Category: Virus

Infectious disease specialists from University of Illinois make first recommendation that health workers need optimal respiratory protection for Ebola, due to possible transmission in the air.

On By A.P.In Ebola, Kebmodee, Medicine, ScienceLeave a comment

Lisa M Brosseau, ScD, and Rachael Jones, PhD

The authors are national experts on respiratory protection and infectious disease transmission. In May they published a similar commentary on MERS-CoV. Dr Brosseau is a Professor and Dr Jones an Assistant Professor in the School of Public Health, Division of Environmental and Occupational Health Sciences, at the University of Illinois at Chicago.

Healthcare workers play a very important role in the successful containment of outbreaks of infectious diseases like Ebola. The correct type and level of personal protective equipment (PPE) ensures that healthcare workers remain healthy throughout an outbreak—and with the current rapidly expanding Ebola outbreak in West Africa, it’s imperative to favor more conservative measures.

The precautionary principle—that any action designed to reduce risk should not await scientific certainty—compels the use of respiratory protection for a pathogen like Ebola virus that has:

•No proven pre- or post-exposure treatment modalities
•A high case-fatality rate
•Unclear modes of transmission

We believe there is scientific and epidemiologic evidence that Ebola virus has the potential to be transmitted via infectious aerosol particles both near and at a distance from infected patients, which means that healthcare workers should be wearing respirators, not facemasks (1).

The minimum level of protection in high-risk settings should be a respirator with an assigned protection factor greater than 10. A powered air-purifying respirator (PAPR) with a hood or helmet offers many advantages over an N95 filtering facepiece or similar respirator, being more protective, comfortable, and cost-effective in the long run.

We strongly urge the US Centers for Disease Control and Prevention (CDC) and the World Health Organization (WHO) to seek funds for the purchase and transport of PAPRs to all healthcare workers currently fighting the battle against Ebola throughout Africa—and beyond.

There has been a lot of on-line and published controversy about whether Ebola virus can be transmitted via aerosols. Most scientific and medical personnel, along with public health organizations, have been unequivocal in their statements that Ebola can be transmitted only by direct contact with virus-laden fluids (2,3) and that the only modes of transmission we should be concerned with are those termed “droplet” and “contact.”

These statements are based on two lines of reasoning. The first is that no one located at a distance from an infected individual has contracted the disease, or the converse, every person infected has had (or must have had) “direct” contact with the body fluids of an infected person.

This reflects an incorrect and outmoded understanding of infectious aerosols, which has been institutionalized in policies, language, culture, and approaches to infection control. We will address this below. Briefly, however, the important points are that virus-laden bodily fluids may be aerosolized and inhaled while a person is in proximity to an infectious person and that a wide range of particle sizes can be inhaled and deposited throughout the respiratory tract.

The second line of reasoning is that respirators or other control measures for infectious aerosols cannot be recommended in developing countries because the resources, time, and/or understanding for such measures are lacking (4).

Although there are some important barriers to the use of respirators, especially PAPRs, in developing countries, healthcare workers everywhere deserve and should be afforded the same best-practice types of protection, regardless of costs and resources. Every healthcare worker is a precious commodity whose well-being ensures everyone is protected.

If we are willing to offer infected US healthcare workers expensive treatments and experimental drugs free of charge when most of the world has no access to them, we wonder why we are unwilling to find the resources to provide appropriate levels of comparatively less expensive respiratory protection to every healthcare worker around the world.

How are infectious diseases transmitted via aerosols?

Medical and infection control professionals have relied for years on a paradigm for aerosol transmission of infectious diseases based on very outmoded research and an overly simplistic interpretation of the data. In the 1940s and 50s, William F. Wells and other “aerobiologists” employed now significantly out-of-date sampling methods (eg, settling plates) and very blunt analytic approaches (eg, cell culturing) to understand the movement of bacterial aerosols in healthcare and other settings. Their work, though groundbreaking at the time, provides a very incomplete picture.

Early aerobiologists were not able to measure small particles near an infectious person and thus assumed such particles existed only far from the source. They concluded that organisms capable of aerosol transmission (termed “airborne”) can only do so at around 3 feet or more from the source. Because they thought that only larger particles would be present near the source, they believed people would be exposed only via large “droplets” on their face, eyes, or nose.

Modern research, using more sensitive instruments and analytic methods, has shown that aerosols emitted from the respiratory tract contain a wide distribution of particle sizes—including many that are small enough to be inhaled (5,6). Thus, both small and large particles will be present near an infectious person.

The chance of large droplets reaching the facial mucous membranes is quite small, as the nasal openings are small and shielded by their external and internal structure. Although close contact may permit large-droplet exposure, it also maximizes the possibility of aerosol inhalation.

As noted by early aerobiologists, liquid in a spray aerosol, such as that generated during coughing or sneezing, will quickly evaporate (7), which increases the concentration of small particles in the aerosol. Because evaporation occurs in milliseconds, many of these particles are likely to be found near the infectious person.

The current paradigm also assumes that only “small” particles (less than 5 micrometers [mcm]) can be inhaled and deposited in the respiratory tract. This is not true. Particles as large as 100 mcm (and perhaps even larger) can be inhaled into the mouth and nose. Larger particles are deposited in the nasal passages, pharynx, and upper regions of the lungs, while smaller particles are more likely to deposit in the lower, alveolar regions. And for many pathogens, infection is possible regardless of the particle size or deposition site.

It’s time to abandon the old paradigm of three mutually exclusive transmission routes for a new one that considers the full range of particle sizes both near and far from a source. In addition, we need to factor in other important features of infectivity, such as the ability of a pathogen to remain viable in air at room temperature and humidity and the likelihood that systemic disease can result from deposition of infectious particles in the respiratory system or their transfer to the gastrointestinal tract.

We recommend using “aerosol transmissible” rather than the outmoded terms “droplet” or “airborne” to describe pathogens that can transmit disease via infectious particles suspended in air.

Is Ebola an aerosol-transmissible disease?

We recently published a commentary on the CIDRAP site discussing whether Middle East respiratory syndrome (MERS) could be an aerosol-transmissible disease, especially in healthcare settings. We drew comparisons with a similar and more well-studied disease, severe acute respiratory syndrome (SARS).

For Ebola and other filoviruses, however, there is much less information and research on disease transmission and survival, especially in healthcare settings.

Being at first skeptical that Ebola virus could be an aerosol-transmissible disease, we are now persuaded by a review of experimental and epidemiologic data that this might be an important feature of disease transmission, particularly in healthcare settings.

What do we know about Ebola transmission?

No one knows for certain how Ebola virus is transmitted from one person to the next. The virus has been found in the saliva, stool, breast milk, semen, and blood of infected persons (8,9). Studies of transmission in Ebola virus outbreaks have identified activities like caring for an infected person, sharing a bed, funeral activities, and contact with blood or other body fluids to be key risk factors for transmission (10-12).

On the basis of epidemiologic evidence, it has been presumed that Ebola viruses are transmitted by contaminated hands in contact with the mouth or eyes or broken skin or by splashes or sprays of body fluids into these areas. Ebola viruses appear to be capable of initiating infection in a variety of human cell types (13,14), but the primary portal or portals of entry into susceptible hosts have not been identified.

Some pathogens are limited in the cell type and location they infect. Influenza, for example, is generally restricted to respiratory epithelial cells, which explains why flu is primarily a respiratory infection and is most likely aerosol transmissible. HIV infects T-helper cells in the lymphoid tissues and is primarily a bloodborne pathogen with low probability for transmission via aerosols.

Ebola virus, on the other hand, is a broader-acting and more non-specific pathogen that can impede the proper functioning of macrophages and dendritic cells—immune response cells located throughout the epithelium (15,16). Epithelial tissues are found throughout the body, including in the respiratory tract. Ebola prevents these cells from carrying out their antiviral functions but does not interfere with the initial inflammatory response, which attracts additional cells to the infection site. The latter contribute to further dissemination of the virus and similar adverse consequences far beyond the initial infection site.

The potential for transmission via inhalation of aerosols, therefore, cannot be ruled out by the observed risk factors or our knowledge of the infection process. Many body fluids, such as vomit, diarrhea, blood, and saliva, are capable of creating inhalable aerosol particles in the immediate vicinity of an infected person. Cough was identified among some cases in a 1995 outbreak in Kikwit, Democratic Republic of the Congo (11), and coughs are known to emit viruses in respirable particles (17). The act of vomiting produces an aerosol and has been implicated in airborne transmission of gastrointestinal viruses (18,19). Regarding diarrhea, even when contained by toilets, toilet flushing emits a pathogen-laden aerosol that disperses in the air (20-22).

Experimental work has shown that Marburg and Ebola viruses can be isolated from sera and tissue culture medium at room temperature for up to 46 days, but at room temperature no virus was recovered from glass, metal, or plastic surfaces (23). Aerosolized (1-3 mcm) Marburg, Ebola, and Reston viruses, at 50% to 55% relative humidity and 72°F, had biological decay rates of 3.04%, 3.06%. and 1.55% per minute, respectively. These rates indicate that 99% loss in aerosol infectivity would occur in 93, 104, and 162 minutes, respectively (23).

In still air, 3-mcm particles can take up to an hour to settle. With air currents, these and smaller particles can be transported considerable distances before they are deposited on a surface.

There is also some experimental evidence that Ebola and other filoviruses can be transmitted by the aerosol route. Jaax et al (24) reported the unexpected death of two rhesus monkeys housed approximately 3 meters from monkeys infected with Ebola virus, concluding that respiratory or eye exposure to aerosols was the only possible explanation.

Zaire Ebola viruses have also been transmitted in the absence of direct contact among pigs (25) and from pigs to non-human primates (26), which experienced lung involvement in infection. Persons with no known direct contact with Ebola virus disease patients or their bodily fluids have become infected (12).

Direct injection and exposure via a skin break or mucous membranes are the most efficient ways for Ebola to transmit. It may be that inhalation is a less efficient route of transmission for Ebola and other filoviruses, as lung involvement has not been reported in all non-human primate studies of Ebola aerosol infectivity (27). However, the respiratory and gastrointestinal systems are not complete barriers to Ebola virus. Experimental studies have demonstrated that it is possible to infect non-human primates and other mammals with filovirus aerosols (25-27).

Altogether, these epidemiologic and experimental data offer enough evidence to suggest that Ebola and other filoviruses may be opportunistic with respect to aerosol transmission(28). That is, other routes of entry may be more important and probable, but, given the right conditions, it is possible that transmission could also occur via aerosols.

Guidance from the CDC and WHO recommends the use of facemasks for healthcare workers providing routine care to patients with Ebola virus disease and respirators when aerosol-generating procedures are performed. (Interestingly, the 1998 WHO and CDC infection-control guidance for viral hemorrhagic fevers in Africa, still available on the CDC Web site, recommends the use of respirators.)

Facemasks, however, do not offer protection against inhalation of small infectious aerosols, because they lack adequate filters and do not fit tightly against the face (1). Therefore, a higher level of protection is necessary.

Which respirator to wear?

As described in our earlier CIDRAP commentary, we can use a Canadian control-banding approach to select the most appropriate respirator for exposures to Ebola in healthcare settings (29). (See this document for a detailed description of the Canadian control banding approach and the data used to select respirators in our examples below.)

The control banding method involves the following steps:

1.Identify the organism’s risk group (1 to 4). Risk group reflects the toxicity of an organism, including the degree and type of disease and whether treatments are available. Ebola is in risk group 4, the most toxic organisms, because it can cause serious human or animal disease, is easily transmitted, directly or indirectly, and currently has no effective treatments or preventive measures.

2.Identify the generation rate. The rate of aerosol generation reflects the number of particles created per time (eg, particles per second). Some processes, such as coughing, create more aerosols than others, like normal breathing. Some processes, like intubation and toilet flushing, can rapidly generate very large quantities of aerosols. The control banding approach assigns a qualitative rank ranging from low (1) to high (4) (eg, normal breathing without coughing has a rank of 1).

3.Identify the level of control. Removing contaminated air and replacing it with clean air, as accomplished with a ventilation system, is effective for lowering the overall concentration of infectious aerosol particles in a space, although it may not be effective at lowering concentration in the immediate vicinity of a source. The number of air changes per hour (ACH) reflects the rate of air removal and replacement. This is a useful variable, because it is relatively easy to measure and, for hospitals, reflects building code requirements for different types of rooms. Again, a qualitative ranking is used to reflect low (1) versus high (4) ACH. Even if the true ventilation rate is not known, the examples can be used to select an appropriate air exchange rate.

4.Identify the respirator assigned protection factor. Respirators are designated by their “class,” each of which has an assigned protection factor (APF) that reflects the degree of protection. The APF represents the outside, environmental concentration divided by the inside, facepiece concentration. An APF of 10 means that the outside concentration of a particular contaminant will be 10 times greater than that inside the respirator. If the concentration outside the respirator is very high, an assigned protection factor of 10 may not prevent the wearer from inhaling an infective dose of a highly toxic organism.

Practical examples

Two examples follow. These assume that infectious aerosols are generated only during vomiting, diarrhea, coughing, sneezing, or similar high-energy emissions such as some medical procedures. It is possible that Ebola virus may be shed as an aerosol in other manners not considered.

Caring for a patient in the early stages of disease (no bleeding, vomiting, diarrhea, coughing, sneezing, etc). In this case, the generation rate is 1. For any level of control (less than 3 to more than 12 ACH), the control banding wheel indicates a respirator protection level of 1 (APF of 10), which corresponds to an air purifying (negative pressure) half-facepiece respirator such as an N95 filtering facepiece respirator. This type of respirator requires fit testing.

Caring for a patient in the later stages of disease (bleeding, vomiting, diarrhea, etc). If we assume the highest generation rate (4) and a standard patient room (control level = 2, 3-6 ACH), a respirator with an APF of at least 50 is needed. In the United States, this would be equivalent to either a full-facepiece air-purifying (negative-pressure) respirator or a half-facepiece PAPR (positive pressure), but standards differ in other countries. Fit testing is required for these types of respirators.

The control level (room ventilation) can have a big effect on respirator selection. For the same patient housed in a negative-pressure airborne infection isolation room (6-12 ACH), a respirator with an assigned protection factor of 25 is required. This would correspond in the United States to a PAPR with a loose-fitting facepiece or with a helmet or hood. This type of respirator does not need fit testing.

Implications for protecting health workers in Africa

Healthcare workers have experienced very high rates of morbidity and mortality in the past and current Ebola virus outbreaks. A facemask, or surgical mask, offers no or very minimal protection from infectious aerosol particles. As our examples illustrate, for a risk group 4 organism like Ebola, the minimum level of protection should be an N95 filtering facepiece respirator.

This type of respirator, however, would only be appropriate only when the likelihood of aerosol exposure is very low. For healthcare workers caring for many patients in an epidemic situation, this type of respirator may not provide an adequate level of protection.

For a risk group 4 organism, any activity that has the potential for aerosolizing liquid body fluids, such as medical or disinfection procedures, should be avoided, if possible. Our risk assessment indicates that a PAPR with a full facepiece (APF = 50) or a hood or helmet (APF = 25) would be a better choice for patient care during epidemic conditions.

We recognize that PAPRs present some logistical and infection-control problems. Batteries require frequent charging (which requires a reliable source of electricity), and the entire ensemble requires careful handling and disinfection between uses. A PAPR is also more expensive to buy and maintain than other types of respirators.

On the other hand, a PAPR with a loose-fitting facepiece (hood or helmet) does not require fit testing. Wearing this type of respirator minimizes the need for other types of PPE, such as head coverings and goggles. And, most important, it is much more comfortable to wear than a negative-pressure respirator like an N95, especially in hot environments.

A recent report from a Medecins Sans Frontieres healthcare worker in Sierra Leone30 notes that healthcare workers cannot tolerate the required PPE for more than 40 minutes. Exiting the workplace every 40 minutes requires removal and disinfection or disposal (burning) of all PPE. A PAPR would allow much longer work periods, use less PPE, require fewer doffing episodes, generate less infectious waste, and be more protective. In the long run, we suspect this type of protection could also be less expensive.

Adequate protection is essential

To summarize, for the following reasons we believe that Ebola could be an opportunistic aerosol-transmissible disease requiring adequate respiratory protection:
•Patients and procedures generate aerosols, and Ebola virus remains viable in aerosols for up to 90 minutes.
•All sizes of aerosol particles are easily inhaled both near to and far from the patient.
•Crowding, limited air exchange, and close interactions with patients all contribute to the probability that healthcare workers will be exposed to high concentrations of very toxic infectious aerosols.
•Ebola targets immune response cells found in all epithelial tissues, including in the respiratory and gastrointestinal system.
•Experimental data support aerosols as a mode of disease transmission in non-human primates.

Risk level and working conditions suggest that a PAPR will be more protective, cost-effective, and comfortable than an N95 filtering facepiece respirator.

Acknowledgements

We thank Kathleen Harriman, PhD, MPH, RN, Chief, Vaccine Preventable Diseases Epidemiology Section, Immunization Branch, California Department of Public Health, and Nicole Vars McCullough, PhD, CIH, Manager, Global Technical Services, Personal Safety Division, 3M Company, for their input and review.

References
1.Oberg L, Brosseau LM. Surgical mask filter and fit performance. Am J Infect Control 2008 May;36(4):276-82

2.CDC. Ebola hemorrhagic fever: transmission. 2014 Aug 13

3.ECDC. Outbreak of Ebola virus disease in West Africa: third update, 1 August 2014. Stockholm: ECDC 2014 Aug 1

4.Martin-Moreno JM, Llinas G, Hernandez JM. Is respiratory protection appropriate in the Ebola response? Lancet 2014 Sep 6;384(9946):856

5.Papineni RS, Rosenthal FS. The size distribution of droplets in the exhaled breath of healthy human subjects. J Aerosol Med 1997;10(2):105-16

6.Chao CYH, Wan MP, Morawska L, et al. Characterization of expiration air jets and droplet size distributions immediately at the mouth opening. J Aerosol Sci 2009 Feb;40(2):122-33

7.Nicas M, Nazaroff WW, Hubbard A. Toward understanding the risk of secondary airborne infection: emission of respirable pathogens. J Occup Environ Hyg 2005 Mar;2(3):143-54

8.Bauchsch DG, Towner JS, Dowell SF, et al. Assessment of the risk of Ebola virus transmission from bodily fluids and fomites. J Infect Dis 2007;196:S142-7

9.Formenty P, Leroy EM, Epelboin A, et al. Detection of Ebola virus in oral fluid specimens during outbreaks of Ebola virus hemorrhagic fever in the Republic of Congo. Clin Infect Dis 2006 Jun;42(11):1521-6

10.Francesconi P, Yoti Z, Declich S, et al. Ebola hemorrhagic fever transmission and risk factors of contacts, Uganda. Emerg Infect Dis 2003 Nov;9(11):1430-7

11.Dowell SF, Mukunu R, Ksiazek TG, et al. Transmission of Ebola hemorrhagic fever: a study of risk factors in family members, Kikwit, Democratic Republic of Congo, 1995. J Infect Dis 1999 Feb;179:S87-91

12.Roels TH, Bloom AS, Buffington J, et al. Ebola hemorrhagic fever, Kikwit, Democratic Republic of the Congo, 1995: risk factors for patients without a reported exposure. J Infect Dis 1999 Feb;179:S92-7

13.Kuhl A, Hoffmann M, Muller MA, et al. Comparative analysis of Ebola virus glycoprotein interactions with human and bat cells. J Infect Dis 2011 Nov;204:S840-9

14.Hunt CL, Lennemann NJ, Maury W. Filovirus entry: a novelty in the viral fusion world. Viruses 2012 Feb;4(2):258-75

15.Bray M, Geisbert TW. Ebola virus: the role of macrophages and dendritic cells in the pathogenesis of Ebola hemorrhagic fever. Int J Biochem Cell Biol 2005 Aug;37(8):1560-6

16.Mohamadzadeh M, Chen L, Schmaljohn AL. How Ebola and Marburg viruses battle the immune system. Nat Rev Immunol 2007 Jul;7(7):556-67

17.Lindsley WG, Blachere FM, Thewlis RE, et al. Measurements of airborne influenza virus in aerosol particles from human coughs. PLoS One 2010 Nov 30;5(11):e15100

18.Caul EO. Small round structured viruses: airborne transmission and hospital control. Lancet 1994 May 21;343(8908):1240-2

19.Chadwick PR, Walker M, Rees AE. Airborne transmission of a small round structured virus. Lancet 1994 Jan 15;343(8890):171

20.Best EL, Snadoe JA, Wilcox MH. Potential for aerosolization of Clostridium difficile after flushing toilets: the role of toilet lids in reducing environmental contamination. J Hosp Infect 2012 Jan;80(1):1-5

21.Gerba CP, Wallis C, Melnick JL. Microbiological hazards of household toilets: droplet production and the fate of residual organisms. Appl Microbiol 1975 Aug;30(2):229-37

22.Barker J, Jones MV. The potential spread of infection caused by aerosol contamination of surfaces after flushing a domestic toilet. J Appl Microbiol 2005;99(2):339-47

23.Piercy TJ, Smither SJ, Steward JA, et al. The survival of filoviruses in liquids, on solid substrates and in a dynamic aerosol. J Appl Microbiol 2010 Nov;109(5):1531-9

24.Jaax N, Jahrling P, Geisbert T, et al. Transmission of Ebola virus (Zaire strain) to uninfected control monkeys in a biocontainment laboratory. Lancet 1995 Dec 23-30;346(8991-2):1669-71

25.Kobinger GP, Leung A, Neufeld J, et al. Replication, pathogenicity, shedding and transmission of Zaire ebolavirus in pigs. J Infect Dis 2011 Jul 15;204(2):200-8

26.Weingartl HM, Embury-Hyatt C, Nfon C, et al. Transmission of Ebola virus from pigs to non-human primates. Sci Rep 2012;2:811

27.Reed DS, Lackemeyer MG, Garza NL, et al. Aerosol exposure to Zaire Ebolavirus in three nonhuman primate species: differences in disease course and clinical pathology. Microb Infect 2011 Oct;13(11):930-6

28.Roy CJ, Milton DK. Airborne transmission of communicable infection—the elusive pathway. N Engl J Med 2004 Apr;350(17):1710-2

29.Canadian Standards Association. Selection, use and care of respirators. CAN/CSA Z94.4-11

30.Wolz A. Face to face with Ebola—an emergency care center in Sierra Leone. (Perspective) N Engl J Med 2014 Aug 27

http://www.cidrap.umn.edu/news-perspective/2014/09/commentary-health-workers-need-optimal-respiratory-protection-ebola

Thanks to Kebmodee for bringing this to the attention of the It’s Interesting community.

NewLink Genetics in Ames, Iowa is closing in on human trials for Ebola vaccine

On By A.P.In Ames, Ebola, ebola vaccine, Health, healthcare, Iowa, Medicine, NewLink Genetics, ScienceLeave a comment

The biotech company NewLink Genetics in Ames, Iowa is closing in on human trials for an Ebola vaccine.

“From the laboratory to moving these first human trials has moved faster than I’ve ever seen anything move before in my professional career,” said Charles Link, CEO of NewLink Genetics.

Link said they are just a few days away from human testing. During Phase 1 of testing, healthy volunteers will be given the vaccine. Researchers will test to see how safe the vaccine is and what dosage is necessary for an immune reaction.

“With a dangerous virus, you don’t ever use the dangerous virus. You basically use a little snippet of it,” said Link.

Link said that snippet is a surface protein you get from Ebola and assures us there is no Ebola is in the vaccine.

“If you get an immune reaction to the surface protein an then it sees the real Ebola, it will attack it,” said Link.

Once those tests are complete, the company will move into Phase 2 where tests focus on how effective and useful the vaccine is. Those tests will be done in West Africa.

Link said he’s hoping it’ll take less than a year, but there’s no real way of telling when the vaccine will be ready for distribution until test results start coming in.

“We want to shorten the process as much as humanely possible within the bounds of safety and the ethics that’s required to conduct these sorts of studies in healthy volunteers,” said Link.

The Phase 1 of the tests will be conducted at the National Institute of Allergy and Infectious Disease and the Walter Reed Army Medical Center.
Ames Company Close to Ebola Vaccine Trials

http://www.cbs2iowa.com/news/features/top-stories/stories/ames-company-close-ebola-vaccine-trials-30679.shtml

Could Ebola be used as an ISIS bio-weapon?

On By A.P.In EbolaLeave a comment

Ebola_Virus_Imaging_Wide

ISIS may already be thinking of using Ebola as a low-tech weapon of bio-terror, says a national security expert, who notes that the “Islamic State of Iraq and Syria” and terror groups like it wouldn’t even have to weaponize the virus to attempt to wreak strategic global infection.

Such groups could simply use human carriers to intentionally infect themselves in West Africa, then disseminate the deadly virus via the world’s air transportation system. Or so says Capt. Al Shimkus, Ret., a Professor of National Security Affairs at the U.S. Naval War College.

“The individual exposed to the Ebola Virus would be the carrier,” Shimkus told Forbes. “In the context of terrorist activity, it doesn’t take much sophistication to go to that next step to use a human being as a carrier.”

And with a significant portion of West Africa now in an open epidemic, it arguably wouldn’t be difficult for a terrorist group to simply waltz in and make off with some infected bodily fluids for use at a later time elsewhere.

They wouldn’t even have to “isolate” it, says Shimkus, who teaches a course in chemical and biological warfare. He says that if ISIS wanted to send half a dozen of its operatives into an Ebola outbreak region and intentionally expose themselves to the virus, they very well could. The idea is then once they had intentionally infected themselves, they would try to interact with as many people in their target city or country of choice.

The average fatality rate from Ebola, classified as a hemorrhagic fever, is 50 percent; but without medical treatment, that figure can range as high as 90 percent, reports the U.N. World Health Organization (WHO). The WHO also notes that although there are two potential vaccines undergoing “evaluation,” at present none are licensed.

The virus was first documented in humans in 1976 during two simultaneous outbreaks, one in Sudan and the other in the Congo, in a village near the Ebola River. The WHO reports that a type of fruit bat is thought to act as the virus’ natural host.

The virus apparently spreads into the human population via direct contact with infected animals — ranging from chimpanzees, gorillas, monkeys, forest antelope and porcupines; as well as the fruit bat itself — be they found ill or dead in the rain forest. According to the WHO, Ebola can then be spread via contact with the infected’s bodily fluids; even bedding and clothing “contaminated” with such fluids.

The idea of using human carriers to intentionally spread deadly pathogens has been around for centuries. As Shimkus points out, in the Middle Ages, adversaries threw infected corpses over their enemy’s city walls in order to spread the deadly Bubonic Plague.

If ISIS or another terrorist actor were to use Ebola in a similar manner today, Shimkus says the possibility of identifying those infected as they enter and leave the country is excellent but not 100 percent.

Even in the event of terrorists using carriers to spread Ebola in western countries like the U.S., Shimkus doesn’t think the virus would spread exponentially simply because, in theory, advanced health care systems would be equipped to identify, isolate and stop the virus.

In the May 2013 issue of the journal Global Policy, however, Amanda Teckman, author of the paper “The Bioterrorist Threat of Ebola in East Africa and Implications for Global Health and Security” concluded that “the threat of an Ebola bioterrorist attack in East Africa is a global health and security concern, and should not be ignored.”

Teckman, who holds a master’s in diplomacy and international relations at Seton Hall University, told Forbes that because ISIS’ recent beheadings are aimed at garnering attention for their self-proclaimed goal of creating an Islamic state under Sharia Law, the group is unlikely to go through the trouble of using Ebola as a weapon of terror.

“They already have our attention,” said Teckman. “But just because this is not probable for ISIS, I do believe others will at least contemplate using such suicide infectors.”

http://www.forbes.com/sites/brucedorminey/2014/10/05/ebola-as-isis-bio-weapon/

The Recovering Americans and the ‘Top Secret’ Ebola Treatment

On By A.P.In Africa, CDC, Centers for Disease Control and Prevention, Ebola, Ebola Consolidation Case Management Center, ebola vaccine, Emory University, Emory University School of Medicine, Kebmodee, Kent Brantly, Liberia, Mapp Biopharmaceuticals, Margaret Chan, Medicine, monoclonal antibody, National Institutes of Health, NIAID, NIH, Samaritan's Purse, Sanjay Gupta, Science, World Health Organization, zMappLeave a comment

Because Kent Brantly is a physician who has watched people die of Ebola, there was an especially chilling prescience to his assessment last week, between labored breaths: “I am going to die.”

His condition was grave. But then on Saturday, we saw images of Brantly’s heroic return to U.S. soil, walking with minimal assistance from an ambulance into an isolation unit at Emory University Hospital.

“One of the doctors called it ‘miraculous,'” Dr. Sanjay Gupta reported from Emory this morning, of Brantly’s turnaround within hours of receiving a treatment delivered from the U.S. National Institutes of Health. “Not a term we scientists like to throw around.”

“The outbreak is moving faster than our efforts to control it,” Dr. Margaret Chan, director of the World Health Organization, said on Friday in a plea for international help containing the virus. “If the situation continues to deteriorate, the consequences can be catastrophic in terms of lost lives, but also severe socioeconomic disruption and a high risk of spread to other countries.”

In that light, and because Ebola is notoriously incurable (and the strain at large its most lethal), it is overwhelming to hear that “Secret Serum Likely Saved Ebola Patients,” as we do this morning from Gupta’s every-20-minute CNN reports. He writes:

Three top secret, experimental vials stored at subzero temperatures were flown into Liberia last week in a last-ditch effort to save two American missionary workers [Dr. Kent Brantly and Nancy Writebol] who had contracted Ebola, according to a source familiar with details of the treatment.

Brantly had been working for the Christian aid organization Samaritan’s Purse as medical director of the Ebola Consolidation Case Management Center in Monrovia, Liberia. The group yesterday confirmed that he received a dose of an experimental serum before leaving the country.

In Gupta’s optimistic assessment, Brantly’s “near complete recovery” began within hours of receiving the treatment that “likely saved his life.” Writebol is also reportedly improved since receiving the treatment, known as zMapp. But to say that it was a secret implies a frigid American exceptionalism; that the people of West Africa are dying in droves while a classified cure lies in wait.

The “top-secret serum” is a monoclonal antibody. Administration of monoclonal antibodies is an increasingly common but time-tested approach to eradicating interlopers in the human body. In a basic monoclonal antibody paradigm, scientists infect animals (in this case mice) with a disease, the mice mount an immune response (antibodies to fight the disease), and then the scientists harvest those antibodies and give them to infected humans. It’s an especially promising area in cancer treatment.

In this case, the proprietary blend of three monoclonal antibodies known as zMapp had never been tested in humans. It had previously been tested in eight monkeys with Ebola who survived—though all received treatment within 48 hours of being infected. A monkey treated outside of that exposure window did not survive. That means very little is known about the safety and effectiveness of this treatment—so little that outside of extreme circumstances like this, it would not be legal to use. Gupta speculates that the FDA may have allowed it under the compassionate use exemption.

A small 2012 study of monoclonal antibody therapy against Ebola found that it was only effective when administered before or just after exposure to the virus. A 2013 study found that rhesus macaques given an antibody mix called MB-003 within the 48-hour window had a 43 percent chance of surviving—as opposed to their untreated counterparts, whose survival rate was zero.

This Ebola outbreak is the largest in the history of the disease, in terms of both cases and deaths, 729 887 known so far. As Chan warned in her call for urgent international action, the outbreak is geographically the largest, already in four countries with fluid population movement across porous borders and a demonstrated ability to spread by air travel. The outbreak will be stopped by strategic quarantines and preventive education, primarily proper handling of corpses. More than 60 aid workers have become infected, but many more will be needed to stem the tide.

Dr. Anthony Fauci, director of the U.S. National Institute of Allergy and Infectious Disease (NIAID), is encouraged by the antibody treatment.

“Obviously there are plans and enthusiasm to expand this,” Fauci told me. “The limiting factor is the extraordinary paucity of treatment regimens.” Right now the total amount available, to Fauci’s knowledge, is three treatment courses (in addition to what was given to Brantly and Writebol).

NIAID did some of the original research that led to the development, but this is owned by Mapp Biopharmaceuticals. “They are certainly trying to scale up,” Fauci said, “but I’ve heard that their capability is such that it’s going to be months before they have a substantial number of doses, and even then they’re going to be limited.”

“We’re hearing that the administration of this cocktail of antibodies improved both Dr. Brantly and Ms. Writebol, but you know, we don’t know that,” Fauci said, noting the sample size (two) of this small, ad hoc study. Proving effectiveness would require a much larger group of patients being compared to an untreated group. “And we don’t know that they weren’t getting better anyway.”

Thanks to Kebmodee for bringing this to the attention of the It’s Interesting community.

http://www.theatlantic.com/health/archive/2014/08/the-secret-ebola-treatment/375525/

Mysterious fever virus reported in Guinea

On By A.P.In Africa, CNN, Da Brayn, death, fever, Guinea, Medicine, microbiology, Science, Susanna Capelouto, virology, Virus1 Comment

By Susanna Capelouto, CNN
Since February 49 people have gotten sick and 29 have died from an unidentified illness characterized by fever, diarrhea and vomiting in Guinea, according to the West African nation’s minister of health, Remy Lamah.

Lamah said initial test results confirm the presence of a viral hemorrhagic fever, which according to the U.S. Centers for Disease Control and Prevention refers to a group of viruses that affect multiple organ systems in the body.

The Guinean health ministry warned in a statement that the disease is mainly spread from infected people, objects belonging to ill or dead people and by the consumption of meat from animals in the bush.

So far, most of the cases have been in the forest area of southern Guinea, and health officials say they are offering free treatment for all patients.

They’ve urged people to stay calm, wash their hands and report all cases to authorities.

http://www.cnn.com/2014/03/22/world/africa/fever-epidemic-guinea

Thanks to Da Brayn for bringing this to the attention of the It’s Interesting community.

MERS-CoV: Middle East respiratory syndrome coronavirus – poorly understood and on the rise

On By A.P.In Albert Osterhaus, CDC, coronavirus, Coronavirus Study Group, Erasmus Medical Center, France, Haj pilgrimage, International Committee on Taxonomy of Viruses, Margaret Chan, Medicine, MERS-CoV, Middle East respiratory syndrome coronavirus, Saudi Arabia, The Netherlands, U.S. Centers for Disease Control and Prevention, Virus, WHA, WHO, World Health Assembly, World Health Organization1 Comment

MERS-CoV

Saudi Arabia reported today that five more people have been infected with the Middle East respiratory syndrome coronavirus (MERS-CoV), as if to underline yesterday’s warning from the head of the World Health Organization (WHO) that the novel virus is a global threat.

In a brief statement, the Saudi Ministry of Health (MOH) said, “Within the framework of the epidemiological surveillance of the novel Coronavirus (MERS-CoV), the Ministry of Health (MOH) has announced that five novel Coronavirus cases have been recorded among citizens in the Eastern Region, ranging in age from 73 to 85 years, but they have all chronic diseases.”

Also, two more deaths from MERS have been reported in the past few days. Yesterday Agence France Presse (AFP) reported the death of France’s first MERS-CoV patient, a 65-year-old man whose illness was first reported on May 8. And on May 26 the Saudi MOH announced the death of an 81-year-old woman.

With today’s Saudi announcement, the unofficial global case count has reached 49; the death toll stands at 24, according to the US Centers for Disease Control and Prevention (CDC). Unofficially, Saudi Arabia has had 37 cases, with 18 deaths.

WHO concern
Deep concern about MERS-CoV was expressed yesterday by WHO Director-General Margaret Chan, MD, MPH, as she closed the annual World Health Assembly (WHA), the WHO’s policy-making body.

“Looking at the overall global situation, my greatest concern right now is the novel coronavirus,” she said as quoted in a WHO press release. “We understand too little about this virus when viewed against the magnitude of its potential threat. Any new disease that is emerging faster than our understanding is never under control.

“These are alarm bells and we must respond. The novel coronavirus is not a problem that any single affected country can keep to itself or manage all by itself. The novel coronavirus is a threat to the entire world.”

The WHO plans to send a second team to Saudi Arabia in coming weeks to help investigate the mysterious virus, according to a May 25 Arab News story that quoted Chan. The source of the pathogen remains unknown, but several case clusters have shown that it can spread between people in close contact.

“Without that proper risk assessment, we cannot have clarity on the incubation period, on the signs and symptoms of the disease, on the proper clinical management and then, last but not least, on travel advice,” Chan told Arab News.

The WHO, which sent a group of experts to Saudi Arabia earlier this month, will provide a fresh risk assessment ahead of this year’s Haj pilgrimage, which will take place in October, the story said.

Details on deaths
Concerning the five new cases, the Saudi MOH left many questions unanswered, including whether the patients are part of a hospital-centered outbreak of MERS-CoV that began in April in the Al-Ahsa region of Eastern province. The cluster has been reported to include 22 cases with 10 deaths. The statement gave no information on the patients’ conditions, gender, where they live, or how long they have been sick.

The French patient who died became ill on Apr 23, six days after he returned home from a vacation in Dubai, United Arab Emirates. Another person contracted the virus after sharing a hospital room with him from Apr 27 to 29.

The 81-year-old Saudi woman who died was among the previously announced cases in Al-Ahsa governorate, the Saudi MOH said in a May 26 statement. It said she was suffering from chronic kidney failure and other chronic diseases.

Her case appears to be the one announced by the WHO on May 18. That announcement said the 81-year-old’s illness was the 22nd case in the hospital-centered cluster in Al-Ahsa.

The May 26 MOH statement also said that nine other case-patients have recovered and been discharged from hospitals since the first MERS-CoV in Saudi Arabia, which occurred in June 2012.

MERS-CoV designation
In other developments, the WHO announced today that it is accepting the name MERS-CoV for the novel virus, despite a general aversion to geographic references in the names of newly discovered viruses.

“Given the experience in previous international public health events, WHO generally prefers that virus names do not refer to the region or place of the initial detection of the virus,” the agency said in a statement. “This approach aims at minimizing unnecessary geographical discrimination that could be based on coincidental detection rather than on the true area of emergence of a virus.”

The name was proposed by the Coronavirus Study Group of the International Committee on Taxonomy of Viruses, the WHO noted. The statement said the term emerged from consultations with a large group of scientists and represents an acceptable consensus

Patent issues
Also today, a story in BMJ offered more details on intellectual property issues related to MERS-CoV. Albert Osterhaus, DVM, PhD, head of viriology at Erasmus Medical Center in the Netherlands, told the journal that Erasmus has applied for patents on MERS-CoV genetic sequences and on possible related products such as diagnostics and vaccines.

Erasmus scientists were the first to analyze the virus and identify it as novel last year, after an Egyptian physician working in Saudi Arabia sent them a sample. Last week Chan and Saudi officials complained that restrictions imposed by Erasmus on use of MERS-CoV samples that it has supplied to other labs were impeding the investigation of the outbreak.

Erasmus officials have rejected the criticism and said they have supplied samples to all labs that want to use it for public health research and are equipped to handle if safely. But Osterhaus told BMJ, “We have patent applications submitted and that is on the sequences and the possibilities to eventually make diagnostics, vaccines, antivirals, and the like. It’s quite a normal thing if you find something new to patent it.”

He added that Erasmus has not made a deal with any company yet, because it’s too early. “At the end of the day, if you want something to happen for the benefit of public health—including making a vaccine, antivirals, whatever—you need to have at least some intellectual property. Otherwise the companies will not be interested,” he said.

http://www.cidrap.umn.edu/cidrap/content/other/sars/news/may2813corona.html

New SARS-like virus can infect both humans and animals

On By A.P.In ACE2, Bat, Chinese horseshoe bats, Christian Drosten, coronavirus, Emory University School of Medicine, Erasmus MC, Georgia, Germany, hCoV-EMC, human coronavirus-Erasmus Medical Center, Jordan, Larry Anderson, mBio, Middle East, Netherlands, pneumonia, Qatar, Rotterdam, SARS, SARS outbreak, Saudi Arabia, University of Bonn Medical Center, virologist, virology, VirusLeave a comment

sn-coronavirus

 

A SARS-like virus discovered this summer in the Middle East may infect more than just humans. The pathogen, a close cousin to the one that caused the 2002 to 2003 SARS outbreak, may also be able to infect cells from pigs and a wide range of bat species, researchers report today. The findings may help public health officials track the source of the outbreak and identify the role of wild animals and livestock in spreading the virus, researchers say.

Scientists first detected the virus in a 60-year-old man from Jeddah, Saudi Arabia, who developed severe pneumonia this past spring. Unable to identify the microbe causing the illness, doctors sent samples to Erasmus MC in Rotterdam, the Netherlands. There, scientists identified the infectious agent as a coronavirus, a group known to cause many ailments, such as the common cold and a variety of gastrointestinal infections. Cases have popped up in Qatar and Jordan as well; in total, researchers have so far confirmed nine infections, including five deaths. Several other cases are suspected but haven’t been confirmed.

Researchers have fully sequenced the virus, which they dubbed hCoV-EMC (short for human coronavirus-Erasmus Medical Center). The genome revealed that it is closely related to the SARS coronavirus.

The new study, published online in mBio, is an attempt to answer other basic questions, such as where the virus originated, how it enters cells, and what other animals it might infect, says Christian Drosten, a virologist at the University of Bonn Medical Center in Germany and one of the lead authors.

Scientists knew that the SARS virus uses a receptor called ACE2 to pry open cells. Because these receptors are mainly found deep inside the human lung, patients developed very severe illness that frequently left them too sick to spread SARS to many others; the people most at risk were health care workers who take care of patients. If hCoV-EMC used the same receptor, researchers would have a head start in understanding how it spreads and how to stop it—primarily by protecting health care workers. It might also help them in the development of drugs and vaccines.

To find out, the team engineered baby hamster kidney cells to express the human ACE2 receptor. These cells could be infected with the SARS coronavirus, as expected, but not hCoV-EMC. That finding, supported by additional experiments, led them to conclude that the new coronavirus does not use ACE2 to get in. Which receptor it uses instead is still unclear, which is a “downside” of the new study, says Larry Anderson, an infectious disease specialist at Emory University in Atlanta.

Epidemiologists also want to know which species of animals it is capable of infecting to keep the new coronavirus from spreading further. To determine what types of animals hCoV-EMC can infect, Drosten and colleagues infected cells from humans, pigs, and a wide variety of bats, the key natural reservoirs of coronaviruses. The new virus could infect all of these types of cells. “It’s unusual for a coronavirus to easily go back to bats,” Drosten says. “Most coronaviruses come from bats, but once they jump to other species, you could never get them to reinfect bat cells.” The SARS virus, for instance, originated in Chinese horseshoe bats, but once it ended up in humans, it had changed so much that scientists were unable to infect bat cells with it.

“The fact that [hCoV-EMC] can infect bat cells is consistent with the hypothesis that bats might be the origin of this virus, but this finding doesn’t prove it,” Anderson says. “This virus had to come from an animal source—there’s no other explanation for what’s going on. But we still don’t know what that source is.”

Based on the findings, however, it seems likely that the new coronavirus can infect a wide range of species, Drosten says. That means public health officials may have to start looking for infections and deaths in local wild animal and livestock populations to keep the virus in check, he says.

http://news.sciencemag.org/sciencenow/2012/12/new-sars-like-virus-infects-both.html?ref=hp

New virus discovered in Missouri

On By A.P.In CDC, Missouri, mosquito, phlebovirus, sandfly, Severe Fever with Thrombocytopenia Syndrome Virus, SFTSV, Tick, Virus, William NicholsonLeave a comment

 

 

 

It started with fever, fatigue,  diarrhea and loss of appetite.

But for two farmers in northwestern Missouri, the severe illness that followed a tick bite led epidemiologists on a journey to a new viral discovery.

“It’s brand new to the world,” said William Nicholson with the National Center for Emerging and Zoonotic Infectious Disease at the U.S. Centers for Disease Control and Prevention.

“It’s unique in that it’s never been found elsewhere and it is the first phlebovirus found to cause illness in humans in the Western Hemisphere. At this point we don’t know how widespread it may be, or whether it’s found in other states. We don’t know how many people in Missouri may have had this virus, as the finding of a completely new virus was a surprise to us.”

Nicholson, one of the authors of the report detailing the two cases published Wednesday in The New England Journal of Medicine, suspects the new virus is a member of the tick-borne phlebovirus and is a distant cousin to Severe Fever with Thrombocytopenia Syndrome Virus (SFTSV), a virus found in central and northeastern China and known to cause death in 13 to 30% of patients.

There are more than 70 distinct viruses in the phlebovirus family, and they’re grouped according to whether they are carried and transmitted by sandflies, mosquitoes or ticks.

“We’re not saying at this point that it is tick-borne,” Nicholson said. “We suspect ticks. It might be a lone star tick or another tick, but we have not ruled out sandflies or mosquitoes.”

According to Nicholson, this new virus “clusters genetically” – or is very similar, yet distinct – to other tick-transmitted phleboviruses and more distantly with the sandfly and mosquitoes. Researchers identified it by genetically sequencing the entire genome of the virus and comparing it to existing viral genomes.

“We’re casting a wide net so we can really figure out where this virus is located and how it’s being transmitted,” he said. “We are also going to be doing laboratory studies to learn more about the biology of the virus and how it might be transmitted.”

One farmer was a healthy 57 year-old man; the other, a 67-year-old man with type II  diabetes. Recovery for both farmers was slow. Both were hospitalized for about two weeks in 2009, and took about a month and a half to recovery fully.

It’s unknown whether this new virus can be transmitted from person to person, but no family members or caregivers reported symptoms similar to either patient.

At the moment, Nicholson said, there is no cause for concern. “I don’t think anyone should be worried. We are not worried … we are curious of what role the virus plays in human disease.”

To that end, an epidemiological study is underway in western Missouri, where researchers hope to identify new patients with similar symptoms. For now, researchers will turn their attention to the large number of vertebrae hosts maintaining the virus in nature – mammals both wild and and domestic, as well as birds. In the fall, they will check out the deer and wild turkey population.

Tick-borne diseases are on the rise in the United States. And while this new disease might not be tick-borne, ticks are the number-one suspect. Nicholson says people should use repellent, check themselves for bites or ticks, and avoid certain areas – if possible – that might serve as good habitats for ticks, such as wooded areas and areas with fallen leaves.

http://thechart.blogs.cnn.com/2012/08/30/new-virus-found-in-missouri-ticks-suspected/?hpt=hp_bn12

 

Ebola-like virus identified as cause of inclusion body disease that twists snakes into knots revealed

On By A.P.In arenavirus, boa constrictor, California, Ebola, Ebola-like virus, filovirus, inclusion body disease, Mark Stenglein, python, reptile, San Francisco, Snake, Steinhart Aquarium, UCSF, University of California, VirusLeave a comment

Scientists have finally found the cause of a mysterious disease that makes snakes tie themselves up into knots, stare off into space, and waste away—the reptiles are infected with an Ebola-like virus, a new study says.

The fatal condition known as inclusion body disease (IBD) was first diagnosed in snakes, particularly pythons and boa constrictors, in the 1980s.

Snakes diagnosed with IBD will often exhibit behavioral abnormalities, including an inability to flip over when turned on their backs and “stargazing,” which involves staring off into space and weaving their heads back and forth as if drunk. They are also more likely to contract other diseases, such as bacterial infections in their mouths.

Infected snakes often refuse to eat, or regurgitate their food when they do.

“They begin to waste away,” said study co-author Mark Stenglein, a biochemist at the University of California, San Francisco.

Scientists have long suspected a virus was behind IBD because the disease can be transmitted between snakes and is characterized by the buildup of proteins in cells, a feature of a number of viral diseases, Stenglein said.

But direct proof that a viral agent is responsible has been lacking-until now.

(Also see: “Python Hearts Double in Size—Now We Know Why.”)

Decoding the Snake Virus

Stenglein and his team analyzed the genetic material of snakes infected by IBD at the Steinhart Aquarium in San Francisco during a recent outbreak.

In addition to the known snake genome, they found genetic material belonging to a previously unknown virus. (See snake pictures.)

It appears to be most closely related to a class of viruses known as arenaviruses, that have only been known to infect mammals, namely rodents and people. However, the new virus doesn’t fit into the two categories of arenaviruses-New World and Old World-that are currently known.

The snake virus also contains a gene closely related to one found in the Ebola virus, which belongs to a different class known as filoviruses. Ebola, one of the most contagious known viruses, causes death through severe hemorrhaging when it infects humans.

The fact that that the new snake virus contains aspects of two completely different classes could mean that its origins stretch back tens of millions of years.

If that’s true, the snake virus is at least 35 million years old, said Stenglein, whose study appeared in August in the journal mBio.

Another possibility, the team says, is that the snake virus was created by a more recent merger of an arenavirus and a filovirus.

(See “‘Zombie Virus’ Possible via Rabies-Flu Hybrid?”)

David Sanders, an Ebola researcher at Purdue University in Indiana, called the new discovery “exciting,” but said he does not think the new virus is likely to provide any new information about Ebola, which is itself a very mysterious disease with murky origins. (Read why scientists can’t cure Ebola.)

As for IBD, said Stenglein, there’s still no treatment or cure.

But the new discovery means that vets and zookeepers could soon have a diagnostic test to genetically screen snakes for the disease before introducing them to a collection.

http://news.nationalgeographic.com/news/2012/08/120822-snakes-virus-ibd-ebola-animals-science/