A single line often inverts meaning once you see what it
answers, so neighbouring messages are always shown.
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August 16-19, 2014 - Media blitz stopped, but the epidemic still rages. The West African countries are instituting quarantines and border closings, which may slow down the epidemic, but there is the beginning of a humanitarian crisis to get food, water and supplies to the quarantined areas. Tom Frieden and I are working out how we can reconcile the issue discussed above about the balance of open access of vaccine following phase 1 versus the need to know by RCT whether the vaccine actually works and whether it might actually do harm, as per the Ad5 HIV vaccine enhancement of HIV acquisition in a former clinical trial a couple of years ago. The department was clearly concerned (Andrea Palm - chief-of-staff to Burwell- pissed me off on a conference call by acting annoyed with Tom and me in our discussions on the daily conference call) about the disagreement between Tom and me; however, Tom and I are now trying hard to work it out behind the scenes.
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August 20, 2014 - Ebola still on an upswing. No explosion yet in Nigeria following the infection of cluster (8 to 11) health care workers who took care of (Liberian/American) who flew from Liberia to Nigeria). Tom Frieden and I still trying to work out an agreement/compromise regarding the distribution of Ebola vaccine (RCT versus expanded access) following the Pahe 1 trials that will begin in September and have data by November on Safety and immunogenicity. ral News Radio; Canadian TV; VOA TV bs; BBC Newsday d; WNEW Press low level but consistent. For me → Federal News Radio; Canadian TV; VOA TV - "Straight Talk Africa Show - 1 hour); ISIS (Islamic State in Iraq and Syria) taking over parts of Iraq Gaza still a mess with rocketing of Israel and retaliatory air strikes by Israel.
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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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2014-08-23 00:00
Anthony S. Fauci
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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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-----