viruses had picked up the genetic signatures of adaptation to humans. Our results suggest the same could happen if the H2N2 viruses again crossed from birds into humans.’ Work is underway at St. Jude to identify other changes that are critical to the ability of avian flu viruses to infect and replicate in mammalian cells, Jones said.”

Read more here. 

(image via wikimedia commons)

Image of the Week: Evolution of Zombies

by Siddha Hover, posted in Images

This week’s image is this very cool infographic depicting the evolution of the zombie in film and video games.

the-evolution-of-the-zombie-infographic_529c57b52ed59_w1500via visual.y

 

H7N9 in Hong Kong

by Siddha Hover, posted in News

Hong Kong confirmed its first case of H7N9 yesterday, a 36-year old female who had previously travelled to mainland China and been in contact with poulty. The woman was admitted to Queen Mary’s Hospital last month, after falling ill. She remains in critical condition.

This is the second time the virus has popped up outside of mainland China, with a previous case in Taiwan early this year. Since February of this year, China has reported 137 cases of the avian flu, with 45 fatalities. However, it’s worth noting that while the virus does have pandemic potential, the majority of cases occurred last Spring, with less than ten cases total appearing over the summer and fall. Avian influenza viruses often behave similarly to seasonal flu viruses, with the majority of infections occurring in cooler months.

Prior to February, H7N9 had not infected humans. Labs in the US, UK, and Japan have all developed candidate vaccines.

(Image: James Jin/Flickr)

This Week in DC: Events 12.2.13 – 12.6.13

by Siddha Hover, posted in Events, Week In DC

The highlights of the free and open-to-the-public international security, terrorism, and policy events this week.

Monday, December 2
How the Global Order and the Modern State Empower Organized Violence
George Mason University School of Public Policy
7:15PM

Terrorists, human traffickers, insurgents, drug dealers, cyber criminals, pirates and other forms of organized violence, all actively exploit the separation that western societies and the international community try to maintain between what is considered “crime” and “war.” This separation, which is designed to promote stability and preserve liberty, is reflected in the very architecture, organizational and political cultures, and legal parameters assigned to law enforcement, judicial systems, and the military across western societies and within international institutions. However, insurgents conduct kidnappings by day and launch military-style raids at night as part of a holistic strategy that crosses traditional law enforcement and military boundaries. Pirates operate with impunity knowing that they are unlikely to be overtly attacked by navies on the high seas nor tried in a proper court upon capture. And drug lords, from Latin America to Los Angeles, challenge – and in some cases have virtually defeated – local law enforcement using high-end military weapons and tactics.

Tuesday, December 3
Cyber Conflict on the Korean Peninsula
Korean Economic Institute
10:30AM – 12:00PM

As the most wired place in the world, South Korea’s vulnerability to cyber threats is an important issue, especially when there are tensions with its neighbor to the north. South Korean banks, government agencies, media outlets, and businesses were all victims of cyber attacks and it is believed that North Korea was behind them. Many speculate that North Korea has units dedicated to cyber warfare and espionage. As a legitimate threat and provocation, it is important to understand the dynamics around cyber conflict on the Korean peninsula. Join KEI on Tuesday, December 3 as Dr. Steven Kim, Associate Professor at the Asia-Pacific Center for Security Studies in Honolulu, Hawaii presents his report on the cyber warfare tactics and strategies used by North Korea and the defense mechanisms employed by South Korea to prevent and deter cyber attacks.

Webinar on Environmental Security and Public Health
Elliot School of International Affairs
1:15PM – 2:15PM

Join us on the web December 3 for the third installation of a five webinar series on international environmental security, co-produced by the Security & Sustainability Forum and the National Council on Science and the Environment and led by experts from the Elliott School of International Affairs and the Stimson Center. Each webinar panel will examine a hypothetical scenario that could be a game-changer for national security, international business interests, political science theory, and our global environment. The panel on December 3 will examine the issue of the major threats to public health due to climatic and environmental change through a hypothetical scenario in which a new mosquito-borne disease emerges out of Africa or Asia. Please register for this ONLINE WEBINAR with the Security and Sustainability Forum at: go.gwu.edu/publichealth

Wednesday, December 4
FBI Agents to discuss National Security Issues
National Press Club
10:00 AM

FBI agents will discuss how sequestration’s mandated budget cuts are affecting daily FBI operations and hampering criminal and national security investigations, as well as the risks associated with additional budget cuts and furloughs expected early next year, at a National Press Club Newsmakers news conference on Wednesday, December 4. Leaders of the FBI Agents Association (FBIAA) will also update the group’s recent report Voices from the Field: FBI Agent Accounts of the Real Consequences of Budget Cuts. The report contains field reports from FBI Special Agents illustrating the impact of budget cuts on their work. Speaking at the Newsmaker news conference will be FBIAA President Reynaldo Tariche and several active duty FBI agents from around the country. This NPC Newsmaker news conference is scheduled to take place on Wednesday, December 4 at 10 a.m. in the Club’s Zenger Room, on the 13th floor of the National Press Building at 529 14th St. NW, Washington DC, 20045.

Subcommittee Hearing: Transition at a Crossroads: Tunisia Three Years After the Revolution
U.S. House Committee on Foreign Affairs
2:00PM

Chairman Ros-Lehtinen on the hearing: “Three years since the Arab Spring began, Tunisia is at a crucial crossroads in its democratic transition. The country has been enmeshed in a political stalemate, and growing internal and external security challenges further complicate the tenuous political process. A democratic Tunisia would not only be a model for other countries in this volatile region, but a failure to make this transition would have grave consequences for the security interests of the U.S. and other nations in the region. This hearing will examine the status of the transition and what the U.S. and other organizations are doing to promote democracy and civil society at this critical juncture in Tunisia’s history.”

Thursday, December 5
The Future of America’s Strategic Nuclear Deterrent
Center for Strategic & Budgetary Assessments
10:00AM

Although nuclear weapons have played a critical role in American defense strategy for more than 60 years, there is a growing debate over the number and type of nuclear forces that the United States actually needs to maintain its security and protect its allies. Over the past several years, calls for Washington to substantially reduce the size of its nuclear arsenal have become more prevalent, while the combination of declining budgets and looming recapitalization costs have made nuclear weapons a popular target for potential funding cuts. Please join us as CSBA releases its latest report, The Future of America’s Strategic Nuclear Arsenal, by Senior Fellow Evan Montgomery. At the briefing, Dr. Montgomery will address a number of issues: Can the United States implement deep reductions in strategic nuclear weapons and still deter rivals, dissuade competitors, and discourage proliferation? Should it retain the strategic triad of bombers, land-based intercontinental ballistic missiles, and nuclear-powered ballistic missile submarines? Finally, must it replace its aging nuclear forces?

Strengthening the NIST Cyber Framework Against Advanced Threats
CSIS
12:00 – 2:00 PM

The CSIS Technology and Public Policy Program invites you to attend Strengthening the NIST Cyber Framework Against Advanced Threats NIST’s Cybersecurity Framework has tremendous value for risk management and defines best practices to block known threats. This discussion will share intelligence about campaigns by sophisticated cyber threat actors that have targeted critical infrastructure companies and discuss how well the Framework stacks up against advanced and new, unknown threats. Lunch will be served.

The Effects of Funding on Scientific Productivity: The Case of Academic Chemistry, 1990-2009
GMU Technology, Science, and Innovation Policy Research Seminars
12:00 – 1:30PM

This month’s seminar will feature Joshua Rosenbloom, of the National Science Foundation. This monthly seminar series, sponsored by George Mason University’s Center for Science and Technology Policy (School of Public Policy), explores new ideas and work-in-progress with the Washington-area research community. It’s open and free to all interested researchers with a special invitation extended to graduate students. The seminars are held at the George Mason University’s School of Public Policy (Founders Hall) on the Arlington campus, a short walk from the Orange Line’s Virginia Square/GMU Metro stop. CSTP will provide coffee and cookies — participants are welcome to bring a brown bag lunch.

Can the U.S. and China Build a New Model of Major Power Relations?
Wilson Center
3:30 – 5:00PM

On December 4 and 5, the Kissinger Institute and the China Institute for International Studies will hold a groundbreaking dialog on U.S.-China relations. In an effort to build relationships between, and gain the insights of, promising young leaders from both countries, the Kissinger Institute and the China Institute for International Studies are bringing together 16 fully bilingual experts from a variety of fields for an unconstrained and uninterpreted dialog on major issues in Sino-U.S. relations. The U.S.-China Young Leaders Dialogue is developing a platform for new voices and constituencies in U.S.-China relations, with an eye toward finding new approaches to joint challenges. At this public session of the off-the-record Dialogue, four conference participants will offer their views on prospects for a new model of major power relations.

(image courtesy of Dell)

Delving Deeper: Living in the Post-Antibiotic Era

by Siddha Hover, posted in News, Policy Review, Research Notes

By Yong-Bee Lim

The Post-Antibiotic Era Problem: What are the Issues, and How Can Adaptive Clinical Trials Potentially Help?

Nostalgia is a powerful thing. When people get nostalgic, they are cognitively living in the past; in this constructed past, the past seems rosy, and often conceived of as more positive than the present. That said, even with rose-tinted glasses, it is hard to argue that life (if defined as survivability) was better before the introduction of antibiotics. For example, mortality rates from pneumococcal pneumonia were 30-35% in the pre-antibiotic era, with the therapy often being quarantining patients.[1] Antibiotics have allowed for both the morbidity and mortality rates of pneumococcal pneumonia to drop to nearly zero in developed countries.[2] Furthermore, antibiotics allow procedures that would have been impossible in a pre-antibiotic era; organ transplants, invasive procedures, and intensive care units would not be possible without effective antibiotics.

A recent piece of news to hit the public health radar involves a man in New Zealand named Henry Pool. Pool, while teaching English in Vietnam, was operated on following a brain hemorrhage. When flown following the operation to a Wellington hospital, it was discovered that he carried a bacteria strain identified as KPC-Oxa 48: a strain of bacteria that is resistant to every antibiotic currently available to man. To contain the possibility of the strain of bacteria getting out, Pool was forcibly quarantined for 6 months until he passed away. [3]

This recent death in New Zealand highlights a threat that looms ever closer in the public health horizon: the post-antibiotic era. Due to a number of factors, including over-prescription of antibiotics to patients and over-use of antibiotics in farming and animal cultivation, bacteria have undergone evolutionary pressures to resist and overcome the mechanisms of our current arsenal antibiotics; several adaptations include the production of enzymes to modify antibiotics, cell wall changes that prevent the ingress of antibiotics inside the bacterium, and the creation of pumps to transfer antibiotics outside of the cell before the antibiotic’s effects are actualized. Furthermore, evidence points to the fact that multiply-resistant bacteria are not staying confined to hospitals as they traditionally have; certain bacteria such as Streptococcus pneumonia and Staphylococcus aureus with partial/complete resistance to penicillin have been detected in community populations.[4]

The concept of antibiotic resistance is not a foreign one to scientists and individuals in the public health sector. Staphylococcus aureus was actually noted to have started developing antibiotic resistance to penicillin as early as the 1940s.[5] Despite this knowledge that antibiotic resistance could, and would, develop over time, very little is available in regards to innovative new antibiotics to counter the rising threat of antibiotic-resistant bacteria. There has been “no major classes of antibiotics introduced” between the years of 1962 and 2000;[6] furthermore, while representatives of novel antibacterial classes (linezolid: 2000, daptomycin: 2003, retapamulin: 2007) have been registered, the chemical classes from whence these representatives originate were patented or reported historically (oxazolidnones: 1978, acid lipopetides: 1987, pleuromutilins: 1952).[7]

If the threat is realized, then, why is there such paucity in the development and production of novel and effective antibacterial therapies? Part of the equation has to do with the society we live in; money is important to companies.  Over the past several decades, a number of large pharmaceutical companies have drastically cut funding and maintaining the internal capacity for R&D of antibacterial therapies. It is often argued that this decline is partially explained by the fact that pharmaceutical companies seek to shift R&D resources from antibacterial drug discovery programs to other, more profitable therapy areas such as musculoskeletal and central nervous system (CNS) drugs.[8],[9] The net effect of various economic barriers involved in the development of an antibiotic (if successful) is a net loss of $50 million dollars compared to a $1 billion gain for a new musculoskeletal drug at the time of discovery.[10] In addition, mergers and take-overs of pharmaceutical companies often result in a restructuring of priorities and personnel; these restructures have often included the loss of research groups with expertise in antibiotic drug discovery.[11]

So if part of the issue is economics, what can be done to better galvanize and incentivize pharmaceutical companies to come back and do R&D on antibacterial drugs? One area where companies often hemorrhage money is in the clinical trials necessary to prove both the safety and efficacy of a product. Oftentimes, the bulk of R&D funds are spent on clinical trials. Clinical trials (depending on the size of the sample needed to test the product, the cost of developing the product itself, and other factors) can run in the ballpark of $100 million dollars per trial; with a minimum of 3 phases of clinical trials (with a high probability of repeating at least one phase of a trial), it is easy to see a successful product would cost a minimum of $400 million dollars in clinical trials alone.[12]

Under the current model of clinical trials, trials are clearly demarcated between phases (Clinical Phase 1, Clinical Phase 2, and Clinical Phase 3) that must be done in a sequential fashion. Furthermore, these trials are rigid in the fact that parameters may not be changed during the course of a trial; all participants must be kept throughout the trial, dosages may not be altered, and trials (except under certain circumstances) must be completed until the end. Among a number of situations, this lock-step approach inflates costs when observations might indicate:

–          A certain subset is not responding to a dose (perhaps the dose is too low)

–          The entire sample is not responding to the product (at any dose)

Using innovative, high-level Bayesian biostatistics, a new avenue of clinical research design is being explored that may help alleviate some of the costs of clinical trials. Adaptive clinical trials are specifically designed studies that are meant to “adapt” as a clinical trial proceeds; these adaptations occur through an analysis of the accumulated results in a trial.[13] As opposed to the lock-step and rigid clinical trial structure that is currently used, adaptive clinical trials allow modifications to be introduced during the trial phase. These modifications could include, but are not limited to:

–          Sample size re-estimation: If the number of people for a trial is too small or too large, this can be adapted during the trial.

–          Early stopping of clinical trials: In the event that there is evidence that the product isn’t performing the way it is supposed to (lack of efficacy), trials can be shut down to save funds and resources.

–          Dropping suboptimal groups: In the event that there is evidence that the product isn’t effective in a subgroup of the trial sample (perhaps a group with a low dose is not presenting results), then the group could be dropped to save funds and resources.

–          Overlapping trials: Adaptive trials could overlap phases (the tail end of phase 1, for example, could overlap the beginning of phase 2), resulting in faster clinical trial completion and, hopefully, swifter licensure.

It should be noted that this type of approach is very new, and is only just garnering use in various areas that require clinical trials. For example, it has not been used, as of this post, for the development of Medical Countermeasures (MCMs). However, if it can be successfully executed, it holds possibilities in significantly cutting down both the temporal constraints, as well as the financial burdens, of attaining the novel and effective antibiotics that are necessary to help curb the growing antibiotic-resistant bacteria threat.

Perhaps the phraseology “post-antibiotic era” is too strong; it seems to evoke a sense of fear, and fails to address the idea that future innovations exist in the pipeline to potentially deal with issues of current levels of antibiotic resistance. However, what can be said is that we are starting to run out of options in our bag of tricks, and it will take more than a wave of a wand and an “abracadabra” to resolve this threat to the status quo: a public health era in which antibiotics work against bacteria to increase survivability. While there are multi-faceted issues contributing to this issue, the ability to help make antibacterial R&D more financially viable for pharmaceutical companies (through the use of innovations such as adaptive clinical trials) could help in dealing with this public health concern.
______________________________

Yong-Bee Lim is a PhD student in Biodefense at George Mason University. He holds a B.S. in Psychology and an M.S. in Biodefense from George Mason University as well. Contact him at ylim3@masonlive.gmu.edu or on Twitter @yblim3.

[1] Shai Ashkenazi. (2012). “Beginning and possibly the end of the antibiotic era,” Journal of Pediatrics and Child Health, 49 (3): pp. 179 – 182.

[2] RP Wenzel and MB Edmond. (2000). “Managing antibiotic resistance,” New England Journal of Medicine, 343: pp. 1961 – 1963

[3] “Kiwi dies with bug no drug could beat,” New Zealand Herald, accessed 11/23/2013: http://m.nzherald.co.nz/nz/news/article.cfm?c_id=1&objectid=11159413

[4] LF Chen, T Chopra, and KS Kaye. (2009). “Pathogens resistant to antimicrobial agents,” Infectious Disease Clinics of North America, 23: pp. 817 – 845

[5] “Methicillin-Resistant Staphylococcus aureus (MRSA),” National Institute of Allergy and Infectious Diseases, accessed 11/26/2013, http://www.niaid.nih.gov/topics/antimicrobialresistance/examples/mrsa/pages/history.aspx

[6] MA Fischbach and CT Walsh. (2009). “Antibiotics for emerging pathogens,” Science, 325: pp. 1089 – 1093

[7] Lynn L. Silver. (2011). “Challenges of antibacterial discovery,” Clinical Microbiology Reviews, 24 (1): pp.71 – 109

[8] S. Projan. (2003). “Why is big pharma getting out of antibacterial drug discovery?” Current Opinion in Microbiology, 6 (5): pp. 427 – 430

[9] R Finch and P Hunger. (2006). “Antibiotic resistance – action to promote new technologies,” Journal of Antimicrobial Chemotherapy, 58 (Suppl): pp. 3 – 22

[10] Priya Sharma and Adrian Towse. (2011). “New drugs to tackle antimicrobial resistance: Analysis of EU policy options.”

[11] I. Chopra. (2008). “Treatment of health-care-associated infections caused by Gram-negative bacteria: a consensus statement,” Lancet Infectious Diseases, 8: pp. 133 – 139

[12] “How the FDA Stifles New Cures, Part I: The Rising Cost of Clinical Trials,” Forbes, accessed 11/26/2013, http://www.forbes.com/sites/aroy/2012/04/24/how-the-fda-stifles-new-cures-part-i-the-rising-cost-of-clinical-trials/

[13] Donald A. Berry. (2010). “Adapative clinical trials: The promise and the caution,” American Society of Clinical Oncology, 29 (6): pp. 606 – 609

The Pandora Report 11.29.13

by Siddha Hover, posted in Pandora Report

Highlights include a new Q-fever vaccine, MERS in Qatari camels, revised 2009 H1N1 deaths, black silicon the bacteria slayer, and the new, FDA-approved, H5N1 vaccine. Happy Friday!

Eyeing Terrorist Potential, Pentagon Seeks Vaccine Against Cold War-Era Bioweapon

The Pentagon is pushing forward with plans to develop a vaccine against Q-fever, the disease caused by the bacterial agent Coxiella burnetii. While the majority of Q-fever cases are asymptomatic, C.burnetti is a spore former, and is therefore both hardy and stable. However, as the primary reservoirs of the disease are sheep, goats and cattle, the disease tends to be confined within slaughterhouse workers. The acute form of the disease has a fatality rate of less than one percent, while the chronic form ranges from five to 25%.

National Journal – “The United States investigated the agent’s warfare potential and the Soviet Union fully weaponized it decades ago, long before both countries formally denounced biological arms in the 1970s. The disease also occurs in nature and has affected hundreds of U.S. troops deployed overseas. It can produce fever, pneumonia, and numerous other symptoms associated with a variety of pathogens. Certain antibiotics are considered effective against the bacteria, but no vaccine is presently sold in the United States, according to the Federation of American Scientists. An existing vaccination available abroad reportedly can cause side effects such as abscesses and swollen joints.”

MERS virus found in camels in Qatar, linked to human spread

The Middle Eastern Respiratory virus has been detected in three Qatari camels, according to an unpublished study. While the press release does not detail whether live virus or antibodies to the virus were detected, there have been two confirmed cases of human infection related to the barn housing the infected camels. Although camels and bats are the leading candidates for potential reservoirs of the virus, there still exists too little conclusive evidence supporting either.

Reuters – “British researchers who conducted some of the very first genetic analyses on MERS last September said the virus, which is from the same family as Severe Acute Respiratory Syndrome, or SARS, was also related to a virus found in bats…Ab Osterhaus, a professor of virology at the Erasmus Medical Centre in The Netherlands that worked on the camel study, told Reuters the results were confirmed by a range of tests including sequencing and antibody testing. Dutch scientists said in August they had found strong evidence that the MERS virus is widespread among one-humped dromedary camels in the Middle East – suggesting people who become infected may be catching it from camels used for meat, milk, transport and racing.”

W.H.O. Estimate of Swine Flu Deaths in 2009 Rises Sharply

The WHO has significantly revised its fatality estimates for the 2009 outbreak of H1N1, which are estimated be ten times too low. It’s original numbers were just over 18,000 – according to a study published this week, the number of fatalities from the virus alone was actually closer to 203,000. When fatalities resulting from secondary conditions because of the virus are counted, the number approaches 400,000. There are a couple of  important reasons for revising fatality counts, the first of which is it remedies accusations of sensationalizing the potential threat to sell vaccines.

New York Times  – “The estimated death toll closely matches that of a study published in June 2012 by the Centers for Disease Control and Prevention. That study, based on early data, estimated that 201,000 people died of flu and respiratory causes and another 83,000 died of related cardiac problems. Both counts were many more than the 18,449 laboratory-confirmed cases that the W.H.O. stood by as its official count in 2009 because agency officials were reluctant to guess at fatality rates. Some politicians, particularly in Europe, used the low official W.H.O. death rate to argue that fear of the pandemic had been overblown. They accused vaccine companies of fanning the public’s fears to sell more of their product.”

Bactericidal activity of black silicon

From dragonfly’s wings to black silicon? In a recent study originating from Australia, scientists discovered that dragonfly wings were absolute shredders of bacteria. The structure of the wings destroys bacterial cell walls of both gram positive and gram negative bacteria upon contact. Now, shown that black silicon has similar bactericidal properties as well. While black silicon is not readily mass produced, there are several substances with similar nano features which can be. Our first thoughts here are hospitals and doorknobs.

Nature – “Both surfaces are highly bactericidal against all tested Gram-negative and Gram-positive bacteria, and endospores, and exhibit estimated average killing rates of up to ~450,000 cells min−1 cm−2. This represents the first reported physical bactericidal activity of black silicon or indeed for any hydrophilic surface. This biomimetic analogue represents an excellent prospect for the development of a new generation of mechano-responsive, antibacterial nanomaterials.”

FDA approves H5N1 bird flu vaccine

The FDA has approved the first adjuvanted H5N1 vaccine, designed primarily for those who have frequent interactions with poultry. As the vaccine is adjuvanted, less antigen is required to stimulate an immune response. The vaccine, which is administered in two doses three weeks apart, is designed to support existing vaccine supplies in the national stockpile.

Disaster News – “The vaccine, manufactured by GlaxoSmithKline, was developed in partnership with the Biomedical Advanced Research and Development Authority, which is under the Office of the Assistant Secretary for Preparedness and Response of the U.S. Department of Health and Human Services.’This vaccine could be used in the event that the H5N1 avian influenza develops the capability to spread efficiently from human to human, resulting in the rapid spread of disease across the glove.’ Dr. Karen Midthun, director of the FDA’s Center for Biologics Evaluation and Research, said in the news release. Among people who have become infected with H5N1, mortality is about 60%, according to WHO. Health officials have determined the H5N1 strain of influenza has ‘pandemic potential’ because it continues to affect wild birds and poultry populations, and most humans have no immunity to it.”

(image: Bahman Farzad/Flickr)

Image of the week: Salmonella!

by Siddha Hover, posted in Images

In honor of Thanksgiving and our slightly perverse senses of humor, this week’s image is of everyone’e least favorite holiday bacteria – Salmonella! Pictured below is Salmonella typhimurium, the causative agent behind your run of the mill gastroenteritis.  In order to avoid encountering this particularly unfortunate pathogen, we recommend you check out the CDC’s guidelines for a pathogen-free Thanksgiving. Which, incidentally, is what we wish you all!

SALMON_1

Pictured in this lovely SEM, we have Salmonella typhimurium in red, invading human cells.

(image credit: Rocky Mountain Laboratories, NIAID, NIH)

 

WHO: MERS update

by Siddha Hover, posted in News

The World Health Organization released an update on MERS cases today. According to this most recent report, a further three cases of MERS have been detected in Saudi Arabia in the last week. Of the three patients, aged 73, 65, and 37 respectively, two had underlying medical conditions, and two have subsequently died, each within two weeks of becoming symptomatic. None of the three cases had prior, documented exposure to animals.

These most recent cases bring the global count up to 160 laboratory-confirmed cases, with 68 deaths.

For the full update, visit the WHO website here.