Infection Prevention Summer Reading

With apologizes to our colleagues in the Southern Hemisphere, many of us are traveling a bit this summer and are looking for good things to read. At the top of my reading list is Ed Yong's new book, "I Contain Multitudes: The Microbes Within Us and a Grander View of Life." The book by the highly regarded UK science journalist (The Atlantic, National Geographic) digs into the relationship between microbes and animals. Unfortunately, the book won't appear until August 9th, so you'll have to be a bit patient and find something else to read.

In the meantime, I've listed five recently published journal articles/studies that will hopefully tide you over until "I Contain Multitudes" appears at your bookstore.

1) A Flawed Revision of the Common Rule (Joffe and Magnus, Annals 19 July 2016). The Common Rule is the regulatory framework that guides human subjects research, think IRB. Last September, 16 federal agencies released a Notice of Proposed Rulemaking outlining proposed changes to the Common Rule. There are several potentially important changes that could negatively impact infection prevention and stewardship studies. First, the Notice seeks to redefine all research on biospecimens, including de-identified specimens, as human subject research requiring "broad consent" before storing the specimens. The discussion didn't mentioned microbiology specimens specifically, but this requirement is concerning. Second, the Notice would only exclude QI research from review if it analyzed proven interventions and limited study endpoints to utilization outcomes (e.g. cost). However, QI projects such as quasi-experimental studies of the impact of CLABSI checklists on BSI rates or mortality WOULD require IRB review and potentially individual informed consent. (Yikes!)  My sense is this could drastically curtail important research in MDRO prevention and most infection control research. Stay tuned.

2) Control of an Outbreak of Middle East Respiratory Syndrome in a Tertiary Hospital in Korea (Park GE et al. Annals, 19 July 2016). From May to July 2015, 186 confirmed cases of MERS-CoV occurred in S. Korea. The authors provide an in-depth description of a 92-person outbreak in a single tertiary-care hospital in Seoul. Interestingly, 82 of the cases occurred after exposure to a single secondary patient cared for in their emergency department. All cases were identified through contact tracing and monitoring of exposed patients and healthcare workers and all in-hospital transmission was secondary to three patients with pneumonia and productive cough. The description of events was very sobering.

3) Colonization With Methicillin-resistant Staphylococcus aureus and Risk for Infection Among Asymptomatic Athletes: A Systematic Review and Meta-analysis (Karanika S et al, CID 15 July 2016). The results of this study suggest that you shouldn't be an athlete (6% MRSA colonization rate), especially a wrestler (22% MRSA colonization rate). Additionally, the authors reported that colonization increases the risk of subsequent skin and soft tissue infection 7 times. If only it were safer to lay around on the beach this summer.

4) Addressing Infection Prevention and Control in the First U.S. Community Hospital to Care for Patients With Ebola Virus Disease: Context for National Recommendations and Future Strategies (Cummings KJ et al. Annals 5 July 2016). Authors from the CDC, Texas Health Presbyterian Hospital in Dallas and other other institutions describe the massive infection prevention response that followed the infection of two MICU nurses who cared for the index patient from Liberia. The responses included protocols for specimen handling, managing medical waste and standardized PPE with education and monitoring. Nothing particularly novel in 2016, but the article certainly highlights the massive efforts and costs associated with the N=1 response that was required because of a chronically underfunded public health and infection prevention infrastructure.

5) A Novel Microbiome Therapeutic Increases Gut Microbial Diversity and Prevents Recurrent Clostridium difficile Infection (Khanna S et al. J Infect Dis 15 July 2016). The authors describe an alternative method to fecal transplants that could potentially avoid donor screening among other barriers. They tested SER-109, which is encapsulated spores captured from healthy human donor stool that was treated with ethanol to eliminate pathogens, for the prevention of recurrent CDI. The cohort of patients had to have had >3 CDI cases in the prior 12 months and a clinical response to antibiotic therapy for their current CDI episode immediately prior to dosing of SER-109. The 15 patients in cohort 1 received high-dose capsules (15 on day 0 and 15 on day 1) and 15 patients in cohort 2 received lower dose capsules on a single day. Overall, 87% achieved the endpoint of no CDI at 8 weeks. If you're interested in reading more, there is an excellent accompanying editorial.

Vaccine Efficacy Trials During Ongoing Epidemics: Lessons from Ebola

Investigating the efficacy of vaccines during on-going epidemics poses numerous challenges, whether the infection is Middle East Respiratory Syndrome (MERS), novel influenza strains or Ebola. Beyond the public health urgency, there are issues such as variable and unpredictable incidence and limited vaccine supplies, which pose huge challenges for investigators (and governments). I wrote about some of these issues last October in a post titled, "Ebola vaccine - do we really need a placebo-controlled RCT." In the post, I described a stepped-wedge design, which we've used in health services research, but I made clear that I wasn't a vaccine trial expert.

Fortunately, more experienced vaccine trial experts have just published their thoughts on designing vaccine trials during emergencies with the ongoing West African Ebola outbreak providing context. Marc Lipsitch, Rebecca Grais and colleagues (COI - I'm a co-author), suggest three principles worth considering when designing vaccine trials during public health emergencies:

Principle 1: Block Randomization within small centers with analysis matched by center
    Some centers may have higher (or lower) incidence, so that it is better to randomize within a center (block randomization). In this way, exposed (vaccinated) and unexposed (controls) would be expected to have similar risk of infection.

Principle 2: Stepped Rollout
     This principle is a response to the urgency of the situation. An individual randomized trial would require waiting for all centers to come online before commencing a trial (see purple box in Figure A, above). In contrast, a stepped role-out allows each center to commence the trial as soon as they are ready (purple area in Figure B, above).

Principle 3: Adaptive Design
     Since vaccine trials require participants to be at some risk of infection after the've established immunity from vaccination, it is imperative to know if centers will have active transmission once they are included in the study. This is incredibly difficult to predict. Adaptive designs use pre-specified rules to add centers (green in Figure B) or extend follow-up periods (yellow in Figure B), which improve the chances that a trial will reach a successful conclusion.

There is more depth in the Science Policy Forum, if you're interested. A final note of thanks to Marc and the group for including me in this effort. I learned a great deal through many email discussions over the past 4-5 months.

For every rule, an exception

The current Ebola virus disease (EVD) epidemic has repeatedly confirmed a stark “gradient of infectivity”. On the one hand, those severely ill with EVD represent transmission risks so high that safe care can only be provided in the most well-prepared treatment units. On the other hand, those with few or no symptoms of EVD represent nearly zero transmission risk. The best evidence for this is that there have been over 850 health care worker EVD cases (and almost 500 deaths) since the beginning of this epidemic, yet of the several hundred community contacts of cases in the US, UK and Spain, there hasn’t been a single transmission event outside of an intensive care unit.

Thus the rule I’ve heard, and stated, at various times during the epidemic: “no symptoms, no transmission risk.”

Now the exception: sexual transmission. We’ve long known that filoviruses can be detected in semen for weeks and even months after disease recovery (a 1995 study reported Ebola virus RNA in seminal fluid for up to 101 days, and infectious virus up to 82 days, and in 1968 the sexual transmission of Marburg virus was reported 13 weeks into convalescence). Now a concerning case in Liberia has the WHO recommending indefinite safe sex practice for EVD survivors. From the New York Times article:

"The new guidelines came one day after the death of Liberia’s single confirmed patient with Ebola, Ruth Tugbah. Before her illness, the country had gone three weeks without a new Ebola diagnosis, and hopes had risen that Liberia was nearing the end of a yearlong epidemic that killed more than 4,000 people there. Ms. Tugbah’s only known risk factor was having a boyfriend who was an Ebola survivor. 

Scientists detected the genetic material of Ebola from a semen sample the boyfriend provided to infectious disease investigators, officials from two Ebola response agencies said, speaking on background because they were not authorized to speak publicly."

If further investigation confirms this transmission event, it would indicate that she was infected several months after his recovery from EVD (more than the three months currently suggested as the maximum time virus may be present in semen). Given the sheer number of cases that have occurred in the affected countries, this poorly-understood sexual transmission risk adds an unwelcome twist as the outbreak winds down.

Post-exposure Vaccination for Ebola

The ongoing Ebola virus outbreak in West Africa continues to underscore the importance of a strong international public health infrastructure and continued investment in both basic and clinical research targeting infectious pathogens. The first line of defense for infectious diseases, if available, is a safe and effective vaccine. However, approved vaccines do not exist for many pathogens like Ebola, so well-designed personal protective equipment becomes critical. But even the best available PPE can't protect us from sharps injuries. Which brings us to a fascinating case report of post-exposure vaccination of a physician with a needlestick injury obtained while working in an Ebola treatment center in Sierra Leone.

The report by Lilin Lai and colleagues was just published online in JAMA along with a very well-written editorial. The 44-year-old physician from the US was stuck by an 18-guage hollow-bore needle through two layers of gloves after caring for Ebola patients with very high viral loads. Because doffing procedures had to be followed, there was a 10-minute delay in cleaning the wound with bleach, soap/water and CHG. The patient was evacuated and while boarding the jet received an experimental vaccine - a first-generation recombinant vesicular stomatitis virus–based Ebola vaccine (VSVΔG-ZEBOV) - 43 hours post-exposure.

Post-vaccination, he developed fever and malaise but made it safely to the NIH Clinical Center for further care and evaluation. His course was a bit rocky the first few days with fever, lymphopenia and diminished O2-sats but symptoms and signs slowly improved over 3-5 days and he was asymptomatic by day 7. He was discharged to complete the 21-day mandatory isolation-period at home. Ebola virus was never detected.

You can read the full report (free online) if you're interested in the many tables and figures outlining his immune responses. Briefly, the vaccine did elicit a strong innate and virus-specific immune responses. Most importantly (per the editorial) it was "able to induce an IgG antibody response against the Ebola virus glycoprotein at a level that has been associated with protection of nonhuman primates." However, the editorial correctly notes that no definitive conclusions can be drawn since it is unclear if the patient was ever infected with the virus and the adverse events the patient experienced could have been secondary to his concurrent travelers diarrhea.

What is important is that while numerous candidate Ebola vaccines have been shown to effectively prevent transmission in nonhuman-primate models, post-exposure treatments and vaccines have been harder to develop. I wonder if a trial seeking to reduce sharps injuries in Ebola-treatment settings is in the works or if NIH would fund such a trial? Last time I checked, sharps injuries were on the rise, so investment in prevention research remains critical.

image source: wikipedia

Krampus visits Atlanta

The CDC has taken a lot of heat this year, about lab snafus involving anthrax and avian flu, and about some early problems in Ebola response. Now we have front page stories about another lab error—live Ebola virus mistakenly sent from a BSL-4 to a BSL-2 lab environment, at least according to the NY Times account. I’m sure there is more to this story, but the incident has already resulted in another loud chorus about CDC’s failings. Like Krampus, the anti-Santa of Bavarian legend who comes to punish naughty children, many will want to sanction CDC. 

That would be a mistake. Krampus should instead visit Washington DC, and severely punish the politicians who consistently underfund the CDC. I agree that CDC needs to improve the safety culture in their laboratories, and hold people accountable for following established procedures. They are working on that. The saddest part, to me, about these incidents is that they always garner far more attention than the hundreds of things that the CDC does right every day, and that are essential to protecting the public health. The challenges faced by CDC get larger every year (Ebola, MERS-CoV, Enterovirus D68, carbapenemase producers, and on and on). Yet the budget trend (see below and online) is in the other direction. I hope Santa eventually brings CDC a larger budget, while Krampus stays busy on Capitol Hill.

GBV-C Co-Infection Associated with Improved Ebola Survival

GB virus C (GBV-C or Human Pegivirus - or even Hepatitis G) is associated with high viremia but there is little evidence that it causes disease in humans. Back in 2001, Jack Stapleton and colleagues (including Dan) showed that GBV-C co-infection significantly improved survival in HIV+ patients. The thought behind this association is that GBV-C attenuates aberrant immune activation.

Given that GBV-C infects between 10-28% of individuals in the three countries that have experienced the highest level of Ebola infections in the recent outbreak, Michael Lauck and colleagues in Madison wanted to examine the influence of GBV-C co-infection on Ebola outcomes. Using a cohort of 49 Ebola infected patients with outcome, age and gender data available they assessed the association of GBV-C co-infection on mortality.

Overall, mortality in the cohort was 69%. However, while mortality was 78% (28/36) in GBV-C negative patients, it was "only" 46% (6/13) in GBV-C co-infected patients. The unadjusted and adjusted analyses are in the Table below. The higher p-value with unchanged OR in the multivariable model likely represents a loss in power and not age-related confounding as the authors claim. Minor quibble - they presented a case-control (OR) analysis for this cohort of patients with a significant p-value. Analyzed as a cohort study, the RR=0.59 (0.32-1.09), p=0.0950. Either way, if I had Ebola, I'd also want GBV-C.

Wanted: Ebola test with perfect negative predictive value at time zero

The tragic death of Dr. Martin Salia has triggered a spate of news articles about the limitations of Ebola diagnostic testing. According to news reports, Dr. Salia tested negative twice early in his symptomatic period, and was already quite ill by the time he tested positive.

The fact that the most sensitive Ebola virus diagnostic test (PCR applied to a blood sample) may not be positive until 3 days after symptom onset is well known, however. The reason for this has to do with the pathogenesis of Ebola virus infection. The point of entry and initial replication for Ebola is the “dendritic” cell. Present in large numbers in the skin, mucosa and intestinal lining, dendritic cells are sentinels, guarding the interface between the human immune system and a hostile environment. They encounter invaders, engulf them, and present their antigens to cells of the adaptive immune system. Dendritic cells carry the virus to lymph nodes and other organs of the “reticuloendothelial system” (liver, spleen). So before the virus reaches detectable levels in the blood, there may be hours-to-days of replication in these cells and organs, along with symptoms of fever and fatigue. A test, even a very sensitive test, that is applied to blood will not detect the virus until it appears in the bloodstream in larger numbers. 

This lack of a rapid and accurate diagnostic test early in the Ebola disease course is a major problem—not only for early initiation of therapy for those infected, but also for the management of “persons under investigation” (who may require Ebola-level isolation precautions for several days while awaiting a negative test that has been taken at least 3 days after symptom onset). 

But this problem plagues infectious diseases diagnostics generally. As this recent Lancet ID article points out, the lack of early and sensitive diagnostic testing is one reason why so many patients in our hospitals receive days of unnecessary antimicrobials. More on this study later, perhaps from Eli, one of the authors!

Image by Sean Gallup, Getty Images

Getting to zero

By my count, there are now zero persons in the United States who are actively infected with Ebola virus.  This is the perfect time to donate your time or your money to Ebola response in West Africa.

Also, Kaci Hickox still doesn't have Ebola. She should be allowed to go bowling.

Finally, one observation about our weirdly, uniquely American response to Ebola virus. The CDC Guidance for Monitoring and Movement Restriction treats healthcare workers who have "direct contact while using appropriate personal protective equipment (PPE) with a person with Ebola" differently based upon whether they were caring for patients in countries with or without "widespread Ebola transmission". Thus brave volunteers returning from West Africa are under more stringent monitoring and movement restriction guidance than are those who might care for a patient in New York, Texas or Iowa. Yet if you compare the ratio of 'healthcare worker acquisitions/Ebola infected patients' in the US versus West Africa, I'm not sure there is any contest (2 acquisitions/9 Ebola patients = .22--what's 22% of 13,268, the total number of cases thus far in West Africa?).  This isn't an argument to be more restrictive about those who care for Ebola patients in the US, it's an argument to chill the #&*% out about humanitarian healthcare workers returning from the outbreak zone.

SHEA Supports Evidence-Based Measures to Prevent Ebola Transmission, Opposes Mandatory Quarantine for Healthcare Personnel

FOR IMMEDIATE RELEASE: CONTACT: October 26, 2014 Kristy Weinshel, 703-684-1008 kweinshel@shea-online.org

ARLINGTON, Va. (October 27) – The Society for Healthcare Epidemiology of America (SHEA) remains deeply concerned about the Ebola virus disease (EVD) outbreak. The recent news about Dr. Craig Spencer’s infection, along with the infections of the many other healthcare personnel (HCP) who have risked their lives to provide care during this tragic outbreak, illustrates how difficult it is to protect HCP serving patients with severe EVD.

SHEA supports the recent infection prevention guidance issued by the Centers for Disease Control and Prevention (CDC), and the commitment healthcare facilities across the country have made to train and prepare their teams for the care of patients with EVD.  SHEA continues to support the rigorous application of evidence-based measures to prevent EVD transmission. Based upon the strong evidence that Ebola is not transmitted by those who do not have symptoms of EVD, we do not support mandatory quarantine of individuals, including HCP, who have provided care for patients with EVD.  Our concern is about both the ramifications for HCP returning from West Africa and the potential application of this quarantine to all HCP caring for patients with EVD.  SHEA believes that mandatory quarantine will lead to fewer volunteers and increased difficulty in assembling care teams in West Africa and in other countries, including the United States, preparing to care for EVD patients.

SHEA and its membership of infection control and prevention experts support the active monitoring (twice daily, for fever and symptoms of EVD) of all HCP providing care for EVD patients, including returnees from Ebola outbreak areas in West Africa. Mandatory quarantine should only be implemented for those who do not adhere to such monitoring.

SHEA continues to work with the CDC and all relevant stakeholders to ensure the safety of HCP and to promote positive outcomes for those who contract Ebola. 

###

SHEA is a global professional society representing more than 2,000 physicians and other healthcare professionals with expertise and passion for healthcare epidemiology and infection prevention to improve patient care in all healthcare settings. SHEA's mission is to prevent and control healthcare-associated infections and advance the field of healthcare epidemiology. The society advances its mission through advocacy, science and research, expert guidelines and guidance on key issues, the exchange of knowledge, and high-quality education.  SHEA focuses resources on promoting antimicrobial stewardship, ensuring a safe healthcare environment, encouraging transparency in public reporting related to HAIs, focused efforts on prevention and more. 

Visit SHEA online at www.shea-online.org, www.facebook.com/SHEApreventingHAIs and @SHEA_Epi

link to SHEA press release: http://www.shea-online.org/View/ArticleId/318/SHEA-Supports-Evidence-Based-Measures-to-Prevent-Ebola-Transmission-Opposes-Mandatory-Quarantine-for.aspx

Bowling Alone

The big news tonight is that the governators of New York and New Jersey decided to institute quarantine for everyone returning from West Africa after having contact with Ebola patients. This decision was driven by political considerations, including the costs (in time and money) expended due to the decision to do extensive contact tracing around Dr. Craig Spencer’s movements in New York City since 7 am on Tuesday, October 21.

Nothing that has happened during this tragic Ebola epidemic has called into question this simple fact: Ebola is not transmitted in the absence of symptoms. Nor is it transmitted to casual or household contacts during early infection. Consider Mr. Duncan, sent home from the hospital with fever, spending the early days of his Ebola illness with almost 20 close contacts (mostly family members), until he was finally taken back to the hospital after vomiting “wildly” in an apartment complex parking lot. Let’s count the community and family transmission events: ……..ZERO. 

Careful monitoring of symptoms and signs (fever) is sufficient for early detection of symptomatic Ebola infection and prevention of community transmission. Movement restrictions, including strict home quarantine, provide no additional benefit. The adverse consequences of misguided quarantine of caregivers are clear, however: fewer providers willing to assist in the outbreak area, and fewer providers willing to volunteer to join Ebola care teams in US hospitals, complicating preparedness efforts. If Ebola providers returning from West Africa are quarantined, how can we not also quarantine US healthcare workers who provide care for Ebola patients? How will such providers commute to work, if they depend upon public transportation? Conversely, how will we convince anyone to participate in care, if they cannot return home to family for the duration of caregiving (+ 21 days)?

Don’t take it from me, though. Listen instead to an infectious diseases doc who’s been fighting the outbreak in Sierra Leone:

Dan Kelly, 33, an infectious disease doctor and a founder of Wellbody Alliance, a nonprofit organization working in Sierra Leone, criticized the governors’ response as knee-jerk. 

“I think we are just digging the grave deeper,” he said in a telephone interview from Freetown, the capital. “Come on, that’s exactly the move to push people away from going to Sierra Leone and other affected areas. It’s going to escalate the epidemic and not help solve the crisis."

He added: “If we’re going to get in front of it, we need health care workers from abroad. They cannot feel shunned or discriminated against.”

Morebola

The news tonight about Dr. Craig Spencer, an MSF volunteer who recently returned from caring for Ebola patients in Guinea, is sobering for several reasons. There are many details to come, but I thought I’d post a few quick initial thoughts (or reminders) about how this tragic development should, or shouldn’t, change the way we think about the Ebola virus outbreak:

This outbreak is occurring in West Africa. Not in the US. West Africa. The level of hysteria in the US is directly proportional to the number of Ebola patients on US soil, but we should never forget, even for a minute, that the outbreak continues to rage in Liberia, Sierra Leone, and Guinea (where Dr. Spencer acquired the infection). This widely cited Lancet modeling study suggests that 2-8 Ebola infected individuals will board planes monthly during their incubation period. Thus the best way to combat Ebola in the US is to mobilize resources for West Africa.

In the US, those at risk for Ebola are healthcare workers who have cared for Ebola patients (whether here or in West Africa). Not mall-goers, bowlers, subway riders, or those who might have been in an airport terminal on the same day as an asymptomatic Ebola patient. The greatest transmission risk is borne by those who provide direct care for Ebola patients during severe illness, when viral shedding is very high. 

There may be no way to reduce Ebola transmission risk to zero in healthcare settings, given the current state of Personal Protective Equipment technology. Dr. Spencer reported no breaches in the MSF protocols, which are widely recognized as the most stringent (and effective) in use. Healthcare workers have always accepted some risk in provision of healthcare, and Ebola reminds us that the risks can be grave, and that healthcare workers willing to bear these risks are heroic.

This case may make it far more difficult to assemble care teams for suspected or confirmed Ebola patients. Not just because we have yet to determine how Nina Pham, Amber Vinson, Craig Spencer, and several other caregivers were infected, but because this case could result in more stringent protocols regarding self-monitoring and movement restriction (quarantine) for those willing to care for Ebola patients. Healthcare workers who learn they may be required to restrict their movement during the entire time they care for patients (and 21 days thereafter) may be less likely to step forward. 

All eyes now will be on Bellevue. If Dr. Spencer receives all of his care at Bellevue rather than being transferred to one of our four federally-funded and designated biocontainment facilities, the hypothesis that any well-prepared hospital can safely care for an Ebola patient will again be tested.

Photo credits: Facebook; Bryan Smith

Ebola: N=2, Now What?

A lot of us woke up again to the horrible news that yet another health care worker in Dallas has acquired Ebola from the index patient during patient care. There are a lot of accusations flying around most of which will prove misleading or unfounded and some others might be true. We do not know. My sense of the situation is that what we learned from the first transmission still applies. We have further evidence that the standard way of wearing droplet/contact precautions during routine care of patients with pathogens like MRSA or Acinetobacter is ineffective in protecting health care workers.

Each hospital with an ICU must develop infection prevention training teams that utilize existing PPE protocols or adapt them to their local PPE supplies (e.g. their unique gowns, masks or PAPRs). These training teams must initially target experienced ICU nurses and physicians and this training must occur before any patients with Ebola can be cared for in their hospitals. You can't just practice this once. Most of us who have tried donning and doffing have failed to do it correctly the first time. We failed when there was no stress and no risk and will be much more likely to fail when focusing on the care of a sick patient. Once these trained cohorts of health care workers are established, they should be organized into buddy-teams. For example, while one trained ICU nurse provides care, another is watching his every move from donning of PPE, to caring for the patient, to doffing of PPE. The buddy must be in PPE themselves. The buddy's job is to be the second "infection control" brain for the nurse focusing on the clinical care. It is simply impossible to focus on critical care and PPE at the same time. Let's implement a system for success.

A final note today: I want to acknowledge the many many infection preventionists, hospital epidemiologists, ICU nurses, critical care physicians, emergency department staff, environmental services staff and the many unnamed others who are working tirelessly to prepare their hospitals. Most of their hard work will go unnoticed. Most of their hospitals will never care for a patient with Ebola but they are the backbone of our health care system. So, thank you!

Ebola: Bloggers in the News

UPDATED October 19

Last night, Dan, Mike and I sat around a table and drafted an op-ed at the suggestion of several colleagues. We would eventually like to include it here, but that will have to wait pending editorial reviews and rejections. Media requests have been frequent and we are doing our best to speak with as many reporters as we can. Dan has been very busy with SHEA duties, as he is currently the Society President. SHEA has just released a statement on infection prevention funding needs where Dan is quoted. He spoke (audio below) this morning on NPR-KPCC in Southern California and also appeared on NBC Nightly News. He also was quoted in USA Today.

Mike spoke to Iowa Public radio about what we've learned from the transmission of Ebola to healthcare workers in Iowa and what we can do to prepare. He also appeared on MSNBC.

I've done several interviews, including one with Bloomberg News yesterday (I didn't write the headline) and a few more that are scheduled to appear. I've also posted an MP3 below of an interview I did with CBS radio out in LA (KNX 1070) yesterday. I tried to emphasize the importance of PPE protocols, particularly doffing and the need for a buddy to monitor every step. Buddy is my new favorite word.

Perencevich Interview on CBS KNX - LA

Diekema Interview of NPR KPCC - So Cal

Ebola: What can we learn from an N of 1?

Most of us woke up to the very unsettling news that a health care worker had acquired Ebola during the care of the index patient in Dallas. Those following the blog know that we've been worried about just this type of event since July, when Mike provided an Ebola primer. Specifically, we've been worried about the complexity of the PPE required and how this could paradoxically increase risks to health care workers. We've also highlighted the massive WHO budget cuts, CDC cuts and Prevention and Public Health Fund cuts since at least 2012.

In addition to the national cuts, individual hospitals have seen reduced support for infection control programs just as more and more is being asked of them. It used to be that hospital epidemiologists and infection preventionists could do surveillance rounds on the wards and educate from-line staff. Now, many hospitals have barely enough staff to complete their surveillance and public reporting duties leaving many trapped at their desks analyzing data. There is zero excess capacity to educate clinical staff on basic infection prevention practices like contact precautions. At many hospitals there is no capacity to add additional training in Ebola PPE protocols. As Marc-Oliver Wright said to me once: "You can't fight and prepare for the maybe (insert scary virus) when the required was due yesterday." Yet many hospitals are managing by shifting staff away from MRSA, away from CLABSI and away from influenza, which leaves our patients vulnerable to these more likely threats. If this were the military, there would be claims about fighting with one hand behind our back. That's the case here - we are fighting a war against Ebola and we've got an un-gloved hand behind our back.

So what are the lesson's from Dallas?

First, PPE is not 100% effective with current technology and training protocols. If health care workers auto-contaminate their hands when removing gloves 11% of the time when they caring for VRE colonized patients and 4.5% of the time when caring for patients with Acinetobacter, there is little room for error in PPE removal and hand hygiene when caring for patients infected with Ebola, particularly near the end of their disease course.

Second, the focus of Ebola preparedness in the US has to be 100% directed towards hospitals, initially the ICU settings. It's a simple fact that patients aren't infectious until after they develop symptoms and they are highly infectious once they are in shock in the ICU. Each and every hospital must walk through PPE donning and doffing and plans for Ebola patient care. They must train a cohort of doctors, nurses and environmental services staff now. Practice, Practice, Practice. Once the ICU staff are trained, the net should be widened to include the emergency department and other clinical settings. Work backwards from the highest risk settings where patients are most infectious (e.g. ICU) to the least.

Third, we need to demand funding for infection control in our hospitals. Double the number of infection preventionists and make sure each hospital has an Infectious Disease trained physician responsible for ensuring that all infection prevention protocols are followed. If we aren't even prepared for Ebola, how will we ever be prepared for a far more infectious avian influenza or MERS?

Fourth and finally, we must increase national funding for infection prevention. We must develop new PPE technologies and new methods to improve compliance and education. Right now we are using ancient technology - gloves, gowns, masks. We must also fund local and regional public health departments, as well as CDC, WHO and the PHEP, whose funding has been cut if half since 2006 (see below). We might get lucky with Ebola in the US (sadly it continues to get worse in Africa), but I doubt we'll be so lucky with the next virus.

***And for reading beyond the events of today, I suggest reading Judy Stone's excellent post on the problems with politics and public health mixing. She's covered many of the same topics that I've mentioned but with a broader scope.

Traveling With Ebola Is Not Traveling With Influenza

With everyone away at IDWeek, I've had time to think about Ebola and things like airport screening programs. I'm not supportive of outright travel bans. As many have eloquently said, bans will do more economic harm than good and hinder efforts in West Africa. However, I'm worried that we might be equating Ebola with Influenza. Many of the discussions concerning travel restrictions and Ebola spread have centered around models and estimates derived from respiratory viruses epidemics like the 2009 H1N1 influenza pandemic. Yes, influenza and Ebola are both viruses, but that's like equating a sparrow and an Allosaurus because they're both dinosaurs.

The first and perhaps most important difference between the current Ebola outbreak and the the 2009 H1N1 pandemic is that Ebola it is very slow moving. For example, the first case of Ebola is thought to have occurred 307 days ago on December 6th in a two-year old boy. Since that time there have been an estimated 8,032 cases (granted these could be underestimates). If you compare a similar 307-day period for 2009 H1N1, April 12, 2009 to February 12, 2010 CDC estimated that between 42 million and 86 million cases occurred in the US with a mid-level estimate of 59 million people infected. Think about that - 7300 times more cases of H1N1 using the mid-level estimate during the same 307 days.

Another difference between influenza and Ebola is the incubation period (time from exposure to symptoms). Generally, the incubation period for influenza is 1-4 days (2-day average). For Ebola symptoms appear 2 to 21 days after exposure with an average of 8 to 10 days.

A final difference between Ebola and 2009 H1N1, which seems to be overlooked in discussions of airport screenings and other control measures, is infectivity during the incubation period. Put another way, can you transmit the virus without knowing you are sick? With Ebola, humans are not infectious until they develop symptoms. In comparison, with 2009 H1N1 it's reported "that pre-symptomatic influenza transmission occurred via both contact and respiratory droplet exposure before the earliest clinical sign, fever, developed" in a ferret model. This finding has been confirmed in humans. Interestingly, SARS is not infectious prior to symptom development (see CDC and Zeng et al), which may explain why we were ultimately able to contain SARS (unlike influenza).

To summarize, Ebola is slower moving, has a much longer incubation period (especially compared to the duration of a transcontinental flight), and is not contagious before symptoms develop. What does this mean? It means that if Ebola was as infectious as influenza, millions would have already died - apocalypse. It also means that since Ebola is not transmissible during its long incubation period, it may be possible to quickly isolate patients when symptoms develop. Thus, airport screening on exit or entry could limit transmission and perhaps through early diagnosis allow Ebola infected patients to receive life saving treatment more quickly.

A more concrete example: Imagine a person infected yesterday with influenza but still asymptomatic during their two day-incubation period. This person would screen negative overseas and in the US. However, it's highly likely that they are already infectious or will become infectious during their flight. Thus, many other passengers in the airport and plane would take influenza home with them as a vacation souvenir. Screening doesn't work for influenza. This would not be the case with Ebola because they will detect their symptoms as they become infectious and only spread it though blood exposure - something unlikely so early in the infection even on a long transcontinental flight. And think about how many times another person has bled on you even when they were bleeding (i.e. the Ebola condition) versus how many times someone has coughed or sneezed on you when they were coughing and sneezing (the influenza condition). **cough**

Airport screening for Ebola symptoms may still be ineffective, but I would like to see a few more mathematical models analyzing the epidemiology of Ebola and the impact of specific screening programs. In the meantime, let's focus our attention and resources on the horrible plight in West Africa.

image source: xkcd

Ebola: Doc from Oklahoma City Calms the State of Texas

Many of you might not know that Kent Sepkowitz, while living and practicing in NYC, hails from the great state of Oklahoma. So when Stephen Colbert went in search of an infection control expert with Red-River roots, he couldn't do much better than our esteemed colleague, just a taxi ride away. If you're still left wanting more after watching this video, head on over to NPR to hear one of the better discussions of Ebola with Kent and Scott Simon from Weekend Edition. 

Ebola Screening: Hey CDC! Is it an AND or an OR?

Like many of you, we've all been assisting with Ebola planning for the past several months. Just today, Mike and I were in another planning meeting and the subject of our screening algorithm came up. Mike had noticed that the September 4th CDC Definition of Person Under Investigation (PUI) that we've been using: "fever of greater than 38.6 degrees Celsius or 101.5 degrees Fahrenheit, AND additional symptoms such as severe headache, muscle pain, vomiting, diarrhea, abdominal pain, or unexplained hemorrhage" is now different in the PDF algorithm that the CDC posted on October 2nd. It now says "FEVER OR EVD symptoms." I've included the relevant portion of the PDF algorithm above.

This may seem like a minor change, but for many facilities it will be a big deal. To go from a relatively sensitive "fever AND" to a very sensitive "fever OR" is not a small change. This may require EDs and clinics to screen additional patients and result in a large increase in laboratory tests being sent for Ebola diagnosis. I think that CDC meant to suggest that fever is enough to prompt a travel history, but now anyone with fever, headache, weakness, muscle pain, vomiting, diarrhea, abdominal pain or hemorrhage will also need to be asked a travel history. In practice this will mean that every patient that walks into an ED or clinic should be asked a travel history first and then asked about symptoms. I'm not convinced this should happen and feel much more comfortable with having symptoms guide travel history. But since almost any general complaint is now included, we may be left with no other choice but to ask travel history first. And of course, we don't know what CDC wants us to do since both documents are live and offer conflicting advice.

So, which is it CDC?  Is it an AND or an OR?

Guest Post: The Danger of Ebola

This is a guest post by Philip Lederer, an ID fellow at Massachusetts General Hospital and Brigham and Women’s Hospital. He was a CDC Epidemic Intelligence Service officer and has also worked in Mozambique as clinical director of the UCSD-Maputo Central Hospital Educational Collaboration.

The danger of Ebola goes well beyond the thousands of cases reported so far in Liberia, Sierra Leone, Guinea, and neighboring countries. It goes beyond the models which estimate that up to 1.4 million cases could occur by next year (1). The danger doesn’t have to do with Ebola becoming airborne or spreading widely across the United States. 

Ebola is still centered in West Africa, and the danger is of collateral damage. Malaria control programs have shut down in the 3 countries, according to a recent report (2). Cholera could reemerge, as there was a 2012 outbreak in Sierra Leone (3). People are losing their jobs. Starvation and violence could kill many more people than the Ebola virus. It’s time for the world to act.

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References:
1) Meltzer MI, Estimating the Future Number of Cases in the Ebola Epidemic — Liberia and Sierra Leone, 2014–2015 http://www.cdc.gov/mmwr/preview/mmwrhtml/su6303a1.htm?s_cid=su6303a1_w


2) Hayden EC, Ebola outbreak shuts down malaria-control efforts http://www.nature.com/news/ebola-outbreak-shuts-down-malaria-control-efforts-1.16029

3) Nguyen VD et al, Cholera epidemic associated with consumption of unsafe drinking water and street-vended water--Eastern Freetown, Sierra Leone, 2012. http://www.ncbi.nlm.nih.gov/pubmed/24470563

Ebola and WHO budget cuts

Anthony Harris used to (and may still) include this New Yorker cartoon in his antibiotic resistance talks. I've always thought it summed up the resistance crisis quite well. We don't have effective antibiotics, so we must resort to the ridiculous. One of the major reasons we lack new classes of antibiotics is the lack of public funding for basic research of bacterial pathogens. It's pretty simple really. Years of ignoring the problem have us in this situation and it will take many years of reinvestment to build up the laboratory and professional resources needed to be fully engaged in antibiotic discovery.

A similar situation has played out in public health preparedness. I encourage you to read Dan's posts (here and here) covering the Prevention and Public Health Fund. And it's not just the US. In the Guardian today, Peter Piot - the discover of Ebola, expressed his fears that the outbreak is out of control. It's an amazing account of how he discovered and named the virus. It also highlights the almost tragic accidents that occurred in his lab, yet no one caught the virus. When asked why the WHO responded so late to the Ebola outbreak in Africa, he responded:

"On the one hand, it was because their African regional office isn't staffed with the most capable people but with political appointees. And the headquarters in Geneva suffered large budget cuts that had been agreed to by member states. The department for haemorrhagic fever and the one responsible for the management of epidemic emergencies were hit hard...I think it is what people call a perfect storm: when every individual circumstance is a bit worse than normal and they then combine to create a disaster. And with this epidemic there were many factors that were disadvantageous from the very beginning."

I'm not a military historian, but this situation seems terribly similar to what I've read about simultaneous wars on two fronts. Although in public health, it can be four or five fronts. We have Ebola, MERS, avian influenza and Enterovirus D68 knocking on our doors (and I'm sure I left out a few.) These are all on top of the CDC and WHO's "day jobs" fighting foodborne outbreaks, antibacterial resistant bacteria, TB, HIV and malaria (and I'm sure I left out many). Long term cuts to public health infrastructure can't be repaired in one month or one year. You can't go buy extra diseases detectives quickly off the shelf much like you can't quickly buy an extra aircraft carrier. We can already see how outbreaks respond to intensive budget cuts.

image source: Conde Naste

Ebola: Hospital Epidemiologists in the News

It's been amazingly active week for hospital infection control with adult deaths and paralysis in children linked to Enterovirus 68 and there have also been some issues with Ebola. Practically every Hospital Epidemiologist* has been called upon to explain the transmissibility of Ebola and describe how they've been planning to protect healthcare workers and the community. Of course, I can't possibly list all of the mentions in local, national and international media, but if you have a particular clip that you'd like us to post, let us know.

I've been impressed by the clarity and skill that my SHEA colleagues have demonstrated. For example, earlier today Dan was on Public Radio International (PRI) discussing the difference between the virulence and contagiousness of infections and how it's easy to confuse the two. Specifically he said "In the case of Ebola, it is not true that it is airborne, it's not true that you can catch it just by being in the same room as an infected person. It really does require direct contact." Head on over to PRI, to hear the whole interview.

Kent Sepkowitz was on CNN yesterday describing the contagiousness of Ebola with the money quote: "so the super contagious body compartment is blood and it's blood and it's blood." And one of the stalwarts of hospital epidemiology and mentor to many, Leonard Mermel, was on MSNBC's All in With Chris Hayes tonight describing the well-developed screening algorithm that's been implemented at Rhode Island Hospital. I've added the video below. If you want to jump directly to Len Mermel's discussion, it occurs around 12:00. (apologize for the brief ad)

*A hospital epidemiologist is typically an infectious disease physician specialist who develops infection control plans to protect patients and healthcare workers in clinical settings including acute care hospitals and long term care facilities. During outbreaks the hospital epidemiologist helps identify the source of the infection and determines how best to contain its spread. They educate clinicians about the optimal ways to prevent infections (e.g. hand hygiene), while also tracking the use and misuse of antibiotics and the emergence of antibiotic-resistant bacteria. Other goals include preventing post-operative surgical wound infections and infections associated with central venous catheters. They are each hospital's very own disease detective!