A single line often inverts meaning once you see what it
answers, so neighbouring messages are always shown.
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August 21, 2014 - 2 secondary cases of Ebola (beyond cluster of health care workers) from the index in Nigeria. Getting close on agreement with Tom Frieden. Cliff Lane very helpful; in hammering out details with CDC people - Tim Uyeki and Steve Redd (Steve is a rally good guy with whom I dealt during the Flu issues). Continued press → MSNBC; WTOP radio; CNN with Lou Dobbs; BBC Newsday Radio.
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August 22, 2014 - Situation same with epidemic. Good news - have come to agreement with Tom Frieden on approach to Ebola vaccine following Phase1 trials. Agree to go for RCT with control group as first choice. There well may be obstacles on the ground to this approach including perception of keeping interventions from those who need it (even though we still do not know whether the vaccine is either safe or effective). This may necessitate a modified RCT without a control group or even skipping an RCT and going to emergency open access. The plan is to do a "rolling" approach staring with RCT → modified RCT → open access in priority order. I will present this to Secretary's call next week. Tom Leaves for West Africa over the weekend. Press still active → Fox 5 WTTG; CNN International; BBC Radio - The World; WNEW CBS Radio - NYC; PRI (BBC) - Boston - "The World" with Marco Werman
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August 23 - 27, 2014 - Still escalating Ebola situation. Now a secondary case in Nigeria with having infected a person who took care of him. That person (who recovered) then infected a doctor in Port Harcourt. The doctor died, but the doctor's wife is now infected. The numbers are going up. Tom Frieden now in Liberia to assess the situation. He is saying that it is catastrophic and out of control in a press conference from Monrovia. People on the Secretary's 3x per week call have criticized him for being "hyperbolic". How should they know - he is there and they are here. Typical government cover-your-ass bullshit. Still getting modest press.
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August 28, 2014 - Our big press teleconference announcing the beginning of the Ebola vaccine Phase 1 trial of the Chimp Adenovirus 3 vector with the Ebola GP bivalent gene insert. Trial to start on September 2 at NIH Clinical Center. Also coinciding with slightly later start of monovalent identical vaccine in the UK with Oxford, Wellcome Trust and extension into Mali and the Gambia. Also, we announced our collaboration with NewLink and Public Health Agency of Canada (PHAC) in a Phase 1 trial (in Silver Spring, MD with WRAIR) of the VSV - Ebola vaccine. Much press interest today with appearances on: Fox News Radio; Hearst TV; WTOP; MSNBC with Ronan Farrow; NBC Nightly News; The NewsHour; Cox TV; 24/7 National News Radio; CNN Anderson Cooper; Local Channel 9 News; AP TV.
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2014-08-28 00:00
Anthony S. Fauci
August 28, 2014 Nature paper on deep sequencing by Pardis Sabeti from the Broad in Boston showed phylogenetic origin of virus as a single point source. In the paper, the woman who brought the virus from Guinea to Sierra Leone got is at a funeral where she tended to a body; however, 12 people from that funeral got infected from 2 lineages, probably all having gotten infected at the funeral. It seems to me that these women did not all touch "macroscopically visible feces, blood or vomitus on the body. Someone or more initially cleaned the body, but certainly some kissed or otherwise touched what appeared to be a clean body and got infected. Conclusion, it is likely than microscopic contamination with residual bodily fluids on what appears to be clean skin or surfaces could spread the virus. Hypothetical scenario → person is infected and in early stage, get diarrhea and wipes his anal area, contaminates his hands with microscopic fecal material and virus, washes or not his hands, but virus remains and he then shakes someone's hands, serves someone food, etc. and transmission occurs I do not believe at all that it is transmitted by the respiratory route; however, inadvertent ure. contamination of hands outside of the classical hospital setting should in my mind at least be considered as a potential route of transmission. Press interest continues with: Columbia (Bogota) Radio; VOA TV; NPR Weekend Edition with Scott Simon; NPR Science Friday; CNN with Jake Tapper; Reuters TV
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August 29, 2014 - UK raises terror threat to Level 4 (of 5) due to activity of ISIS in Syria and Iraq, who are threatening the West. They have been brutally assassinating free Syrians (beheadings) and have shown a beheading of an American journalist (James Foley) on You Tube. Ebola - outbreak raging. Tom Frieden is obviously distraught. I am concerned about him as he is having a very emotional reaction to this. He wrote me an e-mail yesterday from Liberia saying that the situation is completely out of control and that health care workers are getting infected and we should distribute the vaccine even without Phase 1 safety data. This is not correct. We have to do at least a modicum of safety data before we distribute it. I am beginning to get concerned that transmissibility is not just confined to people who take care of sick people and who have "direct contact with bodily fluids such as Feces, Vomitus, blood, and urine". There have been some situations that have me believe that fomites and hand contact inadvertently with fomites outside of the "direct" healthcare setting might also spread the virus. Some examples: Dr. Brantley and Nancy Brighthol were both infected and Brantley was experienced in PPE. Of note, no MSF person who used PPE has ever gotten infected over years of taking care of Ebola patients. Nancy never directly took care of Ebola patients. the WHO person, likely got infected while taking care of patients, but did not tell anyone he was feeling poorly. He went to meetings with people from WHO, MSF, and other organizations and two of these people got sick and they did not breach any PPEs. got sick from his sister in Liberia, got on a plane and flew to Nigeria. Got sick in Nigeria and several health care providers who took care of him without PPE (~12) got sick and 8 died. One of the people who did not know he was sick went to Port Harcourt, got sick saw a physician. The physician got infected and ultimately died, but not without infecting his wife. The
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August 30, 2014 - Case from Guinea went to Dakar, Senegal and lied about exposure. Took bus and stopped in 2 health care facilities. Contact tracing now going on in Senegal. Spoke with Tom Frieden who is in Liberia. Trying to get him to appreciate that giving VSV Ebola vaccine as post-exposure prophylaxis (PEP) is risky due to the induction of cytokines by the live VSV, which might actually enhance the acquisition upon exposure since cytokine dysregulation plays a negative and potentially positive role in Ebola virus disease. He wants to pre-position VSV vaccine for PEP and TKM drug (siRNA - not yet is phase 1) at all Ebola treatment Units (ETUs). I understand the desire to protect the CDC and other health care workers on the front lines, but we must be concerned about giving drugs/PEP vaccines BEFORE they have even been in the earliest Phase 1 trials. Yesterday CDC evacuated a WHO worked who had a low risk needle stick (clean needle through potentially contaminated gloves) and they gave the person TKM drug and wanted to give VSV, but could not get it. That is why he now wants to pre-position it. See below my e-mail to Tom Frieden sent to him on Sunday, August 31 while he was in Liberia: Tom: I am including a few attachments: 1) 2 slides (from Nancy Sullivan who does our pre-clinical Ebola studies) that summarize the issue of "cytokine dysregulation" in Ebola disease and potentially following vaccination; 2) 2 reprints (referred to in the 2 slides) on the types of cytokine responses in Ebola disease and following vaccination with different vaccine platforms; and 3) the Heinz Feldmann paper with which you are familiar and which shows that in the monkey model of Ebola virus disease, the VSV Ebola vaccine used as post exposure prophylaxis (PEP) protected 50% of the monkeys from lethal challenge with Ebola if administered 20-30 minutes following the challenge. Getting back to our discussion and your question concerning the issue of any risk of administering VSV as PEP, I certainly would not characterize the inflammation following VSV vaccine administration as "cytokine storm". It certainly induces inflammation and can cause fever. Note that the only human to my knowledge who received this vaccine was the laboratory worker in Germany who had a needle stick injury and she got a fever following vaccination. Inflammation that results in fever will virtually always induce secretion of cytokines of various sorts. Since VSV in the NewLink vaccine is a replicating virus, it will almost certainly induce the secretion of cytokines. The reason that this might be important is that a whole array of cytokines are important in the pathogenesis of Ebola virus disease. It certainly can kill you (advanced cytokine storm) and it is almost certainly involved in protection and recovery from Ebola infection. It is a delicate balance that we do not fully understand. At this time, we are unclear about the positive versus negative effects of cytokine secretion (or call it dysregulation) related to the precise cytokines in question and the timing of their secretion vis-à-vis Ebola infection (see first bullet in the first of 2 slides in the first attachment. In my mind, this does not mean that one should not provide VSV as PEP for your people (or others); however, if administered to them, it should be made clear to the recipients that 1) VSV Ebola vaccine provided 50% protection in monkeys if given 20-30 minutes following exposure. I would mention that monkey models are somewhat different from human Ebola (see 3rd and 4th bullet of 2nd slide in first attachment) and so direct extrapolation to humans should be made with caution at this point in time; and 2) importantly, the vaccine recipients should clearly understand that there is a theoretical possibility that the VSV, due to the complexities of the cytokine dysregulation that accompanies Ebola infection and the perturbation of this cytokine network that might occur with a live virus vaccine (VSV) that induces inflammation and fever, might actually cause them harm by disturbing their normal inflammatory/immune response to Ebola infection. If they understand these caveats, then it would be their choice to receive the vaccine with informed consent. Finally, as you certainly know better than anyone, the FDA will have to be involved in the approval of allowing this pre-positioning and potential use of an experimental vaccine by whatever is the appropriate regulatory mechanism. I hope that this information is helpful to you in your deliberations about PEP. I look forward to discussing these issues with you. Best regards, Tony -----Original Message-----
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Sept. 1, 2014 - Labor Day - had usual call with Secretary Burwell (SMB) this AM at 8:30 AM. Clear and muggy day. We are going around in circles. I am concerned that the Secretary is a really smart and very competent person, but she is surrounded by people who may be good at management, but who have never been in a situation like this and who really do not have a clue how to address it → Leslie Dach (formerly of Walmart); Andrea Palm (have no idea where she came from). Bill Corr (Deputy Secretary) is the only one with corporate memory of former crises and he has been completely marginalized by the new kids in town. There really is no command and control at a higher level. At my suggestion, Francis sent a note to SMB suggesting that we bump this up to the White House level (perhaps the VP) in order to get DoD, USAID, HHS, and NSC working together. She has not yet responded to him. I mentioned on the call today that Tom Frieden is dealing with Assistant Secretary Lumpkin of DoD. He is a good person, but nothing is happening with the promise for mobile hospital beds. They are still quibbling about a 25 bed hospital when they really need 1000 beds. Plans for 5 X 100 beds have gone nowhere. My experience with the DoD is that they are well-meaning, but the culture and chain-ofcommand is such that you never know when you are speaking with someone who really has the authority to actually do what they are talking about. Something strange about the military culture in that they will never say "you are speaking to the wrong person; I cannot help you". They will try to help (although they cannot) and all that happens is that time is wasted. I tried to make that point on the conference call. Importantly, WHO is saying that the epidemic could reach 20,000 cases. In fact, mathematical models that came out in ScienceInsider today from a physicist named Alessandro Vespignani showed that the curve is exponential, not linear, which means that there could be 10,000 cases by September 24. This is turning into a total catastrophe. Just spoke with Dawn O'Connell (Counsellor to SMB) and explained to her that the situation is out of control and that we need a higher command and control. I also explained to her the importance of the "exponential" curve of the epidemic. Dawn is really trying to be helpful.
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Sept. 2, 2014 - Tom Frieden back from West Africa, gives press conference and says that the situation is out of control and could result in 100,000 cases! HHS people concerned that he is being hyperbolic; I do not think that he is hyperbolic. Worrisome things - an American missionary M.D. got infected while got infected in Liberia in a hospital that was not for Ebola patients. Turns out he was doing an OB-GYN exam on a woman who was infected, but did not know it and did not tell the missionary that she had been exposed. Big problem - people are not telling the truth for fear of stigma. Epidemiological curves are now exponential. A lot of planning, but not much action. I am supporting Tom in the press and at HHS even though he still thinks that we should pre=position TKM drug (siRNA) and VSV vaccine for PEP for health workers in the ETUs even though they have not been in Phase 1 yet. Did Panel at CSIS on 1616 Rhode Island Avenue. Very hot muggy day. Panel on Global Health issues in the context of Larry Gostin's new Book of Global Health Law. Panel was me, Larry and Tim Evans of World Bank. Ebola was a major topic. Important - Secretary Sylvia Burwell called my cell phone at 2:30 PM to ask my opinion of whether we were not doing enough or were doing it wrong. I told her that quantitatively we are not doing enough. But as the epidemic grows exponentially, then the quantitative defect transforms into a qualitative defect and then we are doing it wrong since doing the same thing minimally while the epidemic grows, then becomes doing it wrong. She also tasked me to find out whether there are options to improve the tobacco plant yield of the ZMapp antibodies or as suggested by some, that we go to CHO cells. She wanted me to contact the Agriculture people at the BMGF where she used to work to get their opinion. I called and spoke with Susan Hellmann (President of BMGF), Chris Elias (BMGF), Rob Horsch (Ag expert at BMGF), Larry Zeitlin (CEO of Mapp Biopharmaceutical to get their opinion. Consensus is that it will take too long to fix the poor yield in tobacco and that we should go for CHO in 2 of the 3 antibodies. The 3rd does not do well in CHO and so stick with tobacco on that one. I wrote a long e-mail to Sylvia explaining this. Press - CNN with Erin Burnett News still dominated by ISIS who beheaded another USA journalist; Russia invading eastern Ukraine; Gaza and Ebola