Archive for November 2014
Dear Colleagues: This past Thursday through Sunday is the Thanksgiving Holiday in the U.S. Most journals, science magazines, media sources have given their staffers the 4 day holiday off work. But some EBOV news is still available:
l. Gregg Zoroya of USA Today is based currently in Monrovia, Liberia. Zoroya reports yesterday that Liberians wish to take the ’emergency’ sense of EBOV behind them. People are less diligent in avoiding handshaking and bodily contact in the cities. Rural vilagers are suspicious of Red Cross ambulances coming to take deceased EBOV patients away for cremation. I think it is time for the Red Cross to remove their insignia from their ambulances so that villagers do not hide bodies from the teams traveling to villages to remove bodies.
2. The Lancet 19 November published correspondence critical of the Canadian government for its sale of rights to VSV-ZEBOV to NewLink because NewLink had not developed, tested, or distributed the vaccine for use in the several years ZEBOV held its rights. Fortunately, subsequent to 19 November NewLink sold the rights to VSV-ZEBOV to Merck so that the vaccine can be ‘scaled up’. NewLink’s action was a humanitarian action as previously noted. To protect the public, I believe a ‘compassionate use’ clause should be included in any governmental contract selling rights to vaccines or drugs to private corporations. See The Lancet correspondence at: http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(14)62044-4/fulltext
3. Science 21 November has an article describing the decision process undertaken by physicians/patient at Nebraska Medical Center when deciding which experimental drug the patient (Ashoka Mukpo) should be given at the Center. Note that Mukpo’s father is a pulmonologist and was a member of the decision team. The final decision was to use convalescent serum and brincidpfovir, which has a substantial safety record. TKM-Ebola was not given because of worries it could trigger overproduction of cytokines. See more about the decision process and a chart of experimental drugs under development at: http://www.sciencemag.org/content/346/6212/908.full
4. CDC has released an updated FAQ report on the successfully tested chimpanzee adenovirus Type 3 vaccine. See the report at: http://www.niaid.nih.gov/news/QA/Pages/EbolaVaxResultsQA.aspx
5. Dr. Racaniello has posted a short article on how ZMapp antibodies work against EBOV on his Microbe TV website. See the article at: http://www.virology.ws/2014/11/25/how-zmapp-antibodies-bind-to-ebola-virus/
6. West African countries with EBOV have one other common factor I did not include in my previous blog: all these countries are producers of cocoa. These countries are not the major producers but cocoa trees are indigenous. Cocoa trees have fruit called cocoa pods. Within these cocoa pods is a gelatinous mass which contains cocoa beans which are pressed and process to make chocolate. Ten-twelve cocoa pods produce a pound of chocolate.
.7. Fruit bats eat the cocoa pod leaving EBOV containing saliva on the pods; these fruit bats are also responsible for carrying pollen from one pod to another. Villagers then harvest the pods and split them to obtain the cocoa seeds spreading fruit bat saliva on their hands and food and anything they touch. See a more detailed discussion of fruit bats and cocoa trees at: http://www.melissa-stewart.com/images/pdfs/nmnc/mss_whomakes.pdf?lightbox%5Biframe%5D=true&lightbox%5Bwidth%5D=800&lightbox%5Bheight%5D=500
I will be on the road tomorrow Sunday and will post next on Monday evening.
l. NEJM published on-line only tonight two articles on safety/immunogenics of a chimpanzee adenovirus Type 3 vaccine (cAd3-EBO) encoding the glycoprotein (GP) from Zaire and Sudan species of EBOV (note vaccine is bivalent because it encodes GP of two species). The Original Article by Ledgerwood, et. al. tested cAd3-EBO at two different doses in two groups of 10 patients. The vaccine was safe at both doses and delivered immunogenicity at both dose (higher dose provided more immunogenicity). See the Ledgerwood, et. al article at: http://www.nejm.org/doi/full/10.1056/NEJMoa1410863?query=featured_ebola#t=articleTop.
2. An accompanying NEJM Editorial by Bausch at Tulane University notes that the cAd3-EBO vaccine produces both humoral and cell-mediated immune responses and that the higher dose vaccine produced 70% more CD8 T-cell response than the lower dose vaccine. One high fever/low white count developed in the high dose vaccine test group. Brausch’s Editorial in Paragraph 3 lists the practical questions which need to be answered in further human tests on this vaccine. See the Editorial at: http://www.nejm.org/doi/full/10.1056/NEJMe1414305?query=TOC
4. The open source journal Viruses has a Special Issue related to the Filoviruses. A Letter within this Special Issue by Kuhn, et. al. entitled ‘Filovirus RefSeq Entries…’ has a Figure 1 which nicely depicts the differences betwee Ebola and Marburg and the differences between the Ebola species by genomic differences. For non-virologists like myself, Figure 1 is much easier to understand than phylogenetic trees. See the Kuhn, et. al. Letter and Figure 1 at: http://www.mdpi.com/journal/viruses/special_issues/filovirus_2014_2015.
5. ACAPS Global Emergency Review 25 November shows the distribution of Severe Humanitarian Crises in the world. Most of these severe crises are located in West and Central Africa-the same locations as the EBOV epidemic. When I reviewed the environmental charts of these African countries in ‘Atlas of Africa’ by Campbell, Porter, Lye, the countries have the following in common: tropical rainforests, rainforests seriously damaged in recent years, and the intersection of Muslim, Christian, and Traditional religions in Africa. See the ACAPS review at: http://geo.acaps.org/
6. PLoS Computational Biology published on-line 13 November an article by Generous, et.al. from Los Alamos that reports Wikipedia can be used to accurately monitor and forecast global disease up to 28 days in advance (limit of the study). This can even be done for countries in which there is no official data. The article is complementary to a previous article that showed how mobile phone data could be used to track EBOV in Sierra Leone. See the Generous, et. al. article at: http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1003892#abstract1
I will be on the road tomorrow and may not have access to Internet connectivity, depending on the weather in the Midwest. If no Internet connection, the next blog posting will be this coming Friday.
A surreal moment at my St. Louis hospital today- a National Guard Humvee parked outside our hospital entrance to give all HCW a sense of security at work today. Guardsmen were on site, but not within view of staff or patients.
Happy Thanksgiving to Everyone,.
l. Today I learned about the ILO, the International Labor Organization, which was the first specialized agency of the U.N. in 1946. The ILO promotes social justice by promoting jobs and protecting workers. The ILO has joined with the WHO in producing protocols and educational materials on EBOV for the 158 countries which belong to the ILO. See: http://www.ilo.org/safework/areasofwork/occupational-health/WCMS_302846/lang–en/index.htm for a description of ILO activities related to EBOV.
2. News media reported today that the Chinese EBOV treatment center (100 beds) has opened in Monrovia, Liberia. This center has air-conditioning and electronic medical records. HCW in PPEs may be able to care for patients in the ‘hot zone’ for more than 1.5 hours with the air-conditioning. See: http://www.cbsnews.com/news/china-builds-ebola-treatment-center-in-liberia/ for photographs of the center.
3. WHO reports on an eighth case of EBOV in Mali today. ALL cases in this second wave of EBOV are related to contact with the grand iman from Guinea who died in Mali.
4. NPR carried a story of a reporter who traveled with a contact tracing team in Liberia to search out a possible EBOV patient in the forest. She drove for 5 hours, hiked for another 4 hours to a remote village where the sick woman lived. The woman’s hut was shut tight; villagers told the contact tracing team that she had left the village (probably at the urging of the traditional healer). The team had to turn back immediately without a search for the woman because a bridge of branches across a river might be carried away by the rising river. This is what contact tracing is like in rural Liberia. See the story at: http://www.npr.org/blogs/goatsandsoda/2014/11/24/365689595/ebola-in-remote-liberia-through-the-eyes-of-a-local-health-worker
5. Ebola Deeply reports that burial workers in Sierra Leone are leaving bodies at doorsteps instead of burying them because these workers have not received their ‘hazard pay’ from the government. This is the second time the government has not distributed the agreed upon hazard pay to burial workers.
6. CNBC reports that the $2.7 million purchase of PPEs by the CDC has produced a shortage of PPEs for West Africa. The result is an increase in the price of PPEs for West Africa (law of supply and demand). The price of a face mask has increased 30% in the last five weeks.
7. Washington Post reports that USAID has sponsored a competition for the ‘Maker Movement’ to develop innovative equipment for HCW in West Africa; e.g. air-cooled PPEs. The grants are upwards of $5 Million for winners. Some college engineering majors have developed exciting ideas. Read about these ideas at: http://www.washingtonpost.com/business/on-it/usaid-seeks-help-from-maker-movement-in-ebola-outbreak/2014/11/23/1c8d9a4a-6611-11e4-bb14-4cfea1e742d5_story.html.
8. Pentagon is testing a ‘Care Cube’ for EBOV patients so that the patient is isolated from HCW rather than the other way around. See: http://www.usatoday.com/story/nation/2014/11/25/darpa-ebola-treatment-center/70094634. DARPA is interested.
l. WHO reports that Director General Chan visited Bamako, Mali, today to meet with the Mali President and Health Minister re: the Mali EBOV outbreak. U.N. is establishing an office in Mali to coordinate response to the Mali situation. U.N. reports 500 contacts to be traced in Mali.
2. Wall Street Journal reports that Merck has purchased the rights to the NewLink vaccine for EBOV. This vaccine is the recombinant VSV-EBOV vaccine. GSK has the rights to another EBOV vaccine, and Johnson & Johnson has joined with a private firm for rights to a third vaccine. Now all 3 vaccines can be ‘scaled up’ in production and testing. NewLink’s sale of its vaccine rights to Merck is a humanitarian action in my opinion.
3. The Lancet correspondence column today has a follow-up to the article I cited about ‘natural’ immunity to EBOV in 15% of persons in Gabon who live in the forests. The correspondent refers to two articles which discuss immunity against EBOV. A very recent article by Rasmussen, et. al. found that EBOV-infected mice with one form of a gene for endothelial tyrosine kinases (Tie1 and TeK) produced plenty of tyrosine kinase and the mice survived the EBOV infection. Other EBOV-infected mice which had another form of a gene for the endothelial tyrosine kinases produced little tyrosine kinase died of the EBOV, See: http://www.sciencemag.org/content/346/6212/987.full for the Rasmussen, et. al. article.
4. The Lancet correspondent also cites an article in J Infect. Dis. by Sanchez, et.al. in 2007 in which the authors found the HLA A-B genes (Human Leukocyte Antigen A and B) had forms (B*67 and B*15) which predicted which patients with Sudan EBOV (SEBOV) died of SEBOV infection, and forms (B*07 and B*14) which predicted which patients survived the SEBOV infection. See: http://jid.oxfordjournals.org/content/196/Supplement_2/S329.full for the Sanchez article.
5. For non-scientists: HLA A-B genes work by coding for special antigens in cells; these special antigens digest viruses infecting the cells and carry ‘pieces’ of these viruses to the cell surface so killer-T cells can attack them and intact viruses. Note: Different forms of the HLA A-B genes are called alleles; for example, blood types A, B, O, etc. are different alleles of the blood gene).
Earlier this week I was told: ‘Sometimes crises are necessary for catalytic change’. Tonight is a crisis night in St. Louis; the Grand Jury verdict re: the death of Michael Brown will be delivered to the public by the County Prosecutor in 2 hours. Please pray for the safety of life, property, and constitutional rights in the aftermath of the Jury’s verdict. The Governor, County Executive, Mayor, and Police have asked for calm on TV just now, and I can hear police helicopters overhead. It is a surreal moment for me.
Dear Colleagues: Tonight is Sunday in the U.S. so that journal postings, magazine articles, and media reports on EBOV are few in number.
l. Reuters reports the U.N. has established an office in Mali to help stop the EBOV outbreak in Mali. Six deaths are now reported; one EBOV patient is under treatment. Mali says there are 300 contacts of the deceased iman and his nurse that are being followed. The U.N. says there are 500 such contacts.
2. USA Today reports the EBOV infection rate in Sierra Leone increased 30% from November 4th to November 21st. U.K. is now sending additional HCW to Sierra Leone to stem the tide. The status of cases in Guinea is unconfirmed because cases are in rural villages.
3. Gabon is not currently experiencing EBOV. Four outbreaks have occurred in the past in Gabon-1994, 1996, 1997, and 2001. Research done in Gabon in 2010 by the French Institute for Research and Development showed that 15% of the persons living in Gabon forests had antibodies to EBOV, but no history of clinical EBOV. Apes, chimpanzees, and fruit bats also live in these forests. Note only 2% of persons living in lakeland areas in Gabon had antibodies to EBOV. The IRD report is interesting reading and includes photos of the forest and lakeland areas of Gabon. See this report at: http://en.ird.fr/the-media-centre/scientific-newssheets/337-possible-natural-immunity-to-ebola
l. Tonight CSPAN (TV) presented Dr. Fauci’s formal talk and Q/A from his recent appearance at a National Press Club luncheon. Dr. Fauci was clearly more relaxed than when delivering testimony to Congress; when asked how he remains so calm in crises, he responded that he speaks about scientific facts, remains consistent in his remarks, and states when he is uncertain or does not know the answers to questions. Re: EBOV he stated that we need regional centers for EBOV and other BSL 3 and 4 infections; that the American public needs to consider the probability of EBOV infection (very low due to our health infrastructure) when discussing EBOV as a health risk; that the best means of avoiding any infection is: ‘Wash your hands’.
2. Science 14 November on page 823 reports further on TLR4, the receptor that mediates the reaction that allows ‘shed’ EBOV glycoprotein (GP) to bind to macrophages and dendritic cells and thereby release cytokines which make blood vessels ‘leaky’. See: Sci. Signal. 7, ra108 (2014).
3. WHO reported yesterday on the case number and distribution of EBOV in West Africa in a Situation Update. EBOV is still widespread in Liberia, Sierra Leone, and Guinea; over 15,000 cases and over 5,000 deaths. See: http://www.who.int/csr/disease/ebola/situation-reports/en/?m=20141121. Dr. Chan of WHO and Secretary General Ban Ki-Moon of the U.N. urged the the world not to become complacent because of the recent decrease in reported cases in Liberia and Guinea. It is not likely that the U.N.’s goal of 70% safe burials and 70% isolation of EBOV patients in West Africa will be met by the U.N.’s December 1st date. See; http://www.nytimes.com/2014/11/22/world/africa/mali-ebola-epidemic-who.html?_r=0 for more details of their webcast from the World Bank.
1. NY Times reports that 6 people, including one physician, have died of EBOV in Mali as a result of contact with the Grand Iman who traveled from Guinea to Mali with EBOV. Other sources have reported that 20,000 people attended the iman’s burial in Guinea (he was transported back to Guinea after dying) and 3,000-4,000 people touched his body at the burial ceremony.
2. The Lancet today contains Correspondence re: rebuilding health systems in West Africa vs. treatment with vaccines/experimental drugs. Both sides of the question are presented in: http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(14)62236-4/fulltext
3. WHO announced that DRC is now free of EBOV disease. It has been 42 days without a new case of EBOV. A total of 66 cases were diagnosed previously. WHO attributes DRC’s rapid response teams (mobile teams including mobile labs) with stopping the outbreak in DRC.
4. NY Times reports that EBOV epidemic in Liberia is slowing. As a result, U.S. troops will build a total of 500 beds in Liberia, not the originally planned 1700 beds. The epidemic in Sierra Leone continues to mount; the situation in Guinea is not well documented.
5. PLoS Current Outbreaks posted an article by Fisman and Tuite from University of Toronto, Ontario, Canada, re: number of vaccination doses and timing to reduce the reproductive rate of EBOV in West Africa to < 1 and stop the epidemic. The authors report that 3-4 million doses of vaccine given by January, 2015, will stop the epidemic (Re = 0.9). (Without a vaccination program the authors project the EBOV epidemic to peak in April-May, 2015). The later in 2015 the vaccinations are given, the less effect the vaccinations will have on the EBOV epidemic. There is a ‘closing window of opportunity’ with a vaccination program. See the complete article and its understandable charts/figures at: http://currents.plos.org/outbreaks/article/projected-impact-of-vaccination-timing-and-dose-availability-on-the-course-of-the-2014-west-african-ebola-epidemic/
6. PLoS Pathogens posted an article by senior author Volchkov, et. al, from the University of Lyon, France,. re: shed GP (glycoprotein) from EBOV which (unlike secreted GP) binds to macrophages and dendritic cells in an infected patient and produces release of cytokines which make vacular endothelium ‘leaky’. The TLR4 receptor is the mediator for this process, so anti-TLR 4 antibodies could prevent the cytokine release. See: http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1004509 for this article.