Tag: anti-microbials

Pandora Report 3.24.2017

by spopescu, posted in Pandora Report

Welcome to the start of the weekend and World TB Day! The WHO estimates that just in 2015, 1/3 of people with TB missed out on quality care and 480,000 people developed multidrug-resistant TB.

Public Health Concerns in Trump’s New Budget
President Trump’s newly released proposed budget blueprint makes drastic cuts to many programs, of which, one of the hardest hit is HHS. On top of the cuts to science and public health, there is something buried within the budget that is concerning ex-CDC director, Dr. Tom Frieden. Frieden worries about the proposal to award block grants to states, which would allow them to decide how to respond to public health issues (think Ebola, Zika, etc.). “That proposal is ‘a really bad idea,’ according to Dr. Tom Frieden, who until this past January was director of the U.S. Centers for Disease Control and Prevention. Currently, the CDC experts work with state and local governments to devise evidence-based plans to respond to public health issues, such as foodborne and infectious disease outbreaks. With a block grant, states can use the federal money to replace their own spending in certain areas or spend the money unwisely, ‘and never have to report what they have done or be held accountable for it,’ Frieden said.” A withdrawal of one fifth of NIH’s budget would mean a deep slash to biomedical and science research funding.  These cuts will also impact foreign aid, which has many worried about the role of public health interventions in foreign countries. Bill Gates recently talked to TIME magazine regarding the safety implications of cutting foreign aid. “I understand why some Americans watch their tax dollars going overseas and wonder why we’re not spending them at home. Here’s my answer: These projects keep Americans safe. And by promoting health, security and economic opportunity, they stabilize vulnerable parts of the world.” Gates points to the role of overseas public health work like polio eradication, Ebola outbreak response, and America’s global HIV/AIDS effort (PEPFAR), which points to the stabilizing role that strengthening public health can have in a country.

Summer Workshop on Pandemics, Bioterrorism, and Global Health Security
From Anthrax to Zika, we’ve got the place to be in July for all things biodefense. This three-day workshop will provide you with not only seminars from experts in the field, but also discussions with others interested in biodefense. You can check out the flyer and register for the event here. The best part is that we’re doing an early-bird registration discount of 10% if you sign up before May 1st. A returning participant, GMU student/alumni, or have a group of three or more? You’re eligible for an additional discount! Check out the website to get the scoop on all our expert instructors and the range of topics the workshop will be covering.

Unseen Enemy Documentary 
Mark your calendars for this upcoming infectious documentary on the lurking pandemics that worry experts. Airing on April 7th, Unseen Enemy will follow researchers looking for the early warning signs of diseases that could cause the next pandemic. The National Academy of Medicine will be hosting a special D.C. premiere of the film on April 2nd, that you can even attend.

Expert Views on Biological Threat Characterization for the U.S. Government: A Delphi Study 
Biological threat characterization (BTC) is mixed bag of risk and reward. The laboratory research involving deadly pathogens as a means for biodefense can translate to better risk assessments but also the potential for biosafety failures. To better address this issue, researchers performed a Delphi study to gather opinions from experts around the country. “Delphi participants were asked to give their opinions about the need for BTC research by the U.S. government (USG); risks of conducting this research; rules or guidelines that should be in place to ensure that the work is safe and accurate; components of an effective review and prioritization process; rules for when characterization of a pathogen can be discontinued; and recommendations about who in the USG should be responsible for BTC prioritization decisions.” Following their assessment, the researchers found that experts agree that BTC research is necessary, but there is also a need for continued oversight and review of the research to reduce as much risk as possible. “It also demonstrates the need for further discussion of what would constitute a ‘red line’ for biothreat characterization research—research that should not be performed for safety, ethical, or practical reasons—and guidelines for when there is sufficient research in a given topic area so that the research can be considered completed.”

GMU Schar School PhD Info Session
If you love global health security and have been wanting to further your education, come check out our PhD info session next Wednesday, March 29th at 7pm in Arlington. You can come learn about our biodefense PhD program from the director, Dr. Koblentz, and hear from several students about their experiences. The info session is a great way to find out what a GMU Schar PhD entails, the application process, and what current students think!

What Biosecurity and Cybersecurity Research Have In Common
Kendall Hoyt is looking at the similarities between these two research fields and how work into the unknown can often expose and create vulnerabilities. Did I mention Kendall is one of the instructors at our biodefense Summer Workshop? Hoyt provides two examples to really hone in on this point – to defend against a dangerous pathogen, we have to isolate and grow it to try and develop treatment or a vaccine and to defend against a cyberattack, we need to know how to break into the computer system. That whole dual-use dilemma creates a lot of risk-versus-reward scenarios for biosecurity and cybersecurity researchers. While the research is highly relevant and necessary, government efforts to control or maintain oversight have been challenging. Do we pull back the reigns on innovation or run the risk of a security breach or a big “whoops” moment? “Intellectual property and cybersecurity legislation—namely the Digital Millennium Copyright Act and the Computer Fraud and Abuse Act—has similarly stifled legitimate scientific and commercial activities and delayed defensive applications. In one well-known example, fear of prosecution under DMCA deterred a Princeton graduate student from reporting a problem that he discovered: Unbeknownst to users, Sony BMG music CDs were installing spyware on their laptops.” Hoyt also points out the biosecurity efforts that have begun looking not just at the pathogens and publications, but the laboratory techniques that are used for such research. Certain experiments (like gain of function work) have the capacity to increase transmissibility or host range. “For all of their similarities, key differences between biosecurity and cybersecurity risks and timelines will dictate varied regulatory strategies. For example, zero-day exploits—that is, holes in a system unknown to the software creator—can be patched in a matter of months, whereas new drugs and vaccines can take decades to develop. Digital vulnerabilities have a shorter half-life than biological threats. Measures to promote disclosures and crowd-sourced problem-solving will therefore have a larger immediate impact on cybersecurity. Still, both fields face the same basic problem: There are no true ‘choke points’ in either field. The U.S. government is not the only source of research funds and, thanks in large part to the internet itself, it is increasingly difficult to restrict sensitive information.” In the end, Hoyt notes that both fields and their regulations will need to relax the governance process and be a bit more flexible and mobile with how they control items. Both fields are constantly evolving, which means regulators need to be just as fluid.

How To Prepare For A Pandemic
NPR decided to create a “Pandemic Preparedness Kit” based off the continuous questions related to the ongoing news of increasing infectious disease threats but little info in terms of practical things people can do. While these aren’t things you can go out and buy for your home, the list hits close to home in terms of things we should be focusing our efforts and funding on. Firstly, vaccines. This is a no brainer and yet, we’ve become the habitual users of the theme “create it when we’re struggling to contain an outbreak”. Secondly, virus knowledge. “One of your best weapons during a disease outbreak is knowledge, says Dr. Jonathan Temte of the University of Wisconsin. ‘Keep up with the news and try to understand what threats might be out there,’ he says. For example, new types of influenza are one of the biggest threats right now — in terms of pandemic potential, Temte says. But if you know how to protect yourself from one type of influenza, you can protect yourself from all of them.” Lastly, and my personal favorite, is very clean hands. While every disease is different, one of the most basic and fundamental truths for infection prevention and control is hand hygiene. These three are solid ways to better prepare for future outbreaks, pandemics, emerging infectious diseases, and just about anything infectious that makes you a bit worried.

CARB-X Mission– When I first read the name of this group, I thought it was some kind of fitness fuel, but I was pleasantly surprised to see this initiative is working to fight antibiotic resistance. CARB-X is a collaboration between NIAID and BARDA to help accelerate the development of antibacterials over the next 25 years. The goal is to help combat antimicrobial resistance through a diverse portfolio and partnership. Make sure not to miss their March 30th meeting from 11am-noon on antibiotic resistance. “CARB-X (Combating Antibiotic Resistant Bacteria Accelerator) was launched in August 2016 to accelerate pre-clinical product development in the area of antibiotic-resistant infections, one of the world’s greatest health threats. CARB-X was established by BARDA and NIAID of the U.S. Department of Health and Human Services along with Wellcome Trust, a global charitable foundation dedicated to improving health. This partnership has committed $450 million in new funds over the next five years to increase the number of antibacterial products in the drug-development pipeline.” While CARB-X may not be the latest workout supplement, it’s definitely a boost to performance in the fight against antimicrobial resistance.

New Roles and Missions Commission on DHS Is Urgently Needed
GMU biodefense PhD alum, Daniel Gerstein, is looking at DHS and pointing to the need for a Roles and Missions Commission. It’s been almost 15 years since DHS was created under rapid and urgent circumstances, which means that it’s time to look introspectively. “More generally, a roles and missions review could also examine whether the department is properly resourced for all its missions. For example, a joint requirement council was recently established for the department composed of less than 10 government civilians. Is this adequate for supporting requirements development activities for a department of over 240,000 personnel?” Gerstein looks at some of the big issues that require a comprehensive review, like centralization versus decentralization, management of R&D and engineering, and critical infrastructure issues related to national security and safety. Another component needing review is the human factors issue that impacts homeland security. How are the relationships between departments, with state and local authorities, or with the public? “The effort should not necessarily be viewed as a requirement for change, but rather an opportunity to reexamine DHS and its relations with the rest of government, the nation and its citizens, and even with our international partners across the globe. Finally, a homeland security roles and mission commission would be an ideal lead-in to a much needed update to the original 2002 authorizing legislation.”

Deadliest Enemy: Our War Against Killer Germs
Don’t miss this event on Thursday, March 30th, hosted by New America with speakers Michael T. Osterholm and Mark Olshaker. “In today’s world, it is easier than ever for people and material to move around the planet, but at the same time it is easier than ever for diseases to move as well. Outbreaks of Ebola, MERS, yellow fever, and Zika have laid bare the world’s unpreparedness to deal with the threat from infectious diseases. In Deadliest Enemy: Our War Against Killer Germs Dr. Michael Osterholm and Mark Olshaker marshal the latest medical science, case studies, and policy research to examine this critical challenge.”

Stories You May Have Missed:

  • The Feds Are Spending Millions to Help You Survive Nuclear War – North Korea’s recent firing of four ballistic missiles from Pyongyang into the ocean off Japan’s coast has brought back worries of nuclear attacks. While the days of stocking a bomb shelter are in the past, the U.S. government isn’t slowing down efforts to protect Americans. “Over the last ten years the US has poured millions of dollars into technologies and treatments it hopes to never have to use, but could, in the event of a nuclear catastrophe. From assays that measure radiation exposure to cell therapies that restore dwindling blood cells to liquid spray skin grafts, government officials are now far better equipped to deal with diagnosing and treating people if the unthinkable were to happen. And the next generation of treatments are being funded right now.” DHHS projects like BARDA and Project BioShield are just some of the sources for ongoing research to strengthen protection, whether it be a nuclear blast or reactor melt-down.
  • Disinfection and the Rise of the Superbug – GMU biodefense PhD student Saskia Popescu is addressing the growing disinfection needs as we teeter on the edge of the antibiotic abyss. Disinfection is already a challenge in healthcare however, the rise of more resistant germs means that efforts often need to be ramped up. The recent influx of Candida auris infections that we talked about last week really brings this issue to point in that this emerging infection is difficult to get rid of via traditional disinfection routes. “As new organisms are identified and existing ones become resistant to antimicrobials, the availability of strong disinfecting products has become even more pivotal.”
  • China and EU Cut Brazilian Meat Imports Amid Scandal– If you’re a fan of importing Brazilian meat, you may have to hold off for a while. A recent police anti-corruption probe is accusing inspectors of taking bribes to allow the sale of rotten and salmonella-contaminated meats from the largest exporter of beef and poultry. As the news unfolds, the Brazilian government is criticizing gate police as alarmist. “As the scandal deepened, Brazil’s Agriculture Minister Blairo Maggi said the government had suspended exports from 21 meat processing units.”
  • Study on Interferon for Treatment of Ebola Infection – The common hepatitis treatment is now being tested out on Ebola patients to help alleviate their symptoms. The pilot study was performed from March-June of 2015 and  had some interesting results. “When compared to patients who received supportive treatment only, 67 per cent of the interferon-treated patients were still alive at 21 days in contrast to 19 per cent of the former patients. Additionally, the viral blood clearance was faster in those patients treated with Interferon ß-1a. Many clinical symptoms such as abdominal pain, vomiting, nausea and diarrhea were also relieved earlier in the interferon-treated patients. A further 17 patients in other Guinean treatment centres who matched the interferon-treated patients based on age and the amount of Ebola virus in their blood were included in the analysis. These added patients, who did not receive interferon, more than doubled their risk of dying as a result of not being treated with the drug.”

Pandora Report 3.10.2017

by spopescu, posted in Pandora Report

Looking for a great podcast on CRISPR? Check out RadioLab – they also have a captivating one on patient zeroes throughout history!

Summer Workshop on Pandemics, Bioterrorism, and Global Health Security: From Anthrax to Zika 
If you’re looking to learn more about global health security, synethic biology, biosecurity, and what exactly “biodefense” entails, you’ll want to mark your calendar for the GMU Biodefense three-day, non-credit summer workshop on July 17-19, 2017! Participants will look at the challenges facing the world at the intersection of national security, public health, and the life sciences. Instructors for the workshop range from FBI special agents to biodefense professors and USAMRIID commanders. The workshop will look at the spectrum of biological threats – including naturally occurring disease outbreaks such as SARS, Zika, and Ebola, lapses in biosafety, dual-use research of concern, and the threat of bioterrorism. From now until May 1st, you can take advantage of the early bird registration discount!

Glaring Gaps: America Needs A Biodefense Upgrade
GMU biodefense PhD alum Daniel M. Gerstein is emphasizing the need to strengthen American biodefense capabilities. “Recent legislation has called for a comprehensive biodefense strategy. If carried out in a thorough and systematic way, and properly funded, this will be a great improvement for the country and the world.” Gerstein notes that while the National Defense Authorization Act for Fiscal Year 2017 called for a joint biodefense effort, there is still a desperate need for a structured and systematic approach. Perhaps one of the biggest issues Gerstein found is the current view of biodefense as a series of programs. Approaching global health security threat requires us to view biodefense as a complex system, not a series of programs. To fix the glaring gaps in U.S. biodefense efforts, he notes that any remedy will have to accept the complexity of the problem and that there is no single panacea. Internal coordination, improvement of diagnostics and treatment, and technology management are all things that must be addressed to strengthen American biodefense. “Export controls in the United States, for example, actually hinder international collaboration. Exchanging pathogen strains used in the development of medical countermeasures, diagnostics, and bio-surveillance remains difficult – even, at times, for close international partners. In one case, the United States was attempting to share a strain of the Ebola-Reston pathogen with the government of Australia, but export laws prevented this sharing, so the strain was instead acquired from the Philippines, where the strain originated.” While we’ve made great strides since the Amerithrax attacks, there is much to be done to create a systematic and resilient biodefense strategy.

Chemical Weapons Reportedly Used in Mosul
The WHO has recently activated an emergency response plan with several partners to help treat twelve people for potential exposure to chemical weapons in Iraq. “Lise Grande, the UN humanitarian coordinator in Iraq, called for an investigation. ‘This is horrible. If the alleged use of chemical weapons is confirmed, this is a serious violation of international humanitarian law and a war crime, regardless of who the targets or the victims of the attacks are,’ she said in a statement.” Many are pointing to ISIL as the likely culprit since they hold the majority of west Mosul and have a history of rudimentary use of chemical weapons.

China’s Growing Bird Flu Worries  
Despite a recent surge in human A(H7N9) cases, the WHO has stated that the risk of an epidemic remains low. Even with this release, the development of two distinct strains in a disease that has a mortality rate hovering around 30%, has many worried. “That will probably force development of a second small stockpile of emergency vaccine to be rolled out if the virus becomes more transmissible and threatens to turn into a pandemic, a scientist at the Centers for Disease Control and Prevention said. Flu specialists from around the world gathered in Geneva this week to assess the global influenza situation and discuss with vaccine companies which viral strains should be in next winter’s flu shots. China has had 460 lab-confirmed human cases of H7N9 bird flu this winter, said Dr. Wenqing Zhang, head of the W.H.O.’s global influenza program. That is the most in any flu season since the first human case was found in 2013.” Interestingly, around 7% of the new H7N9 cases were resistant to drugs like Tamiflu, which has many researchers working to make a H7N9 seed vaccine, including a secondary one due to the split strains. Coming on the heels of this outbreak, US officials have announced that highly pathogenic avian influenza (HPAI) was found in a commercial poultry farm in Tennessee. 700 birds died from infection and almost 73,000 were destroyed. The farm is a contracted supplier of chicken meat for the U.S.’s biggest supplier, Tyson, which released an announcement on March 5th regarding testing of local birds, etc.

Global Health Security Index Development
Johns Hopkins Center for Health Security recently received a grant from the Open Philanthropy Project and the Robertson Foundation to coordinate with the Nuclear Threat Initiative (NTI) and the Economist Intelligence Unit (EIU) to develop a Global Health Security Index. “The mission of the index is to encourage progress towards a world that is capable of preventing epidemics of international impact (either natural, accidental or deliberate) from arising, or, should, prevention fail, respond quickly to contain them.” The first phase of the project will aim at developing framework that can measure a country’s level of health security. While the GHSA and JEE are processes to increase transparency, preparedness, and country capabilities, the goal of this index is to fill the gaps in motivation and also the factors that are not in the hands of the health sector.

Antimicrobial Resistance in Pets: Are We Ignoring A Looming Threat? 
GMU biodefense PhD student Saskia Popescu is looking at the threat of antibiotic resistance, but from a somewhat forgotten patient population – our pets. The recent WHO list of worrisome antimicrobial resistant bugs has drawn a lot of attention to the growing threat of an antibiotic apocalypse however, sometimes it takes a personal experience to look outside the box. Pulling from experiences of dealing with drug resistance in her dog to the loss of SeaWorld’s controversial orca, Tilikum, Popescu notes the rising threat of AMR brewing in domesticated animals. Sadly, it seems that many veterinarians and infectious diseases researchers have been drawing attention to the role of household animals in antimicrobial resistance and yet, just like the human issue, it’s not getting the attention it deserves. In her article, Popescu points to the need to start addressing the full circle of microbial resistance, starting with our furry friends.

Stories You May Have Missed:

  • Constraining Norms for Cyber Warfare Are Unlikely – GMU Biodefense PhD alum, Brian M. Mazanec, is talking to the Georgetown Journal of International Affairs about the realities of norms for cyber warfare. The question of whether constraining international norms for cyber warfare will emerge and thrive is of paramount importance to the unfolding age of cyber conflict. Some scholars think that great powers will inevitably cooperate and establish rules, norms, and standards for cyberspace. While it is true that increased competition may create incentives for cooperation on constraining norms, Mazanec argues that norm evolution theory for emerging-technology weapons leads one to conclude that constraining norms for cyber warfare will face many challenges and may never successfully emerge.
  • ABSA International Webinar- Behaving Safely in the Laboratory: Understanding Complexities of Building and Sustaining a Culture of Safety–  ABSA is hosting a 2-hour webinar session for three days. “The webinar will be offered Monday, April 3; Wednesday, April 5 and Friday, April 7, 2017.  Millions of dollars on engineering.  Thousands of dollars on PPE.  Hundreds of hours spent writing SOPs – and in one instant all of these controls can be negated with one inappropriate behavior.  Behavior is the bridge between written plans and desired outcomes.  But what does it take to behave safely?  Day 1 will focus on what it takes for an individual to behave safely – as behavior requires five critical items – and without these items – sustained behavior cannot occur. Day 2 will focus on motivating behavior – the differences between leadership and management – and the motivating factors which are extrinsic, systemic, and intrinsic. Day 3 will focus on building and sustaining a ONE SAFE culture – blending the efforts of the workforce, leadership, and safety officials.”
  • High Flu Activity Throughout the U.S. – The CDC has warned that the U.S. is still experiencing high flu activity in all regions. This flu season has seen elevated pediatric mortality, with six reported last week, bringing the total to forty pediatric deaths. “The CDC said there have been more hospitalizations and clinical visits for influenza-like illness (ILI) at this point in the flu season than in 2012-13, another season when H3N2 strain predominated. The CDC said the cumulative overall rate is 39.4 hospitalizations per 100,000 people. During the 2012-13 flu season, the rate was (38.2 per 100,000).”

 

Synthetic bio and dual-use anti-microbials

by Siddha Hover, posted in News

By Daniel McGown

Two articles were published in ACS Synthetic Biology this week, one from an MIT team and another from a team at Nanyang Technological University, iteratively outlining an approach for the custom design of a microbial hunter-killer against a pathogenic species.

In the first paper, Saurabh Gupta, Eran Bram, and Ron Weiss outlined proof of concept construction of an E. coli strain modified to do two novel things: 1) detect a quorum sensing signal emitted by Pseudomonas aeruginosa and 2) upon detection secrete a chimeric exotoxin designed to specifically destroy P. aeruginosa cells and nothing else. This use of passive detection to trigger an active and specific offense effectively converts the E. coli strain into a trap waiting for just P. aeruginosa – and because the toxin is secreted rather than requiring destruction of the cell, the trap can keep on trapping.

Matthew Wook Chang and company take a similar design and extend it two steps farther.   Firstly, they added a method to defeat one of P. aeruginosa’s best defenses, the biofilm.  Because P. aeruginosa biofilms include DNA into the extracellular matrix, they added a secreted DNAse to eliminate the DNA and disrupt the biofilm.  Secondly and perhaps more interestingly, the team retargeted the cell’s chemotaxis system by tying E. coli expression of a chemotaxis regulation protein to the presence of P. aeruginosa’s quorum sensing signal.  This caused the E. coli to gravitate toward P. aeruginosa and release their enzymatic arsenal where it would do the most P. aeruginosa damage.  With this latter addition, then, the waiting trap instead switched over to search and destroy.

This is a really cool idea – an appealing concept in a world that is running out of anti-microbials.  It brought to mind immediately the way the Russians used to use bacteriophages to attack bacterial infections, except these can be designed modularly to strike the right target instead of hoping nature is kind enough to deliver.  One has to wonder how easily it could be used in an infection inside a living system, but a proof of concept can’t be expected to jump that chasm – it’s cool enough that it works at all.  It will be nice, though, to see how readily the approach could actually be adapted to other pathogens and how well it will work clearing infections in vivo.

One also has to wonder, though, if the same idea couldn’t be turned in a different and less pleasant direction.  Could you use it to make a pathogen worse?  Say, could you build a pathogen that used the body’s chemokine and cytokine signals to specifically detect and defeat cells regulating immune responses with chimeric leukocidins or hemolysins or some such?  Beats me, but it feels like something of a goose and gander situation.

(image: Janice Haney Carr/CDC)
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Daniel McGown is a first year PhD student in the Biodefense program with a background in molecular microbiology.