Not Tonight Dear, I Had Ebola

Edit 9/28/14

I've received some very valuable feedback on this post and I agree that I should have started off with the science behind my opinion and included references. I intended to include references when I posted it, but got distracted and then forgot they weren't there. But without a rundown of what we know regarding infectious semen of surviving men, it wouldn't have been all that helpful. This is what happens when I write out of frustration and post while multi-tasking. Lesson learned.

I apologize and have edited the post to correct this. I've added references and a section with the heading "So what does science tell us about this topic" with a summary of what we know about infectious semen and transmission among survivors. I also realized I should have used the word “unprotected” in the sentence that really drives home the entire point of this post, and you will find that this sentence now has the word *unprotected* in asterisks in the text.

In addition, I added a final point regarding prostitutes (as a post script), based on a discussion on reddit. I am thrilled that this post has engendered so much discussion and I hope these changes have made it a bit clearer. I would also invite you to feel free to begin discussions here. As ever, thanks for stopping by!

Heather

Original Post:

I have fielded a lot of questions regarding Ebola virus in the semen of survivors lately and the
preponderance of people claiming this is a significant source of Ebola transmission is staggering. There is great concern and fear over this. Someone on Twitter was even genuinely concerned that these male survivors are "new highly infectious vectors" that weren't being calculated into projected disease spread. I'm a bit speechless really. Ok, maybe not that speechless.

And last night it was raging on Twitter:
Science based #Ebola horror: survivors have infectious semen for months

Maybe it's under the radar?

In large urbans after millions infected, who knows?

Counseling people on the dangers of sex post-Ebola is great but we know how people are. Who's to say they are obeying doctors orders about this?

So what does the science tell us about this topic? (added 9/28/14) Well, what we do know is from previous outbreaks and follow up with recovered patients. These are the scientific facts upon which my opinions on this are based:

• Evidence of Ebola virus can be found in semen up to 91 days post disease onset (1, 2, 3, 4)
• Not all surviving men have detectable virus in their semen.(2)
• Of those who do, not all of them have it there for 91 days. Some have been found negative at 45 days.(2)
• Men who’ve recovered are counseled by their physicians about the dangers of transmitting Ebola to sexual partners through unprotected sex. (3)
• One study found indirect evidence that one woman may have gotten Ebola from sex, but they could not confirm that she actually had Ebola, or that she got it from sex. (1)
• There is anecdotal evidence that one woman got Ebola from sex during this epidemic
• Dr. Barbara Knust, an epidemiologist at the Centers of Disease Control and Prevention answered this question for NPR and said this: “Ebola is spread only by people exhibiting symptoms and through direct contact with bodily fluids. Once a person recovers from Ebola virus disease, he or she is no longer shedding virus, and thus is not contagious. In past Ebola outbreaks, follow-up studies of patients who have recovered from Ebola and their contacts found no evidence that the Ebola virus was spread from a recovered patient to their close contacts.”
• And in response to the specific question about semen:
• “Therefore, male survivors of Ebola are advised to avoid having sex for three months or to use condoms. Semen and breast milk are not the primary means by which Ebola is transmitted. The virus is primarily transmitted via blood, sweat, feces and vomit.”
• Dr. William Schaffner, a professor of preventive medicine and infectious diseases at Vanderbilt University Medical Center in Nashville, Tennessee had this to say of it. "Of all the modes of transmission, that's going to be the last," Schaffner told Live Science. "It's a little like asking me, 'If we're all going to go from New York to San Francisco, will one of us walk?' That doesn't happen too often."

Are we on the same page now?
Great.

OK. Let's think about this for a minute. No I mean really think about it. Let's think about the average male survivor in West Africa, what he's been through, who he may have lost to Ebola and how he's feeling physically after battling for his life either at home or in a terrifying Ebola ward. Are you thinking? Really thinking?

How would you feel?

Let's say, worst case scenario this man lost some loved ones, family members or friends. He most likely tried to help or watched at least one of those die. Then he got sick himself and ended up in an Ebola ward. He was terrified and thought he would die. But he didn't. He survived and was released. (read about one man's Ebola survival tale that depicts this clearly.)

So is this where you think the party begins? I hardly think so. This is just the beginning of a whole new set of problems for this guy.

This man has to go back home and continue to recover. Recovery from Ebola hemorrhagic fever takes time, sometimes a lot of it. (And yes, I know we call it Ebola virus disease now, but that does little to communicate the severity of this condition, so I'm sticking with EHF - check out the diagram on the right to see what I mean).

Most likely he'll be welcomed from a distance by any family he has left. Do you really think the single ladies are lining up to give him a Hero's welcome? If they were, do you really think he'd be in the mood? You think maybe he will need some time to cope with what he's been through and with what he's lost?

What are the chances he lost his wife if he had one? Pretty good, I'd say. If both got sick, if at least 50% die and he survived. Even if he didn't lose her, do you think he's not imagining what might happen to her if he gave her Ebola through sex? Do you really think, after everything he's been through and seen, with more and more bodies, and more and more people turned away from treatment centers, that he's going to actually feel like having sex, let alone risk someone's life for it?

Let's say the man is single and has lost no one close to him. Do you think the ladies will be lining up for him either? Do you think he hasn't seen and experienced the same kind of hell? Do you really think that, in the middle of the death, loss, hopelessness and terror of the worst Ebola epidemic the world has ever seen, he doesn't care if he infects another person?

In voicing these concerns, do you have any idea how ugly the assumptions you've made about the character of Ebola survivors truly are?

Survivors are being scorned, avoided and worse. Ebola volunteers are being murdered out of fear and ignorance. Do you really think surviving men, men who are still physically and emotionally recovering, are having enough *unprotected* sex while infectious to be a significant source of transmission?

I don't. I think for the most part these men are exhausted and scared. I think they wish they were stronger so they could help more. I think they are worried about providing for themselves and their families while being isolated within cities that aren't functioning well. I think they are thinking about those they infected while they were sick, wondering who among them will die and when.

I keep saying this because it bears repeating: there's no need to look for Zebras here. The out-of-control transmission of Ebola virus in this epidemic is from the well known and documented routes of transmission, while people are sick and symptomatic, not after they've recovered. Why argue for anything else and add to the already traumatized and stigmatized survivor's burden?

We can do better than that.

We must do better than that.


Pathogen Scribe


Post Script:

This discussion continues on reddit and like I said has provided valuable feedback. I’d like to address one particular comment in response to this post:

"I think Heather underestimates the extent to which the "comfort" of a woman has become habitual to many men. A Couple of weeks after being "cured", an over-stressed man might very well revert to that familiar source of psychological balm. She assumes a setting in which potential partners know the survivor, not an urban setting. Infection of prostitutes is not out of the question.”

I would like to take this opportunity first to say thanks for reading and for commenting. And you’re right I should have addressed the idea of prostitutes. However, it would not have changed my point. In fact, if you really think this will cause transmission via semen to be a significant source of transmission (the point of the post) then these are the assumptions you’ve made:

1) A majority of men who’ve recovered from Ebola will forego doctor’s orders and risk infecting others, including prostitutes, because they want the “psychological balm” of unprotected sex more than they want to stop the spread of Ebola.

2) These men are also willing to risk any of the other sexually transmitted diseases that can be spread by unprotected sex with strangers or prostitutes.

3) The women in question, including prostitutes won’t demand the use of protection during sex with a stranger.

And you’re assuming that enough of this will happen to make the spread of Ebola through semen a significant mode of transmission.

Like I said before, we can do better.

References

1) Alexander K. Rowe, Jeanne Bertolli, Ali S. Khan,Rose Mukunu, J. J. Muyembe-Tamfum, David Bressler, A. J. Williams, C. J.Peters, Luis Rodriguez, Heinz Feldmann, Stuart T. Nichol, Pierre E. Rollin andThomas G. Ksiazek for the Commission de Lutte contre les Epidémies à KikwitClinical,virologic, and immunologic follow-up of convalescent Ebola hemorrhagic feverpatients and their household contacts, Kikwit, Democratic Republic of theCongo. Commission de Lutte contre les Epidemies à Kikwit. J Infect Dis 1999;179(Suppl 1):S28-35.

2) Daniel G. Bausch, Jonathan S. Towner, Scott F.Dowell, Felix Kaducu4, Matthew Lukwiya, Anthony Sanchez, Stuart T. Nichol, Thomas G. Ksiazek and Pierre E.Rollin. Assessment of the Risk of Ebola Virus Transmission from Bodily Fluidsand Fomites. J Infect Dis. (2007) 196 (Supplement 2): S142-S147.

3) R.T Emond, B Evans, ET Bowen, and G Lloyd. Br MedJ. Aug 27, 1977; 2(6086): 541-544. A case of Ebola virus infection.

4) L. L. Rodriguez, A. De Roo, Y. Guimard, S. G. Trappier,A. Sanchez, D. Bressler, A. J. Williams, A. K. Rowe, J. Bertolli, A. S. Khan,T. G. Ksiazek, C. J. Peters and S. T. Nichol. Persistence and Genetic Stabilityof Ebola Virus during the Outbreak in Kikwit, Democratic Republic of the Congo,1995. J Infect Dis. (1999) 179 (Supplement 1): S170-S176.

Ebola Convalescent Serum: It's No Magic Bullet

Hello Dear Friends,

There have been many questions since Dr. C.J. Peters was quoted here (9/8/14) saying that convalescent serum from Ebola survivors was unlikely to help treat patients. In this post I go into detail about the data we have that supports this statement. In a future post I will discuss the why of it.

OK. Much of what's been said in the media and by scientists gives the illusion that the effectiveness of Ebola convalescent blood as a treatment for Ebola virus disease is an established and recognized fact. WHO's endorsement and the New York Times article on it has, I think, given people some false hope. Don't get me wrong. West Africa is in a tough spot and I understand why it's being tried. Why not? What else do we have to offer these people? But that doesn't mean it will work. And while I strongly encourage doing everything we can think of to help people, in a situation with limited resources we should focus on those options with the most data to support them and avoid things that might make the situation worse. Since the WHO's announcement, survivor blood has become a hot commodity and now there's a black market for it. How many will suffer a second time because others will surely go to great lengths to get their blood? Blood that will most likely turn out to be unhelpful. But unfortunately, most looking at this situation (like me before I researched it) only know that convalescent serum can work really well for some viruses so they assume it's worth trying. Unfortunately all viruses are not created equal and if those considering this treatment actually looked at the data for Ebola they would see that it tells us this new treatment strategy will almost certainly fail. So let's take a look at this data.

(By the way, if you're confused about names and abbreviations for Ebola viruses you're not alone. For clarification check out Ian Mackay's explanation at Virology Down Under.)

First let's clarify something: what in the heck is "convalescent serum"? To understand what "serum" is, we need to know what blood plasma is, so let me quickly explain. Blood plasma is that light yellow liquid part of the blood that keeps whole blood cells in suspension (keeps them from settling). Plasma contains a lot of important things including, but not limited to, dissolved proteins, glucose, hormones and clotting factors. Blood plasma without the clotting factors is called "serum". Convalescent serum is then serum from the blood of a person who has recovered (convalesced) from an infection, such as a viral infection. This serum may or may not contain those dissolved proteins that could be helpful to fight an infection such as antibodies. Antibodies are proteins made in response to "foreign" bodies, such as viruses, and can help get rid of them. For more details about how antibodies are made and work read this post. You should also know that giving serum that is thought to confer immunity from one organism to another, is called "passive immunization" or "passive transfer". It's important to note here that convalescent serum can also contain drugs or microorganisms so it must be tested both for safety and effectiveness before giving it as a treatment.

As was mentioned in my Q&A with Dr. Peters, for some viruses such as Junin, the virus that causes Argentine hemorrhagic fever, we know that convalescent serum is very effective and is used on a regular basis(1-3). But what do we really know about the use of convalescent plasma or serum for Ebola patients?

Well what's been touted as hard evidence in the media lately are two specific instances in which Ebola patients were given convalescent serum and survived. Well OK then. We're done here right? Not so fast. Let's take a closer look at these cases.

A huge thank you to Mariella Furrer for allowing me to use this photo. Ms. Furrer is an award winning freelance photojournalist based between Kenya and South Africa who has spent her remarkable career documenting some of the most egregious human rights issues. She also documented the 1995 Kikwit Ebola outbreak. Read more about Mariella on my page dedicated to her and her work.

The first is the 1999 paper by Mupapa et al (4) that describes the treatment of 8 Ebola patients from the 1995 Kikwit outbreak. These patients received blood transfusions of whole blood donated by 5 convalescent patients. The blood was tested and found to have ELISA antibodies against Ebola and no viral antigen was detected. So in this case the patients received whole blood, not just serum, but the principle is the same and 7 of the 8 patients lived. WOW! So that blood really worked!! Well, not necessarily. You see, there's more at work here than just the blood transfusion. The authors of the paper  indicated that those 8 patients not only received blood transfusions, they got better supportive care, and with Ebola supportive care may keep you alive just enough for your body to fight the virus on it's own. In fact, another paper published in 1999, by Sadek et al (5), found that with Ebola, the longer you live the better your chances of survival. Sound obtuse? Well, they made a timeline for patients that included time of symptom onset and time of death or survival and it revealed a striking correlation between length of disease and survival: "In general, patients who survived the disease for at least 1 week had a probability of survival of 30%. The rate increased to ~70% for those who survived the first 2 weeks beyond the onset of symptoms." So when were the blood transfusions done? Well, they were done on day 10 post symptom onset. So those patients already had an increased probability of survival. And after adjusting the data for age, sex, and days after onset of symptoms, there was no statistical evidence of a survival benefit from the blood transfusions. Read the paper. Their methods and stats were robust. Furthermore, another paper discussing the same outbreak (6) had this to say, "Oral or intravenous rehydration, provision of adequate calories through oral food intake, and possibly treatment with antibiotics and antimalarial drugs to prevent infections are probably the most important measures to improve survival among EBO patients."

The second case that's been making the media rounds is that of lone virologist Geoff Platt who in 1976, while working with an unidentified virus that was similar to Marburg, accidentally stuck himself with a needle. You can read the paper about his case here (7), and there's a recent article that includes him here. According to the paper, within 24 hours of the first onset of symptoms he began receiving intramuscular injections of human interferon, a protein made by cells to fight viruses. His course of interferon treatment included 3 million units every 12 hours for 14 days. About 24 hours later he was given his first infusion of convalescent serum taken from patients who'd recovered from the 1976 Yambuku Zaire (now DRC) Ebola Zaire outbreak. It was learned later that the virus he'd been infected with was Ebola Sudan. Geoff recovered and in fact after the first infusion of serum the numbers of Ebola particles in his blood dropped significantly. Wow! That serum really worked!! Well, not so fast. You see, they were determining the amount of virus in his blood (viremia) using a guinea pig assay (2 guinea pigs per point). Because taking blood from an Ebola patient and sticking it into a guinea pig can be a bit scary, they didn't take many samples so the actual data from the viremia assay isn't reliable. So it's possible it didn't have as much of an effect as was deduced. This, combined with the fact that this man received interferon and excellent supportive care, makes it impossible to say definitively that it was the serum from the Zaire survivor that was responsible for his recovery (not to mention we have no evidence that different Ebola species provide cross protection).

So those are the cases being touted as proof that convalescent serum from Ebola patients is exactly what these suffering people need and yet, they don't really tell us that. But there is a lot more evidence that this strategy won't work including:

• During Kikwit outbreak, convalescent serum from Ebola survivors was given to cyncynomolgus macaques and it failed to protect any of the monkeys from challenge with EBOV. (unpublished data C.J.Peters., 1995)

• During Ebola vaccine study in guinea pigs, animals that were protected from lethal challenge were bled and their serum was given to naive animals. The vaccinated guinea pig donors all survived. Their serum failed to protect other guinea pigs; all died after Ebola challenge. (8)

• Passive immunization of cynomolgus macaques with high-titer equine immunoglobulin against Ebola Zaire failed to protect animals from lethal ZEBOV challenge (9,10)

• Passive immunization of rhesus macaques with high-titer anti-EBOV equine immunoglobulin failed to protect any of the animals from a lethal challenge and did not even delay death (P.B.J., unpublished data.)

• Passive transfer of a neutralizing human monoclonal antibody that completely protected guinea pigs against EBOV infection (11) failed to protect rhesus macaques against a lethal EBOV challenge (12).

• Transfusion of convalescent blood from EBOV-immune monkeys did not protect naive animals from challenge with EBOV, even though the transfused monkeys had as much antibody as those with effective vaccination. (13). This experiment was done on the off chance that the Kikwit donors had activated lymphocytes or some other substance in their whole blood that provided protection.

So when Dr. Peters said that there wasn't much evidence to support that Ebola convalescent serum would be effective, but that there was quite a bit of evidence to support that it would not, what I've outlined above is what he meant. And Tom Geisbert's group summed it up very nicely in their 2007 paper (13):

"However, the results of the present study, which used immune primate blood, joins the preponderance of published study results suggesting that immunotherapy will not be a shortcut to the solution. Given these discouraging results and the risks of transmitting infection, whole blood transfusions, even under desperate epidemic conditions, seem unwarranted."

As desperate as we are for a way to help these patients, we simply have no solid platform from which to proclaim Ebola survivor blood as effective therapy. With a black market for blood, my fear is that already stigmatized survivors will be further targeted. We have a responsibility to make sure people are informed. 

Cheers,

Pathogen Scribe


Postscript: C.J. Peters Take on This Post:

"I agree with [Pathogen Scribe]. During the Kikwit episode we were harangued to give plasma or have intravenous IgG prepared and I resisted because it diluted our other efforts in a time of scarce resources.  One should also consider that the oldest strain of HIV1 was isolated by Joe McCormick from Ebola convalescent plasma drawn for potential therapy before we knew anything about that virus.  There are also the usual considerations for problems with transfused plasma: antibodies against recipient blood cell antigens, aggregation of IgG activating complement, bacterial contamination, etc.  If plasma is harvested and returned to the developed world for testing and processing into pooled IgG there is the delay and also the problem of recipients reacting to aggregates in the plasma. 
            It seems much more valuable to look down another avenue for therapeutic modalities.  Pooling 3 human monoclonal antibodies to the Ebola glycoprotein with each reacting with a different epitope (14) has been tested in macaques.   When the recombinant vectors are grown in their tobacco leaf substrate and the immunoglobulins purified, this cocktail (ZMapp ) protects macaques (15) and would have a chance with infected humans.  There is also an antisense RNA and several antivirals which might be effective.  And don’t forget the use of anticoagulants such as activated protein C and nematode anticoagulant protein c2 that have had a sparing effect in non-human primates, suggesting that they or other substances working on the coagulation cascade and/or vascular  endothelium have potential (16, 17)."

Another HUGE thank you to C.J. for his incomparable insight and expertise!!


References

1.) D.A. Enria, A.M. Briggiler, N.J. Fernández, S.C. Levis, J.I.Maiztegui Importance of dose of neutralizing antibodies in treatment ofArgentine hemorrhagic fever with immune plasma. Lancet, ii (8397) (1984), pp.255–256.

2.) DeliaA. Enria, Julio I. Maiztegui. Antiviral treatment of argentine hemorrhagic fever.Antiviral Research Volume 23, Issue 1, January 1994, Pages 23–31.

3.) Delia A. Enria,  AnaM. Briggiler, Zaida Sánchez. Treatment of Argentine hemorrhagic fever. AntiviralResearch Volume 78, Issue 1, April 2008, Pages 132–139.

4.) K. Mupapa, M. Massamba, K. Kibadi, K. Kuvula, A.Bwaka, M. Kipasa, R. Colebunders and J. J. Muyembe-Tamfum on behalf of the International Scientific and Technical Committee. Treatment of Ebola Hemorrhagic Fever with Blood Transfusions from Convalescent Patients. J Infect Dis. (1999) 179 (Supplement 1): S18-S23.

5.) Ramses F. Sadek, Ali S. Khan, Gary Stevens, C. J. Peters and Thomas G. Ksiazek Ebola Hemorrhagic Fever, Democratic Republic of the Congo,1995: Determinants of Survival. J Infect Dis. (1999) 179 (Supplement 1):S24-S27.

6.) Guimard Y, Bwaka MA, Colebunders R, Calain P, MassambaM, De Roo A, Mupapa KD, Kibadi K, Kuvula KJ, Ndaberey DE, Katwiki KR, MapandaBB, Nkuku OB, Fleerackers Y, Van den Enden E, Kipasa MA. Organization ofpatient care during the Ebola hemorrhagic fever epidemic in Kikwit, DemocraticRepublic of the Congo, 1995. J Infect Dis. 1999 Feb;179 Suppl 1:S268-73.

7.) R.T Emond, B Evans, ET Bowen, and G Lloyd. Br Med J. Aug 27, 1977; 2(6086): 541-544. A case of Ebola virus infection.

8.) Xu L, Sanchez A, Yang Z, Zaki SR, Nabel EG, Nichol ST, Nabel GJ. Immunization for Ebola virus infection. Nat Med. 1998 Jan;4(1):37-42.

9.) Jahrling PB, Geisbert J, Swearengen JR, et al. Passive immunization of Ebola virus-infected cynomolgus monkeys with immunoglobulin from hyperimmune horses. Arch Virol Suppl 1996;11:135-40.

10.) Jahrling PB, Geisbert TW, Geisbert JB, et al. Evaluation of immune globulin and recombinant interferon-α2b for treatment of experimental Ebola virus infections. J Infect Dis 1999;179((Suppl 1)):S224-34.

11.) Parren PWHI, Geisbert TW, Maruyama T, Jahrling PB, Burton DR. Pre- and postexposure prophylaxis of Ebola virus infection in an animal model by passive transfer of a neutralizing human antibody. J Virol 2002;76:6408-12.

12.) Oswald WB, Geisbert TW, Davis KJ, Geisbert JB,Sullivan NJ, et al. (2007) Neutralizing Antibody Fails to Impact the Course of Ebola Virus Infection in Monkeys. PLoS Pathog 3(1): e9. 

13.) Peter B. Jahrling, Joan B. Geisbert, James R.Swearengen, Thomas Larsen and Thomas W. Geisbert. Ebola Hemorrhagic Fever: Evaluation of Passive  Immunotherapy in Nonhuman Primates J Infect Dis. (2007) 196 (Supplement 2): S400-S403.

14.) Bale S1, Dias JM, Fusco ML, Hashiguchi T, Wong AC, Liu T,Keuhne AI, Li S, Woods VL Jr, Chandran K, Dye JM, Saphire EO. Structural basisfor differential neutralization of ebolaviruses. Viruses. 2012 Apr;4(4):447-70.doi: 10.3390/v4040447. Epub 2012 Apr 5

15.) Xiangguo Qiu, Gary Wong, Jonathan Audet, AlexanderBello, Lisa Fernando, Judie B. Alimonti, Hugues Fausther-Bovendo, Haiyan Wei, Jenna Aviles, Ernie Hiatt, AshleyJohnson, Josh Morton, Kelsi Swope, Ognian Bohorov, Natasha Bohorova, CharlesGoodman, Do Kim, Michael H. Pauly, Jesus Velasco, James Pettitt,    Gene G. Olinger, Kevin Whaley, Bianli Xu, James E. Strong, LarryZeitlin & Gary P. Kobinger. Reversionof advanced Ebola virus disease in nonhuman primates with ZMapp. Nature (2014) Publishedonline 29 August 2014.

16.) Hensley LE1, Stevens EL, Yan SB, Geisbert JB, Macias WL,Larsen T, Daddario-DiCaprio KM, Cassell GH, Jahrling PB, Geisbert TW. Recombinanthuman activated protein C for the postexposure treatment of Ebola hemorrhagicfever. J Infect Dis. 2007 Nov 15;196 Suppl 2:S390-9.

17.) Geisbert TW1, Hensley LE, Jahrling PB, Larsen T, GeisbertJB, Paragas J, Young HA, Fredeking TM, Rote WE, Vlasuk GP. Treatment of Ebolavirus infection with a recombinant inhibitor of factor VIIa/tissue factor: astudy in rhesus monkeys. Lancet. 2003 Dec 13;362(9400):1953-8.

Ebola Q & A with Dr. C.J. Peters: What My Tweeps Want to Know

Dear Friends,

The response to my Fireside Chat with Dr. C.J. Peters was even better than expected and I got a lot of great feedback from my blog readers and Twitter friends. I'd like to thank all of you for taking the time to read this blog and for engaging in such great dialogue about it. It really adds a rewarding dimension to the whole experience.

Many of you had additional questions for C.J. regarding the current Ebola epidemic. I asked him if he'd mind answering them for you here and he was happy to do so. I had to limit the questions so I selected them on a first-come, first-served basis. Several had the same or similar questions, but if I missed anything you think is critical, let me know and I will add it when I can.  Enjoy!

Our first three questions are from Dr. Ian Mackay, a virologist at the University of Queensland who is also the Keeper for both the site and blog for Virology Down Under. Dr. Mackay can be followed on Twitter: @MackayIM and I recommend it. In fact his was the first blog on my blog roll here.

Dr. Mackay: Given this outbreak is very different from previous ones - because of human factors -does what's needed to control it also have to be different?
Dr. Peters: Nobody knows. There's no indication initially that this EBOV is any more infectious than any other EBOV that we've dealt with, but it's something that should be studied using the control methods that worked with the previous outbreaks. There's no indication they wouldn't work but you gotta look.



Dr. Mackay: Following up on that question, what are the top 3 things that could be done, or done better, to contain this outbreak?
Dr. Peters: 1) More training paramedical people. 2) Provide more PPE 3) Rethink the approach. Should we be concentrating on infected areas or areas adjacent to those infected areas? We could superimpose a map of infected areas over a satellite map of the region and ring the infected areas. The adjacent areas could then be given PPE and training, not to contain it but to get on top of it. And quarantine strategy needs to change. People need to be fed and provided for. There's no panacea, they need more PPE and more equipment and currently the major worry is dealing with problems already there. An adequate response will require the whole world to step in, including the U.S. military who are more than capable of setting up field hospitals for highly infectious diseases. Also helpful would be involving anthropologists to interact with locals and help with communications - like how do you tell people what you need them to do and get them to do it?

Dr. Mackay: Have you had a chance to look at the sequence changes from the Sierra Leone genomes? If so, do any look worrying to you for phenotypic change?
Dr. Peters: We don't have the experience we need to be able to answer this. You can't tell that from the sequence unless you have experience with the given virus and with those sequence changes. We've only recently gotten to a point with influenza where we can predict what's worrisome and that's been studied by many smart people for a long time. When discussing the importance of the human genome project, people said it would provide all the words in the dictionary of human genetics. But that dictionary is only helpful if you have the definitions to go with the words. We don't have all the definitions for EBOV sequences. We just don't have the experience it takes to tell at this point.

Our next two questions are from Stephen Goldstein, ScM. Stephen is a Science News Analyst at Public Health United and a PhD student in virology at the University of Pennsylvania. He can be followed on Twitter: @stgoldst.

Stephen: Do you have any thoughts on the case fatality rate disparities between the affected countries?
Dr. Peters: No. And that's a good question. It may be a situation in which case ascertainment is not accurate, but it may be real.

Stephen: What do you make of the studies showing high seroprevalence for EBOV with no indication of illness? Subclinical infections?
Dr. Peters: I think the IFAs are totally unreliable. I've done them myself for Ebola Zaire and Reston, from monkeys and humans and they didn't tell us anything. They are just unreliable. I don't think it means that there were a bunch of subclinical infections, I think it means the test was unreliable.

(ME: C.J. and I discussed these papers for a bit, as well as his experiences with it. I was surprised to learn that even with really good controls and technique the method really isn't reliable for drawing any kind of conclusion about Ebola in this regard. )

Our next questions come from Michael Owen, a regulatory microbiologist from Washington State. Michael is a biosafety enthusiast who has compiled a nice Ebola resources webpage and he can be followed on Twitter: @owenmp.

Michael: In the field, do Ebola HCW need to collect disinfectants used to decontaminate hospital areas and used PPE? How could you do this?
Dr. Peters: Clorox is readily available and effective so they should use it when possible. People who could get exposed should have the right PPE, but if not, then they need to use what they can. Ethleen Lloyd put together a manual in 1998 to help improvise PPE for VHF in an African setting. It's available for download on the CDC website but they haven't utilized it during this epidemic. We could also face shortages of PPE for this. There were shortages with SARS and it's a possibility.

Michael: Is there a minimum time to wait between complete EVD recovery and harvesting blood from a survivor for passive therapy?
Dr. Peters: This is not known for Ebola, but blood/serum from a survivor won't help here anyway. There's no evidence that it will help, but strong evidence that it won't help. For other viruses it can be critical, such as for the arenavirus Junin, for which it is used effectively on a regular basis. But for Ebola it's just not effective. For Junin, they wait until 3 months after illness to harvest serum for therapy, but they don't know that 3 months is required, they just know that 3 months works.

(ME: I was one of the first to suggest that passive immune therapy might help with this epidemic and I was surprised at this, but now have a better understanding. Because this is currently making headlines I will be addressing it in a post soon.)

One final question I asked, on behalf of the fear-mongering doomsayers on Twitter: :Is this Ebola epidemic a threat to humanity?
Dr. Peters.: No. It may very well decimate Africa. Africa is in real trouble, but it is not a threat to humanity and it won't cause a pandemic.

ME: There. You heard that from the Quintessential Virus Hunter himself. And please don't mistake this for denial that this Ebola epidemic is a global problem...it's definitely a global problem. We've already clearly stated that this is a problem that absolutely requires a global response effort. But that's not the same as claiming it will cause a pandemic or destroy humanity. We good? Good.

A HUGE thank you to my Tweeps who came up with some great questions and an even bigger thank you to C.J., for being so willing to clarify these issues and help us understand this epidemic.

Cheers,

Pathogen Scribe


References

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Sullivan NJ1, Sanchez A, Rollin PE, Yang ZY, Nabel GJ.Development of a preventive vaccine for Ebola virus infection in primates. Nature.2000 Nov 30;408(6812):605-9.

Wendelien B Oswald, Peter B. Jahrling, Joan B. Geisbert,James R. Swearengen, Thomas Larsen and Thomas W. Geisbert. Ebola HemorrhagicFever: Evaluation of Passive  Immunotherapy in Nonhuman Primates J InfectDis. (2007) 196 (Supplement 2): S400-S403.

Oswald WB, Geisbert TW, Davis KJ, Geisbert JB,Sullivan NJ, et al. (2007) Neutralizing Antibody Fails to Impact the Course of Ebola Virus Infection in Monkeys. PLoS Pathog 3(1): e9.