Ebola: worldwide dissemination risk and response priorities/ The Lancet

This piece in the Lancet, authored by Cowling and Yu, discusses issues of Ebola dissemination and means to reduce spread to other countries.  Its final paragraph discusses what we do not yet know, but need to learn:

There are several important near-future research needs. Perhaps most urgent is a better understanding of the effectiveness of existing treatment options, including convalescent serum. In the medium term, it is hoped that new vaccines and drugs will be available quickly for human clinical trials and in exposed populations.8 The WHO Ebola Response team has neatly summarised the transmission dynamics and epidemiological characteristics including the reproductive number, incubation period, and case fatality risk in the current Ebola virus outbreak,1 but one important unknown is the proportion of infections that are asymptomatic or mildly symptomatic. If mild infections do occur and are infectious, disease control outside west Africa might be increasingly challenging. However, this scenario is thought to be unlikely.9 One particularly pressing need is for the reassessment of appropriate procedures for infection control, and the potential for the virus to spread via small particle aerosols10 in addition to via contact with infected patients or their bodily fluids. Infection of health-care personnel in west Africa is often attributed to the scarcity of appropriate protective equipment and supplies, or inadequate administrative controls.11, 12 However, the nosocomial cases in Dallas and Madrid have raised the concern that present protocols might not be sufficient to protect health-care personnel fully against infection, particularly if cases are managed in health-care facilities that are not fully prepared.

Readers note:  CDC improved its infection control PPE recommendations the evening of Oct 20, making them virtually equivalent or better than the SARS protocols. (SARS spread by the respiratory route.)  They now include respiratory droplet precautions. This piece was published online Oct. 21.  I believe the current CDC recommendations provide health-care personnel with as good protection as currently achievable using available PPE.

Why is Ebola droplet spread controversial, when CDC, NIH and WHO have long acknowledged it?

From CDC regarding how one must handle laboratory specimens from someone with Ebola:

"Clinical specimens [such as blood or urine] from persons suspected of being infected with one of the agents listed in this summary (Ebola is listed as BSL-4 on page 251) should be submitted to a laboratory with a BSL-4 maximum containment facility."  (on page 238) "The recommendations for viruses assigned to BSL-4 containment are based on documented cases of severe and frequently fatal naturally occurring human infections and aerosol-transmitted laboratory infections" 

From CDC regarding air travel and Ebola:

When providing direct care to a sick traveler who came from a country with an Ebola outbreak, also wear surgical mask (to protect from splashes or sprays), face shield or goggles, and protective apron or gown... Give a surgical mask if a sick traveler is coughing or sneezing, if the sick person can tolerate wearing one.

From CDC regarding generation of aerosols in hospitals treating Ebola patients:

Aerosol Generating Procedures

Conduct the procedures in a private room and ideally in an Airborne Infection Isolation Room (AIIR) when feasible. Room doors should be kept closed during the procedure except when entering or leaving the room, and entry and exit should be minimized during and shortly after the procedure.
     HCP should wear appropriate PPE during aerosol generating procedures.
Conduct environmental surface cleaning following procedures (see section below on environmental infection control).

From CDC regarding the need to use Personal Protective Equipment (PPE) that can protect against aerosol and airborne virus:

...A PAPR with a full face shield, helmet, or headpiece. Any reusable helmet or headpiece must be covered with a single-use (disposable) hood that extends to the shoulders and fully covers the neck 

From WHO:

Theoretically, wet and bigger droplets from a heavily infected individual, who has respiratory symptoms caused by other conditions or who vomits violently, could transmit the virus – over a short distance – to another nearby person.

This could happen when virus-laden heavy droplets are directly propelled, by coughing or sneezing (which does not mean airborne transmission) onto the mucus membranes or skin with cuts or abrasions of another person.

From NIH's NIAID:

BSL-4 agents "cause illness by spreading through the air (aerosol) or have an unknown cause [sic] of transmission" 

CDC took down its poster on aerosol spread--but here it is

We Are Ignoring the US' $440 Million Surge Capacity for Ebola vaccine production

Ebola is killing 60-70% of those affected, even with treatment.  Manufacturers say it will take quite a while to produce sufficient supplies of a vaccine, and that bulk manufacturing will only begin after one of several vaccine candidates is chosen. This makes no sense. The US government spent $440 million to help 3 companies develop surge facilities to manufacture drugs and vaccines for exactly this type of epidemic. Here's what DHHS claims it can do--but it isn't doing this:

Since 2010, HHS has taken steps to increase national vaccine manufacturing capacity with nimble and flexible technologies, such as cell-based vaccine technologies. These technologies may assist HHS in providing more pandemic influenza vaccine sooner. Cell-based vaccine production could more easily meet surge capacity needs because cells could be frozen and stored in advance of an epidemic, or developed rapidly in response to an epidemic.

Furthermore, vaccine manufacturers gear up each year to produce hundreds of millions of flu vaccine doses, when their degree of efficacy is a huge question mark.

What needs to happen is that the top candidate (currently 3) Ebola vaccines should be produced starting now in these surge facilities.  That way, once they have been tested, there will already be a stockpile to begin using. Alternatively, stop making some flu vaccines (almost no country besides the US has a universal flu vaccine policy, since effectiveness is questionable) and use the factories to make Ebola vaccine.

Influenza kills perhaps 2/10,000, but there is no evidence the elderly people who die from flu even benefit from flu vaccinations. Ebola kills 2/3.  Do the math, DHHS!

DHHS wasted most of the 70 billion dollars it spent on biodefense and pandemic preparedness since 9/11/2001. The United States has no stockpile of the recommended gear, no early diagnostic test, no vaccine and no drug for Ebola even though Ebola was put into the highest threat category (Category A, Tier 1):  "the HHS Secretary has determined that the biological agents and toxins listed in this section have the potential to pose a severe threat to public health and safety..."

DHHS could redeem itself by by taking some of its allotment and spending it on what Americans truly need and want. Why do Americans pay the salary of an Assistant DHHS Secretary for Preparedness  and Response?  Dr. Nicole Lurie, please get off your Rear, Admiral (in the Public Health Service) and start making Ebola vaccines with those $440 million manufacturing facilities we paid for!

Hospitals are not ready, and cannot become ready: Ebola requires new healthcare facilities. Ebola is a huge money-loser; will hospitals take these patients?/ AP

On Sept 30 I wrote a blog post about how CDC's Director Frieden was wrong to claim that any US hospital could manage an Ebola patient.  Circumstances sadly proved me right in the case of Dallas, Texas.  Has that changed now that we have had more time to prepare?

After the death of Thomas Eric Duncan, every Ebola patient in the US was treated in one of 4 specialized US bio-containment ICU-level facilities, and survived.  Then Dr. Spencer developed Ebola, and he was placed in NYC's Bellevue Hospital, in an Ebola-designated isolation ward.  As best we know, he has done well.  Does this mean US hospitals have gotten up to speed on Ebola?

No.  Most people are not aware that both Mr. Duncan and Dr. Spencer were treated in ICUs where they were the only patient.  Everyone else was moved out. Bellevue had to transfer patients to another hospital to free up the many staff needed to care for him.  Nurse Pham had 25 health care providers working on her alone, at NIH.  The WSJ noted that building an appropriate isolation room, comparable to a hospital within a hospital, cost Bellevue $3-4 million dollars per patient room.

Last night, the Associated Press did an in-depth story about the Ebola preparedness of US hospitals. It echoed my concerns.  Specifically:

• 75% of ER and Infectious Disease docs felt their facilities were not prepared for Ebola
• the average number of protective suits with powered air-purifying respirators (PAPRs) per hospital is ten
• Despite hundreds of millions of dollars spent on Ebola research, there are no countermeasures
• As of last week, there "were no [federal] emergency stockpiles of the waterproof gowns, surgical hoods, full face shields, boot covers or other gear that the CDC recommends for treating Ebola patients." 
• "Among isolation care doctors and nurses, 14 percent said they'd call in sick, and one in four critical care and emergency staff said the same. Among the isolation care staff, 17 percent said they wouldn't work near Ebola patients; half of critical care and emergency staff said the same.
• Adalja, a member of the Public Health Committee of the Infectious Disease Society of America, called the survey findings troubling and contended they show that many medical staffers "are not confident in the infection control procedures at their hospital.'"

Both the AP story, and the head of Johns' Hopkins Emergency Services, note the need for more bio-containment units, where patients can be safely treated without exposing healthcare workers or other patients to Ebola.  But bio-containment units will be insufficient if the US has hundreds or thousands of Ebola patient, as the number of patients will exceed the entire country's ability to safely and effectively provide them the very complex care that is needed to pull them through.  Right now there are 19 bio-containment beds for the entire US.

Ebola causes a clinical illness characterized by cytokine storm, capillary leak syndrome, disseminated intravascular coagulation, and multiorgan failure.  This is why some patients have needed dialysis and ventilation.  Dr. Bruce Ribner, who cared for several Ebola patients at Emory, notes:

"The general dogma in our industry in July was that if patients got so ill that they required dialysis or ventilator support there was no purpose in doing those interventions because they would invariably die," Ribner said."I think we have changed the algorithm for how aggressive we can be in caring for patients with Ebola virus."

Even with the best of care at US hospitals, patients with these syndromes have an approximately 50% survival rate.  It is unlikely that the US healthcare system will be able to duplicate the current  89% survival rate, once the number of Ebola patients needing care increases.  And the dogma could revert to one of not performing such aggressive measures, which place healthcare workers at the most risk, once case numbers rise.  

Emerging targets and novel approaches to Ebola virus prophylaxis and treatment.

This article discusses literally a couple dozen vaccines and drugs that are in development for Ebola.  How is their testing being fast-tracked ?

BioDrugs. 2013 Dec;27(6):565-83. doi: 10.1007/s40259-013-0046-1.
Choi JH1, Croyle MA.

Author information

Abstract

Ebola is a highly virulent pathogen causing severe hemorrhagic fever with a high case fatality rate in humans and non-human primates (NHPs). Although safe and effective vaccines or other medicinal agents to block Ebola infection are currently unavailable, a significant effort has been put forth to identify several promising candidates for the treatment and prevention of Ebola hemorrhagic fever. Among these, recombinant adenovirus-based vectors have been identified as potent vaccine candidates, with some affording both pre- and post-exposure protection from the virus. Recently, Investigational New Drug (IND) applications have been approved by the US Food and Drug Administration (FDA) and phase I clinical trials have been initiated for two small-molecule therapeutics: anti-sense phosphorodiamidate morpholino oligomers (PMOs: AVI-6002, AVI-6003) and lipid nanoparticle/small interfering RNA (LNP/siRNA: TKM-Ebola). These potential alternatives to vector-based vaccines require multiple doses to achieve therapeutic efficacy, which is not ideal with regard to patient compliance and outbreak scenarios. These concerns have fueled a quest for even better vaccination and treatment strategies. Here, we summarize recent advances in vaccines or post-exposure therapeutics for prevention of Ebola hemorrhagic fever. The utility of novel pharmaceutical approaches to refine and overcome barriers associated with the most promising therapeutic platforms are also discussed.

The survival of filoviruses (Ebola and Marburg) in liquids, on solid substrates and in a dynamic aerosol (Thx Washington's Blog)

J Appl Microbiol. 2010 Nov;109(5):1531-9.

The survival of filoviruses (Ebola and Marburg) in liquids, on solid substrates and in a dynamic aerosol

Piercy TJ1, Smither SJ, Steward JA, Eastaugh L, Lever MS.

Author information

Abstract

AIMS:

Filoviruses are associated with high morbidity and lethality rates in humans, are capable of human-to-human transmission, via infected material such as blood, and are believed to have low infectious doses for humans. Filoviruses are able to infect via the respiratory route and are lethal at very low doses in experimental animal models, but there is minimal information on how well the filoviruses survive within aerosol particles. There is also little known about how well filoviruses survive in liquids or on solid surfaces which is important in management of patients or samples that have been exposed to filoviruses.

METHODS AND RESULTS:

Filoviruses were tested for their ability to survive in different liquids and on different solid substrates at different temperatures. The decay rates of filoviruses in a dynamic aerosol were also determined.

CONCLUSIONS:

Our study has shown that Lake Victoria marburgvirus (MARV) and Zaire ebolavirus (ZEBOV) can survive for long periods in different liquid media and can also be recovered from plastic and glass surfaces at low temperatures for over 3 weeks. The decay rates of ZEBOV and Reston ebolavirus (REBOV) plus MARV within a dynamic aerosol were calculated. ZEBOV and MARV had similar decay rates, whilst REBOV showed significantly better survival within an aerosol.

SIGNIFICANCE AND IMPACT OF THE STUDY:

Data on the survival of two ebolaviruses are presented for the first time. Extended data on the survival of MARV are presented. Data from this study extend the knowledge on the survival of filoviruses under different conditions and provide a basis with which to inform risk assessments and manage exposure to filoviruses.

CDC now admits Ebola can float through the air, and land on doorknobs/ CDC

CDC issued a new poster Friday night October 24, which admits Ebola may in fact be airborne.

But CDC says it doesn't travel farther than 3 feet.  Well, at least CDC is starting to move the narrative.  Maybe tomorrow it will be 5 feet.  Then 10.  Maybe next month they will tell us why all the victims' possessions are being incinerated and apartments fumigated.  (This article could explain it.)

Just remember: historically, Ebola spread fast in healthcare facilities.  Even CDC agrees: "EVD (Ebola Virus Disease) is highly transmissible in healthcare setting especially with severely ill patients and patients who have died. "

UPDATE Oct. 28: Thanks to Washington's Blog for this piece about a study showing that particles expelled during coughing may travel 20 feet.  And see this piece, which I published on my blog earlier, that reviews in great detail the subject of spread by airborne droplet nuclei.  Finally, I just discovered this 4 week old piece from Washington's blog quoting many experts on aerosol transmissibility.

UPDATE Oct 28:  Today's NY Times acknowledges you can potentially get Ebola from a toilet (or bathroom).

UPDATE Oct 30:  CDC has removed the poster!  The NY Post wrote before and after stories about the poster.

UPDATE Oct 31:  Huffington Post discusses CDC's new method of splitting aerosol hairs.

UPDATE Oct 31:  There is a new CDC poster, which extends the range for infectious droplet nuclei to 6 feet, but continues to be somewhat ambiguous.  (Hey, didn't I predict CDC was going to extend the droplet distance?) (I have updated the link to a screen shot as this 2nd poster was taken down, too.)

UPDATE Nov 2:  CDC changed the poster again!  They removed the one that said droplets can spread 6 feet. The doorknob is gone.  The 3d version attempts to distinguish between spread by large droplets and airborne spread, failing to acknowledge that droplets vary in size and in ability to remain airborne, while Ebola virus may remain viable for prolonged periods (hours, days and even weeks) under ideal conditions. Here is the real deal on droplets.

5 Ebola patients in Kikwit outbreak had no physical contact to explain transmission, and scientists suggest other mechanisms

The following paper was written by CDC scientists in 1999.

J Infect Dis. 1999 Feb;179 Suppl 1:S92-7. 

Ebola Hemorrhagic Fever, Kikwit, Democratic Republic of the Congo, 1995: risk factors for patients without a reported exposure. 

Roels TH1, Bloom AS, Buffington J, Muhungu GL, Mac Kenzie WR, Khan AS, Ndambi R, Noah DL, Rolka HR, Peters CJ, Ksiazek TG.

Author information

Abstract

In 1995, 316 people became ill with Ebola hemorrhagic fever (EHF) in Kikwit, Democratic Republic of the Congo. The exposure source was not reported for 55 patients (17%) at the start of this investigation, and it remained unknown for 12 patients after extensive epidemiologic evaluation. Both admission to a hospital and visiting a person with fever and bleeding were risk factors associated with infection. Nineteen patients appeared to have been exposed while visiting someone with suspected EHF, although they did not provide care. Fourteen of the 19 reported touching the patient with suspected EHF; 5 reported that they had no physical contact. Although close contact while caring for an infected person was probably the major route of transmission in this and previous EHF outbreaks, the virus may have been transmitted by touch, droplet, airborne particle, or fomite; thus, expansion of the use of barrier techniques to include casual contacts might prevent or mitigate future epidemics.

Here is the free full text, from which the next 2 paragraphs were extracted:

Of the 23 patients in our study who were subsequently determined to have had previous exposure to a case of EHF, 19 had merely visited another patient with EHF and were not involved in patient care. None reportedly had any contact with patient blood, feces, vomitus, urine, or saliva, although 14 reported touching a patient with EHF. Recent immunohistochemical examination of skin biopsy specimens from patients with EHF has demonstrated viral antigens in skin and sweat glands [16], supporting the hypothesis that EHF may have been transmitted to these individuals in Kikwit (and others in previous outbreaks) by brief, unnoticed, superficial contact with EHF-in-fected persons.
The transmission mode in the 5 patients who became infected without any physical contact remains enigmatic. However, animal experiments have documented transmission of EBO virus via noncontact routes. For example, both guinea pigs and monkeys have been infected experimentally with EBO virus by direct installation of drops into the eye and throat [17]. Transmission of EBO virus from experimentally infected monkeys to control monkeys in separate cages has also been documented [18]. Furthermore, airborne spread was suggested during the EBO epizootic outbreak in Reston, Virginia [19, 20, 21]. In a review, Peters et al. [22] concluded that although the major mode of interhuman transmission of hemorrhagic fevers is direct contact, transmission via large droplets, aerosolized particles, or fomites cannot be excluded. This may explain the mode of transmission in the 5 patients without reported physical contact

NY/NJ/IL impose health care worker quarantine after NYC doctor and unidentified heallthcare worker at Newark Airport hospitalized for potential Ebola/ WaPo

A quarantine will help stop cases appearing in the US in the near-term, but may mean that fewer medical professionals will volunteer to work in Africa, making control of Africa's epidemic harder, thus making things worse for the US in the long-term.  (Only 0.5% of MSF staff or less have developed Ebola.) From today's WaPO:

...A health-care worker who flew into Newark Liberty International Airport on Friday and had no symptoms at the time would still be quarantined because she had treated Ebola patients in West Africa, Christie said.

The New Jersey Department of Health announced Friday evening that the unidentified woman had “developed a fever and is now in isolation and being evaluated at University Hospital in Newark...”

Finally, today's WaPo includes an article that instead of trying to assuage panic or imply Ebola may come from Russia, is telling the truth:  Michael Gerson's The World is In Denial About Ebola's True Threat.
Oh, and can someone explain why BioRecovery Corp is cleaning out Dr. Spencer's apartment if Ebola can only be transmitted by direct contact with bodily fluids?  And why Nurses Pham and Vinson had their property carted away and incinerated? 

Look, CDC is simply lying. Its own publications acknowledge that Ebola may aerosolize, and must be contained in BSL-4 facilities (that are not currently available in any ordinary hospitals) / CDC

Ebola is a designated BSL-4 (Biosafety Level 4) virus.  It requires the maximal level of containment possible.  [Anthrax, by the way, is less dangerous, requiring less containment (BSL-3) than Ebola.]  Ebola's mortality rate is the highest I know of, for any infectious disease.

CDC acknowledges (below, in a 2009 publication on page 45) that Ebola requires BSL-4 containment because it "pose[s] a high individual risk of aerosol-transmitted laboratory infections and life-threatening disease that is frequently fatal, for which there are no vaccines or treatments..."

http://www.cdc.gov/biosafety/publications/bmbl5/bmbl.pdf

Biosafety Level 4 is required for work with dangerous and exotic agents that pose a high individual risk of aerosol-transmitted laboratory infections and life-threatening disease that is frequently fatal, for which there are no vaccines or treatments, or a related agent with unknown risk of transmission. Agents with a close or identical antigenic relationship to agents requiring BSL-4 containment must be handled at this level until sufficient data are obtained either to confirm continued work at this level, or re-designate the level. Laboratory staff must have specific and thorough training in handling extremely hazardous infectious agents. Laboratory staff must understand the primary and secondary containment functions of standard and special practices, containment equipment, and laboratory design characteristics.  

All laboratory staff and supervisors must be competent in handling agents and procedures requiring BSL-4 containment. The laboratory supervisor in accordance with institutional policies controls access to the laboratory.

There are two models for BSL-4 laboratories: (Neither exists in regular hospitals--Nass)
1. A Cabinet Laboratory—Manipulation of agents must be performed in a Class III BSC; and

2. A Suit Laboratory—Personnel must wear a positive pressure supplied air protective suit.BSL-4 cabinet and suit laboratories have special engineering and design features to prevent microorganisms from being disseminated into the environment.

And for those needing additional confirmation, on page 251 of this same CDC publication, CDC lists the required level of bio-containment for each known arbovirus and hemorrhagic fever virus.  Ebola is among a small group that requires BioSafety Level 4.

The Federation of American Scientists describes how a BSL-4 facility is designed and functions:

BSL-4, Biosafety Level 4

Required for work with dangerous and exotic agents which pose a high individual risk of life-threatening disease. The facility is either in a separate building or in a controlled area within a building, which is completely isolated from all other areas of the building. Walls, floors, and ceilings of the facility are constructed to form a sealed internal shell which facilitates fumigation and is animal and insect proof. A dedicated non-recirculating ventilation system is provided. The supply and exhaust components of the system are balanced to assure directional airflow from the area of least hazard to the area(s) of greatest potential hazard. Within work areas of the facility, all activities are confined to Class III biological safety cabinets, or Class II biological safety cabinets used with one-piece positive pressure personnel suits ventilated by a life support system. The Biosafety Level 4 laboratory has special engineering and design features to prevent microorganisms from being disseminated into the environment. Personnel enter and leave the facility only through the clothing change and shower rooms, and shower each time they leave the facility. Personal clothing is removed in the outer clothing change room and kept there. A specially designed suit area may be provided in the facility to provide personnel protection equivalent to that provided by Class III cabinets. The exhaust air from the suit area is filtered by two sets of HEPA filters installed in series. Supplies and materials needed in the facility are brought in by way of double-doored autoclave, fumigation chamber, or airlock, which is appropriately decontaminated between each use. Viruses assigned to Biosafety Level 4 include Crimean-Congo hemorrhagic fever, Ebola, Junin, Lassa fever, Machupo, Marburg, and tick-borne encephalitis virus complex (including Absettarov, Hanzalova, Hypr, Kumlinge, Kyasanur Forest disease, Omsk hemorrhagic fever, and Russian Spring-Summer encephalitis). 

BTW, since BSL-4 agents are considered potential biowarfare threats, BSL-4 labs (such as that at Rocky Mountain Laboratory in Hamilton, Montana) require an iris scan for entry and have armed guards, to prevent theft of microorganisms.  Will Bellevue Hospital add these features? 

I should have earlier linked to this excellent piece by David Willman (LA Times) that explores potential aerosol transmission, the problems identifying when people become infectious, and the limitations of airport screening.

Ebola Causes Chronic Illnesses in Those Who Manage to Recover/ CBS and USAMRIID

From CBS:

But unfortunately, Ebola survivors do often develop certain chronic inflammatory conditions that affect the joints and eyes, problems that can follow a survivor through the remainder of their life. Dr. Amar Safdar, associate professor of infectious diseases and immunology at NYU Langone Medical Center, told CBS News these chronic conditions are a result of the body's immune response.

He said Ebola survivors are at risk for arthralgia, a type of joint and bone pain that can feel similar to arthritis. Ebola survivors also frequently report complications with eyes and vision, an inflammatory condition known as uveitis which can cause excess tearing, eye sensitivity, eye inflammation and even blindness.

 "No one knows exactly why," Safdar told CBS News. "Certain infections or certain viruses have been known to cause uveitis. It is treated with giving steroids and primarily something that will dilate the pupil."

As acknowledged by scientists at USAMRIID:  

Moreover, the quality of life of patients following infection and treatment may require additional development efforts or the combination of multiple therapeutic approaches. As seen in outbreaks, the clinical sequelae observed in patients that survive infection are severe and life changing. These observations emphasize the need for medical countermeasures that not only provide survival but also decrease morbidity and long-term pathological outcomes following infection.

UPDATE Nov 3:  ABC reporting from Sierra Leone: 

“We are seeing a lot of people with vision problems,” Dr. Margaret Nanyonga, a psycho-social support officer for WHO, said at a conference in Sierra Leone last week. “Some complain of clouded vision, but for others the visual loss is progressive. I have seen two people who are now blind.”

Approximately 50 percent of Ebola survivors she has treated in Kenema, Sierra Leone’s third-largest city, report declining health after fighting off the deadly virus, Nanyonga said. Besides deteriorating vision, they are complaining of body aches, chest pain, headaches and fatigue. This is consistent with symptoms experienced by survivors in previous outbreaks, she said.

...There are very few scientific reports looking at the ongoing health problems of those who are cured of Ebola. In one small study, a majority of 29 people who survived a 1995 outbreak in the Democratic Republic of Congo reported a significant amount of joint pain, muscle aches and fatigue. They were still experiencing deteriorating health up to a year and a half after recovery, the researchers found. 

UPDATE Nov 9: According to the American Association of Blood Banks:

"Convalescence may be protracted and accompanied by arthralgia, orchitis, recurrent hepatitis, transverse myelitis, psychosocial disturbances or uveitis." 

Indemnifying Pharma for Ebola Vaccines: Recipe for Problems?

When did pharmaceutical manufacturers demand to be indemnified by governments, when previously asked to produce vaccines?

First time:  1976 swine flu.  One soldier died of swine flu at Fort Dix, the virus never did spread through the US population, but 45 million Americans were vaccinated with an unecessary vaccine, several hundred developed Guillain Barre syndrome (GBS), and about 30 died from GBS.

Second time:  2009 Swine flu.  This H1N1 influenza A pandemic turned out to be no more dangerous than usual yearly flu A.  But adjuvanted Glaxo vaccine Pandemrix caused about 800 cases of narcolepsy in children, and additional cases in adults.

Now they want to be indemnified for Ebola vaccines.  What do the vaccine companies know about the risk, this time?  Once they gain indemnification. as they surely will, there is no incentive for them to make the safest vaccines.

Airborne Spread of Ebola from Pigs to Macaques/ Nature

Not sure why this is still a subject for debate.  Animal models establish that Ebola can be transmitted via aerosol secretions under lab conditions.  The question remaining is how often this happens in humans. Maybe it does; maybe it doesn't.

Despite CDC protestations regarding airborne spread, the new guidelines for personal protective equipment issued by CDC on Oct 20 demonstrate that CDC is as concerned as I am about aerosolized droplet spread of Ebola. These measures include:

• Respirators, including either N95 respirators or powered air purifying respirator(PAPR)
• Single-use, full-face shield that is disposable
• Surgical hoods to ensure complete coverage of the head and neck

Here is the Nature article that got a lot of attention, in which pigs spread Ebola to macaques in a nearby cage via aerosols.  Here is a pdf of the article.

Transmission of Ebola virus from pigs to non-human primates
Hana M. Weingartl, Carissa Embury-Hyatt, Charles Nfon, Anders Leung, Greg Smith, Gary Kobinger    15 November 2012

Ebola viruses (EBOV) cause often fatal hemorrhagic fever in several species of simian primates including human. While fruit bats are considered natural reservoir, involvement of other species in EBOV transmission is unclear. In 2009, Reston-EBOV was the first EBOV detected in swine with indicated transmission to humans. In-contact transmission of Zaire-EBOV (ZEBOV) between pigs was demonstrated experimentally. Here we show ZEBOV transmission from pigs to cynomolgus macaques without direct contact. Interestingly, transmission between macaques in similar housing conditions was never observed. Piglets inoculated oro-nasally with ZEBOV were transferred to the room housing macaques in an open inaccessible cage system. All macaques became infected. Infectious virus was detected in oro-nasal swabs of piglets, and in blood, swabs, and tissues of macaques. This is the first report of experimental interspecies virus transmission, with the macaques also used as a human surrogate. Our finding may influence prevention and control measures during EBOV outbreaks.

And from the Discussion:

"The present study provides evidence that infected pigs can efficiently transmit ZEBOV to NHPs in conditions resembling farm setting. Our findings support the hypothesis that airborne transmission may contribute to ZEBOV spread, specifically from pigs to primates, and may need to be considered in assessing transmission from animals to humans in general. The present experimental findings would explain REBOV seropositivity of pig farmers in Philippines^2, 3 that were not involved in slaughtering or had no known contact with contaminated pig tissues." 

MSF discusses treatment approaches and its role in therapeutic drug trials

Below are excerpts from a longer discussion here. 

As one of the main providers of Ebola treatment in West Africa, MSF has chosen to take an active role in trialling experimental treatments. We add value to the trial process as we have access to large numbers of patients and therefore potential recipients of the experimental treatments. MSF will work in collaboration with organisations, academics, companies, the Ministries of Health in the affected countries and the WHO in order to implement fast-tracked clinical trials for some of the new treatments for Ebola at existing treatment sites. Experimental treatments are currently being selected and trial designs are being developed to ensure that disruption to patient care is minimal, that medical and research ethics are respected, and that sound scientific data is produced. MSF does not usually engage in research and trials for drug development, but faced with this massive outbreak, we’re taking exceptional measures...

The two most promising candidate vaccines have been identified as one developed by GlaxoSmithKline (GSK) and a second developed at the Public Health Agency of Canada in Winnipeg. There are other vaccines in development, however, and they should also be pushed through the pipeline as quickly as possible.

There are a handful of experimental treatments that also look promising, but that haven’t yet been tested for safety and efficacy in humans. The WHO has identified a number of these treatments and compiled them on a pre-selection list. As mentioned above, a number of these treatments are being selected to be tested in clinical trials. The treatments vary in type and include monoclonal antibodies, small inhibitory RNA, and antivirals... 

Excellent review of experimental vaccine and drug approaches to Ebola/ 2nd Canadian drug review

I read the full text but can't post it due to copyright.  The first review is from U Texas. 

BioDrugs. 2013 Dec;27(6):565-83. doi: 10.1007/s40259-013-0046-1.

Emerging Targets and Novel Approaches to Ebola Virus Prophylaxis and Treatment

Choi JH1, Croyle MA.

Abstract

Ebola is a highly virulent pathogen causing severe hemorrhagic fever with a high case fatality rate in humans and non-human primates (NHPs). Although safe and effective vaccines or other medicinal agents to block Ebola infection are currently unavailable, a significant effort has been put forth to identify several promising candidates for the treatment and prevention of Ebola hemorrhagic fever. Among these, recombinant adenovirus-based vectors have been identified as potent vaccine candidates, with some affording both pre- and post-exposure protection from the virus. Recently, Investigational New Drug (IND) applications have been approved by the US Food and Drug Administration (FDA) and phase I clinical trials have been initiated for two small-molecule therapeutics: anti-sense phosphorodiamidate morpholino oligomers (PMOs: AVI-6002, AVI-6003) and lipid nanoparticle/small interfering RNA (LNP/siRNA: TKM-Ebola). These potential alternatives to vector-based vaccines require multiple doses to achieve therapeutic efficacy, which is not ideal with regard to patient compliance and outbreak scenarios. These concerns have fueled a quest for even better vaccination and treatment strategies. Here, we summarize recent advances in vaccines or post-exposure therapeutics for prevention of Ebolahemorrhagic fever. The utility of novel pharmaceutical approaches to refine and overcome barriers associated with the most promising therapeutic platforms are also discussed.

From Canada's Special Pathogens Lab:

Trends Microbiol. 2014 Aug;22(8):456-63. doi: 10.1016/j.tim.2014.04.002. Epub 2014 Apr 30.

Post-Exposure Therapy of Filovirus Infections

Wong G1, Qiu X2, Olinger GG3, Kobinger GP4

Abstract

Filovirus infections cause fatal hemorrhagic fever characterized by the initial onset of general symptoms before rapid progression to severe disease; the most virulent species can cause death to susceptible hosts within 10 days after the appearance of symptoms. Before the advent of monoclonal antibody (mAb) therapy, infection of nonhuman primates (NHPs) with the most virulent filovirus species was fatal if interventions were not administered within minutes. A novel nucleoside analogue, BCX4430, has since been shown to also demonstrate protective efficacy with a delayed treatment start. This review summarizes and evaluates the potential of current experimental candidates for treating filovirus disease with regard to their feasibility and use in the clinic, and assesses the most promising strategies towards the future development of a pan-filovirus medical countermeasure.

This review from USAMRIID.  You can get the free full text here.

Viruses. 2012 Sep;4(9):1619-50. doi: 10.3390/v4091619. Epub 2012 Sep 21.

Potential vaccines and post-exposure treatments for filovirus infections

Friedrich BM1, Trefry JC, Biggins JE, Hensley LE, Honko AN, Smith DR, Olinger GG.

• 1United States Army Medical Research Institute of Infectious Diseases, Division of Virology, Frederick, MD 21702, USA. brian.m.friedrich.ctr@us.army.mil

Abstract

Viruses of the family Filoviridae represent significant health risks as emerging infectious diseases as well as potentially engineered biothreats. While many research efforts have been published offering possibilities toward the mitigation of filoviral infection, there remain no sanctioned therapeutic or vaccine strategies. Current progress in the development of filovirus therapeutics and vaccines is outlined herein with respect to their current level of testing, evaluation, and proximity toward human implementation, specifically with regard to human clinical trials, nonhuman primate studies, small animal studies, and in vitro development. Contemporary methods of supportive care and previous treatment approaches for human patients are also discussed.

CDC defined infectious respiratory droplet transmission as different than airborne

Here are CDC's definitions for the different modes of spread of infectious agents.  Scroll down to IB3b and c and you will see that CDC has defined droplet transmission as a form of contact transmission. This may be CDC's technical justification for insisting that Ebola does not spread via the airborne route, when there is ample evidence it may spread via airborne droplets.

Is This A New, More Virulent Ebola?

The West Africa Ebola mortality rate with treatment is very high. Normally, mortality drops when doctors gain experience with new diseases and learn how best to care for patients. This seems not to be the case with this Ebola.

West African Ebola may be spreading more easily than other Ebola outbreaks.  [Thanks to Washington's Blog for alerting me to Michael Osterholm's speech on C-SPAN2.]

Two very knowledgeable scientists have suggested as much.  Peter Jahrling, PhD, of NIAID (formerly USAMRIID) who has worked with Ebola for 25 years, said that the concentration of virus in patients seemed to be twice as high as in earlier epidemics.

Yes. I have a field team in Monrovia. They are running [tests]. They are telling me that viral loads are coming up very quickly and really high, higher than they are used to seeing. It turns out that in limited studies with the evacuated patients, they continued to express virus in blood and semen. What does that mean? Right now, we just don't know.

Michael Osterholm, PhD, director of the Center for Infectious Disease Research and Policy at the University of Minnesota, is a prominent public health scientist and a nationally recognized biosecurity expert.  In a speech at Johns Hopkins on October 14, he said he had just been given permission to say that Canada's Gary Kobinger found that the pathological lesions in the lungs from macaques infected with west African Ebola were "much much more severe" than expected. "It was unlike any of the [earlier] ebola viruses they have seen in monkeys." [at 20 minutes]

He warned the audience to expect the unexpected as the epidemic continues: "Do not expect that anything carved in stone today won't be blown up by some stick of dynamite."

... In other comments, Osterholm said an international Ebola research agenda is urgently needed to answer a number of questions. For example, more virus isolates are needed for genetic studies, and information on clinical virology is sorely lacking. 

Government experts and the media tell us that Ebola can only be spread by direct contact, and is easily killed with diluted bleach.  Why, then, have virtually all the belongings of nurses Nina Pham and Amber Vinson been removed from their apartments?  Everything removed has been burned.

From San Antonio Eyewitness News:

... TCEQ photos of nurse Nina Pham's home after decontamination tell the story. The apartment looks practically back to the way it was before she moved in. The refrigerator and cabinets are empty, and only a few large items remain. They are proof of her life before the virus, and another symbol of how Ebola has turned it upside down.

In all, the TCEQ said it filled 53 barrels with Vinson's belongings, 21 from Pham and five from the City of Dallas. All were driven to a Port Arthur Texas facility, where they were incinerated.

Extreme Abundance of Caution Versus Extreme Abundance of Hubris in Ebola Scare

From NBC news today:  

A helicopter landed aboard a cruise ship Saturday to pick up a blood sample from a passenger who may have handled fluids from an Ebola patient, ahead of the Carnival Magic’s planned docking at Galveston, Texas, Sunday.

Carnival said Texas health officials requested that a sample be taken from the passenger and tested, but that the ship is still scheduled to arrive Sunday morning. The company said of the passenger, who is in quarantine, that “she’s feeling absolutely fine."

Absolutely fine. Really?  Why isn't everyone else who came into contact with an Ebola patient being tracked down and asked for blood samples?  Why was her cruise ship prevented from offloading her in Belize, and failed to stop as scheduled in Cozumel, Mexico?

Instead of telling us this is due solely to "an extreme abundance of caution" why not simply tell the truth and regain some credibility on this issue?

On October 16, the New Jersey Health Department said it expects all NJ hospitals to be able to handle an Ebola case.  Well, I hope this uninformed hubris does not come back to bite NJ healthcare workers, who intelligently suggested that cases go to biocontainment facilities, instead.