Pandora Report 12.11.2015

If you’re in Boston and enjoying a Chipotle burrito bowl, you may want to put the fork down. As many as 80 cases of norovirus were reported in association with a Boston Chipotle. The norovirus surge occurs just months after the multi-state Chipotle-linked E. coli 026 outbreak. This week we’re discussing superbugs Star Wars style, the decline of infectious disease specialists, Ebola lab stories from the field, and much more. Fun history fact Friday: on December 7, 1941, Pearl Harbor was bombed and on December 10, 1901, the first Nobel Prizes were awarded in Stockholm, Sweden 

“Phantom Menace” Superbug?
In a lab far, far away… How could we resist a Star Wars reference to antibiotic resistance? A recent CDC MMWR reported a growing incidence of a particularly concerning antibiotic-resistant organism. Carbapenem-resistant Enterobacteriaceae (CRE) are continuing to raise concerns due to cases related to endoscopic retrograde cholangiopancreatography (ERCP) scopes. Since it’s discovery, global health experts (including the CDC) have been keeping a close eye on CRE transmission and cases. A variant of CRE, called OXA-48-type carbapenemase, was seen in Enterobacteriaceae in Turkey in 2001. 52 isolates of CRE producing OXA-48-like carbapenemases were found in 43 patients in the US from June 2010-August 2015. A study in 2012 first referenced OXA-48-like carbapenemases as the phantom menace. The concerning issue with this particular CRE strain, aside from its known-resistance, is the growing emergence in the US. The difficulty in treatment and extreme care for isolation precautions makes patient care challenging. Interestingly, for those patients who provided a travel history, the majority (66%) had traveled internationally within the year before specimen collection and 55% were actually hospitalized outside the US for at least one night. The US cases involved several clusters and were spread across 19 states. Even more worrying, the laboratory diagnosis is tricky as “most U.S. clinical laboratories that test for CRE organisms wouldn’t identify this particular type of bacteria because it’s not part of standard testing.” The increase in cases and ease of hospital transmission are just a few more reasons why antimicrobial stewardship is so vital. May the force be with you!

Ebola Surveillance & Lab Response SeminarIMG_4700
In case you missed GMU’s seminar on global health security on Monday, 12/7, here’s a recap! Speakers included Dr. Matthew Lim (Senior Policy Advisor for Global Health Security, HHS, fmr Civil-Military Liaison Officer to WHO), Jeanette Coffin (Section Manager, Biosurveillance Division, MRIGlobal), and Phil Davis (Associate Scientist with MRIGlobal). Ms. Coffin and Mr. Davis discussed the operations, supported by the Defense Threat Reduction Agency’s (DTRA) Cooperative Biological Engagement Program (CBEP). The mobile lab was launched in December 2014. With only six weeks to train, prepare staff, acquire equipment, deliver, assemble, and much more, it’s a pretty impressive feat that this team pulled off. Ms. Coffin and Mr. Davis discussed how they were able to reduce much of the travel delay and time lag for Ebola testing results. Using equipment to perform RNA extraction and PCR’s, lab technicians were working in tight quarters in Moyamba and Lakka, Sierra Leone. To date, the DTRA-CBEP mobile lab operations tested 7,242 samples for Ebola. While they discussed many of the strengths like flexibility, relationship with vendors, and self-containment, there were also several challenges. Difficulties ranged from inadequate power and internet, to road reliability, food/water safety, haggling, and security issues related to petty theft and missing supply containers. Sustainability was heavily discussed as their expected withdrawal is June 2016 and the team hopes to provide education for ongoing surveillance. Next, Dr. Matthew Lim spoke of the history and impact this outbreak had on global health security. He emphasized “how much this has overturned the paradigm we have about health and security”. Dr. Lim’s discussion was fascinating in that he speaks from experience at both the WHO and HHS, pointing to the role of member states and how WHO funding cutbacks impacted outbreak response. He noted that the Global Health Security Agenda heavily emphasizes partnership of it’s 50 state members, NGO’s, and within the 11 action packages. He explained that global health affairs, in many ways, join foreign policy and health policy, highlighting the need for less siloing and more partnership to help encourage capacity measures. Overall, the standing-room-only seminar touched on both the operational struggles and the overarching role of global health security in both the Ebola outbreak, but also future preparedness efforts.

Daesh and Chem/Bioweapons?
The UK and France have moved to call ISIS, “Daesh”, to remove the association with Islam. Given Daesh’s use of mustard gas, is bioterrorism a stretch? Sandra Maksimovic-Sara of Outbreak News Today discusses their attempts to obtain biological and chemical weapons as a means of using non-conventional weapons to change their modus operandi. While she doesn’t mention tacit knowledge, Maksimovic-Sara notes that “for a biological and chemical terrorist attack, there must be some know-how and background and a professional approach, which is so far away from impatient aggressive Islamic terrorists gathered in Daesh. They want fast track acts and fast track results.” While preparedness efforts must account for a variety of attacks, it’s vital to remember technical limitations. As Dr. Sonia Ben Ouagrham-Gormley noted, tacit knowledge is a significant hurdle for non-state actors to overcome in their quest for bioweapons.

To Quarantine or Not To Quarantine? 
The fallout of the 2014 West Africa Ebola outbreak is still ongoing and while many US hospitals feel they are better prepared to handle cases, there are many that experienced negative treatment related to preparedness efforts. There have been several returned travelers from the affected countries that were put into quarantine upon arrival in their home country. While many were involved in patient care, there are several that had no interaction with patients and experienced what many would call, “fearbola“. While quarantine efforts are important for those that may have had patient interaction, risk assessments are vital. Sheri Fink of The New York Times notes that several states “have the legal authority to impose quarantines, often exceeded those guidelines, restricting the movements of returning health workers and others.” Many who were quarantined experienced public harassment, media scrutiny, and some have filed lawsuits for civil rights violations.

France’s Bioterrorism Preparedness
Given the November terrorist attacks in Paris, it’s not surprising that France is looking to ramp up their biodefense efforts. Following the arrival of a third generation vaccine, France has decided to revise its smallpox preparedness and response plans. Last revisited in 2006, the plan is to vaccinate first responders and healthcare professionals that are most likely to identify and care for smallpox cases. Smallpox has long been an organism of concern for bioweapon applications. In coordination with the Secrétariat Général de la Défense et la Security Nationale, (SGDSN- General Secretariat for Defense and National Security) these plans will include the new vaccine, Imvanex, that was developed by the Danish biotech company, Bavarian Nordic, “on behalf of the US under Bioshield”. While the new plan involves “circles” of people, the new transgenic vaccine has vastly decreased the side effects that were commonly associated with first and second generational variola vaccines. In the past, smallpox vaccines were associated with high volumes of side effects, which was a roadblock to previous mass-vaccination efforts as a biodefense strategy. France has several biopreparedness strategies that include a syndromic surveillance program, SurSaUD, a White Plan, and many other efforts to prevent, identify, and respond to health security threats. The updated French plans hope to “frustrate and deter terrorists” as well as respond to concerns of re-emerging infectious diseases. Elisande Nexon presents an overview of France’s biopreparedness efforts and the public health threats they may encounter. While the November attacks in Paris will most likely initiate additional changes to France’s biopreparedness, their existing methods are extensive and reveal national support for biodefense.

Stories You May Have Missed:

  • Infectious Disease Specialists on the Decline – The National Resident Matching Program (responsible for matching medical students with specialty training programs) announced that of the 335 infectious disease fellowship positions available, only 218 were filled. This is especially concerning as it follows several years of low matching for infectious disease positions. The Infectious Disease Society of America has even begun brainstorming recruiting tactics for what many consider a “thinking specialty” that may not have the glamor or pay that draws students into the field. Speaking from experience as an infection preventionist, the infectious disease physicians I have worked with were by far the most dedicated, intelligent, and passionate people. I think we can all safely agree that the world needs more infectious disease specialists, especially following outbreaks like those of Ebola and Zika virus.
  • USAMRIID Supported Study Traces Ebola Outbreak – a recent study lead by USAMRIID found that a majority of the Liberian Ebola cases “can be traced back to a form of the virus transmitted from Sierra Leone”. The sequencing of hundreds of isolates also supports the role of high-density neighborhoods as an accelerant for the outbreak. Interestingly, researchers found that the Ebola strain diversified in Liberia prior to being transmitted to cases in Guinea and Mali.
  • Yamuna River Harbors High Volume of Antibiotic-Resistant Organisms – Researchers found that the Yamuna river in Dehli, India, had an alarmingly high amount of resistant organisms. There were large quantities of several organisms found that showed resistance to many common antibiotics like ampicillin, streptomycin, etc.
  • MERS Was the Most 2015 Googled Word in Korea – also considered Korea’s “hottest” Twitter issue, MERS became the most searched topic after the first patient was confirmed on May 20th.

The Ebola Vaccine and the Ethics of Drug Trials

By Greg Mercer

The World Health Organization recently announced that a trial of the VSV-EBOV Ebola virus vaccine in Guinea has been “highly effective,” and that randomization in the trial would be stopped to allow for expansion of the range of subjects and protection of more people against the virus.  The trial began in March, and until recently, randomized subjects so that some received the vaccine immediately, while others received it later, after the virus’ gestation period.

A paper published in The Lancet details the study, and finds that the vaccine is highly effective and likely safe to use in the affected population.  The “recombinant, replication-competent vesicular stomatitis virus-based” vaccine is administered in a single dose via the deltoid muscle.  4,123 people received the vaccination immediately, while 3,528 people received the delayed vaccination (more on the study methodology in a moment). The researchers found that no subjects developed a case of Ebola after receiving the immediate or delayed vaccination, meaning that the vaccine proved 100% effective (with p=0.0036 at 95% CI).  These findings are excellent news for researchers, government officials, and those in the affected counties, and are fascinating from a scientific standpoint.

At The New Republic, Timothy Lahey, of Dartmouth, argues that these results, while promising, aren’t necessarily confirmed.  He notes that the lack of a placebo (because of the study’s particular methodology) makes it difficult to determine effectiveness, the vaccine could have failed to protect subjects from infection in a way that the study didn’t detect, and that a statistical aberration could mean that while the vaccine is not actually 100 % effective.  Regardless of whether these potential pitfalls affected the study or not, Lahey raises an important issue in drug testing for a disease like Ebola.  He is concerned that a lower standard for vaccines could mean that lower-income countries might not receive drugs of the same quality as rich countries, and points to past failed vaccines to illustrate the fallacy of believing that all vaccines work as intended.

The ethical dilemmas of drug testing have been front and center in the Ebola crisis.  Back in November, 2014, Nature reported on public health officials weighing the question of whether to use control groups when testing treatments for a disease with 70% mortality.  At the time, some advocated for applying experimental treatments (like the ZMapp antiviral cocktail, which had been used in patients but whose effectiveness was not entirely determined) to all patients, while others argued that these treatments might not be more effective than standard care, and that randomized trials guard against harmful side effects and provide a clearer picture of a drug’s effectiveness.

The VSV-EBOV vaccine was tested in the “ring” method that was previously used in the eradication of Smallpox.  This method eschews the double-blind placebo treatments commonly associated with drug trials.  Instead, this method creates a “ring” around new cases.  Contacts and contacts of contacts were identified by Guinea’s tracking system, and eligible adults were entered into randomization blocks, and received either the immediate or delayed vaccination.  This way, all of the subjects received the treatment, but in varying circumstances to establish effectiveness.  The full study is available via The Lancet.

Ethical drug testing is a crucial consideration, and has an imperfect past.  The National Institutes of Health’s own ethics guide cites a study that led to the United States’ ethics rules: a study that withheld syphilis treatment from 400 African-American men.  And for many, there’s good reason to be concerned about the actions of international organizations and multinational corporations.  In 1996, Pfizer conducted a study of an experimental drug on children with meningitis in Nigeria. While Pfizer maintained that the study was philanthropic, allegations arose from Nigerians and international organizations that children and parents were not informed that they were part of a study, and that Pfizer withheld treatment without consent or administered dangerous drugs.  The incident spawned a series of lawsuits and a panel of Nigerian medial experts condemned Pfizer’s actions in 2006, as reported by The Washington Post.

Epidemics and drug testing present a multitude of practical and ethical concerns, but careful consideration of the issues and sound methodology can, as they did in Guinea, produce exciting scientific and humanitarian results.

Image Credit: Psychonaught