l. CDC MMWR 15 May has a report by Nyenswah, et. al. from the Ministry of Health, Liberia, and WHO and CDC about the last cluster of EBOV cases in Liberia last January. Most interesting fact to me was the large number of contacts (745 persons) was established by the lack of immediate EBOV diagnostics at health care clinics in Liberia. Thus, the index case spread EBOV to her family and friends who in turn by hiding themselves or crossing borders or refusing to seek help spread EBOV widely. The immediate EBOV paper tests need to be widely available for the case count in West Africa to go to zero. See the report at: http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6418a5.htm?s_cid=mm6418a5_e
2. A disturbing report re: Phase 3 vaccine trials in West Africa appears in The Lancet 12 May under World Report. The author reports on conflict between NIH and WHO because of a shortage of EBOV patients in Liberia. NIH has a Phase 3 vaccine trial going on in Liberia and wishes to move the trial to Guinea where more EBOV patients are located. Problem is that WHO is conducting its own Phase 3 vaccine trials in Guinea and says that moving the NIH trial to Guinea from Liberia will confound both trials. See: http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(15)60938-2/fulltext?elsca1=etoc&elsca2=email&elsca3=0140-6736_20150516_385_9981_&elsca4=Public%20Health%7CInfectious%20Diseases%7CHealth%20Policy%7CInternal%2FFamily%20Medicine%7CGeneral%20Surgery%7CLancet
3. WHO World Health Assembly will meet in Geneva on 18 May. Dr. Chan will present her agenda for WHO for the near future. This agenda will include: a call for member countries to make good on their mandatory and voluntary contributions to WHO; full funding for a Rapid Response Team for emerging pathogens; recognition of WHO’s new ‘job description’ going beyond ‘coordination’ between member countries. See the WHO announcement at: http://www.who.int/en/ Note that the announcement provides a means to get daily updates from WHO on the World Health Assembly. Nature 13 May has a summary of what they think will be discussed at the 18 May meeting: http://www.nature.com/news/ebola-failures-prompt-who-rethink-1.17528?WT.ec_id=NEWS-20150514. (I’d like to see ‘universal’ flu vaccine put on the agenda and ramped up. See: http://www.sciencemag.org/site/special/h5n1/index.xhtml)
4. PLoS One has an article by Barlow, et. al. from the University of California at Merced re: how to cycle antibiotics to reduce antibiotic resistance to commonly used hospital antibiotics. The authors used a mathematical formula to determine how to best cycle antibiotics. See: http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0122283
5. For those readers like me who do not have a strong math background, an explanatory summary of the PLoS One article appears in Laboratory Equipment at: http://www.laboratoryequipment.com/news/2015/05/researchers-reverse-antibiotic-resistance.
Today’s Ebola Update focuses on The Lancet 9 May issue received online in my Inbox this morning. This issue has a Public Policy Forum by Professor Heymann from the London School of Hygiene and Tropical Medicine on the Lessons Learned from the EBOV epidemic; two Viewpoints by other EBOV authorities on Lessons Learned; and a Comment by The Lancet editors:
1. Professor Heymann’s Public Policy Forum includes many world wide infection and epidemiology experts as participants. The Forum is a very lengthy article which presents so much information and so many recommendations that I refer you to two graphics within the Forum: Key Messages and Mock Dashboard for Health Services Agenda. These two graphics summarize the Forum nicely. Heymann, et. al. conclude that the world needs to do more now to prepare for the future and that African countries need to be self-reliant when it comes to the health of their populations. (RGL: The world has moved on to the next health crises in the Middle East). See the entire Forum at:
2. Kruk, et. al. from the Harvard School of Public Health in a Viewpoint identify the type of health system that all countries contending with the threat of emerging infectious diseases need to have in place. The health systems need to be aware of what’s coming down the road; diverse in composition; self-regulating-must depend upon itself-not the international community; integrative; and adaptive. These characteristics are the same characteristics that military forces strive to have. See the Kruk, et. al. article at: http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(15)60755-3/fulltext
3. Professor Heymann, et. al. have a second Lancet Viewpoint re: how to avoid being behind the curve with vaccine development for emerging pathogens. He recommends:
“Serious consideration should also be given to the creation of an internationally supported facility dedicated to rapidly developing vaccines against known emerging pathogens, such as a multivalent Filovirus vaccine that could protect against multiple Ebola virus strains and the Marburg virus.”
The authors have other recommendations as well. See: http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(15)60645-6/abstract
4. Horton, et. al., editors of the Lancet, have a Comment which nicely summarizes the Heymann, et. al. and Kruk, et. al. articles in general terms. But Horton, et. al. are way off base in declaring:
“It is, sadly, also deeply hostile to WHO, which, one senior US State Department official told us recently, has been “overwhelmed” by Ebola. The US Government remains fully committed to global health. But another government adviser tells us that the US administration is “furious” about the way existing international health arrangements failed to contain the Ebola outbreak. The USA will now “go it alone”, he said. It will protect its homeland through bilateral responses, such as the announcement of an African Centres for Disease Control and Prevention through a partnership with the African Union, not WHO. The USA will no longer be interested in UN, let alone WHO, reform, he suggests. Instead, it will do what it needs to do to protect its own interests—domestically and overseas.”
Horton, et. al. have two un-named sources and no corroborating evidence from official HHS documents or speeches that what the un-named sources said is anything more than hearsay. The editor has shown very poor editorial judgment in including this ‘slam’ against the U.S. and President Obama in his Comment. The U.S. remains committed to the WHO and UN. Whatever deficiencies are present at WHO and the UN would quickly be remedied if the member nations made good on their voluntary contributions to WHO and UN. Remember that WHO is funded >50% now by Bill Gates, Paul Allen, and their friends. I believe the Lancet should do a Erratum of this Comment and apologize to its readers.
See the entire Comment at: http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(15)60909-6/fulltext
l. Nature 23 April has and Editorial re: the newly set up pan-continental African Centres for Disease Control and Prevention (ACDC). This organization established by the African Union (AU) will not be modeled after the U.S. CDC, but after the European Center for Disease Prevention and Control (ECDC). The U.S. CDC is massive in budget and staff and has in-house laboratories; the ECDC has no in-house labs, small staff and budget, and acts as coordinator of research labs and national health bodies in the event of an infectious epidemic. The ACDC will have a small budget and only 11 staff members (including 5 epidemiologists). Yet the ACDC is supposed to prevent and treat epidemics and strengthen health systems and do national risk assessments. Experts say the ACDC needs 40x it current budget and 6x its current staff to do these tasks. The AU will need to find the money to make the ACDC a success. (RGL: The U.S. Congress funded HHS with much more money than needed to prevent and treat EBOV in the U.S; ACDC would be a good recipient for some of that money.) See the Nature editorial at: http://www.nature.com/news/highway-to-health-1.17362.
2. NPR News May 1st reports on a CDC warning that condoms should be used for all sex with a male EBOV survivor. The EBOV lasts longer than thought in semen of male survivors. See: http://www.npr.org/blogs/goatsandsoda/2015/05/01/403600464/a-man-said-to-be-ebola-free-could-still-infect-a-partner-during-sex
3. PLoS Pathogens 30 April has posted a review article by Moller-Tank, et. al. from the Gene Therapy Center at University of North Carolina on the entry of EBOV into host cells. The diagrams are well described and make most of the article useful to a non-viral researcher. Here is the legend for Figure 3:
Fig 3. Steps of Ebola Virus Entry.
(A) Cell surface receptors bind EBOV particles through interactions with either virion-associated phosphatidylserine or viral glycoprotein glycans. (B) Virus is internalized through ruffling of the plasma membrane and macropinocytosis. (C) During trafficking through endosomes, the EBOV glycoprotein is cleaved by proteases that remove the mucin-like domain (MLD) and glycan cap, exposing the receptor binding domain (RBD). Shown is a stepwise removal of those sequences, although in the cell these cleavage events may occur concurrently. (D) The RBD interacts with NPC1 in the late endosome/lysosome. (E) Binding of the NPC1 C-loop by the glycoprotein is followed by one or more triggers that release the fusion loop, allowing for its insertion into the target membrane. Subsequent transition of the EBOV GP into a six helix bundle results in the host and viral membranes being brought together, leading to fusion. (F) Release of the viral nucleoprotein into the cytoplasm prior to the initiation of virus replication.
4. Nature 29 April has a report on the fate of science in Tunisia, Egypt, and Syria since the Arab Spring. Tunisia has fared much better than the other two countries. Obtaining materials and international collaboration is a major problem for young scientists in all these countries. See: http://www.nature.com/news/science-in-turmoil-after-the-arab-spring-1.17428?WT.ec_id=NATURE-20150430
5. Nature 29 April has an interview with a Hong Kong researcher on the situation for science in Hong Kong compared to mainland China. See: http://www.nature.com/nature/journal/v520/n7549_supp/full/520S37a.html?WT.ec_id=NATURE-20150430
l. PLoS Pathogens 23 April has an article online by Casadevall, et. al. from Johns Hopkins University discussing the role of passive serum therapy in rare diseases such as EBOVand for diseases in which broad spectrum antibiotics produce severe side effects such as C. difficile infections. Serum therapy has the benefit of being specific against a single infectious agent, not broad spectrum. Side effects such as serum sickness are not common now because the serum is produced in survivors of a disease rather than horses injected with the disease. The financial gain for vendors with passive serum therapy is small because the serum is so specific. Making a ‘serum cocktail’ for multiple viral diseases is costly. See the report at: http://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1004717
2. PLoS Neglected Tropical Diseases 17 April posted online an article by Richards, et. al. from Njala University in Sierra Leone on the social network in Sierra Leone that contributes to the rapid spread of EBOV infection in rural villages. These rural villages have patrilineal ‘rule’. Trust is highest in the village leaders, and least in the government. Contact with the government can take up to 2-3 weeks because of the poor road system outside cities. There is frequent travel between villages because of uncles and aunts families in other villages. The authors discuss the need for ‘triage points’ located between cities and rural villages so that point of care diagnostic tests can be given; health care workers dispatched to villages rapidly for isolation/treatment; and some awareness of help nearby is known to the villagers and tribal leaders before disease strikes villages. See the article at: http://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0003567
3. The Lancet Infectious Disease 23 April has an Article by Walker, et. al. from Imperial College, London, estimating mathematically the number of cases of malaria generated by the 2014 EBOV epidemic if no treatment or netting or immunizations were given during the EBOV epidemic. The mathematical model predicts 3.5 million malaria cases and 10,700 deaths. These are staggering numbers (as is the 180,000 maternal deaths expected by lack of pre, peri, and post natal care due to the EBOV epidemic). See the Article at: http://www.thelancet.com/journals/laninf/article/PIIS1473-3099(15)70124-6/fulltext
4. The Lancet Infectious Disease 21 April has an article by Clark, et. al. from the Walter Reed Institute of Research, on the long term effects of EBOV infection. The authors surveyed survivors of the 2007 Ugandan outbreak. Two years after surviving infection a statistically significant number of survivors had eye problems (mostly blurring), hearing loss, loss of taste and confusion. See the article Abstract at: http://www.thelancet.com/journals/laninf/article/PIIS1473-3099(15)70152-0/abstract
5. PLoS Currents Outbreaks today posted online an article by Majumber, et. al. from MIT on the effects of positive or negative media reports on the reproductive number (R0) of the EBOV epidemic in West Africa. Postive media reports were reports that educated readers on how to avoid infection; negative reports were reports that emphasized how sick the infected patients became and described in detail how they contracted the infection (‘if it bleeds, it leads’ philosophy). Positive media reports resulted in a rapid decrease in R0, and negative media reports resulted in an increased R0. Social media directly affects R0 for EBOV infection. See the article at: http://currents.plos.org/outbreaks/article/2014-ebola-outbreak-media-events-track-changes-in-observed-reproductive-number/
l. MMWR from the CDC on April 17th reports on sudden increase in cases of EBOV in Guinea between the second and third weeks of December, 2014. The caseload went from one case to 62 cases between those weeks. All infected patients had attended a traditional burial where they all touched or kissed the body of the deceased or a close family member who cared for deceased. See the detailed MMWR report at: http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6414a4.htm?s_cid=mm6414a4_e. Education about how EBOV is spread has been increased in Guinea since this outbreak.
2. The Lancet, February, 2015, has Correspondence by Drain of Partners.org explaining how the lessons learned in HIV and TB epidemics apply to EBOV in West Africa. Specifically, a point of care diagnostic test is needed for all these epidemics; the stigma of any of these diseases must be removed so possibly infected persons identify themselves; contact tracing must be a first-order priority; and health care workers must be protected from infection. See the Drain Correspondence at: http://www.thelancet.com/journals/laninf/article/PIIS1473-3099(14)71079-5/fulltext
3. The Lancet, May, 2015, has Correspondence from Althaus of Switzerland re: how a countrywide RO may 1.0 or less, but a single ‘superinfecting’ EBOV patient may start an outbreak on his/her own. The author uses mathematics to prove his point. ‘Superinfecting’ EBOV patients are the reason that ‘getting to zero’ is so important and yet so difficult. These superinfecting EBOV patients may be in rural villages where there is no point of care diagnostic tests and where it takes days for health officers to be notified of a possible EBOV case. See the Althaus Correspondence at: http://www.thelancet.com/journals/laninf/article/PIIS1473-3099(15)70135-0/fulltext?elsca1=etoc&elsca2=email&elsca3=1473-3099_201505_15_5_&elsca4=Public%20Health%7CInfectious%20Diseases%7CInternal%2FFamily%20Medicine%7CNeuropsychiatry%7CNeurology%7CLancet
4. ACAPS today issued an report on how surveys of EBOV cases have been conducted in Sierra Leone and Liberia over the past year. Most of the surveys of a given area or region are single surveys. Multiple surveys of a given area or region is not typical. Some areas in Sierra Leone and Liberia have not been surveyed. Most of the surveys conducted in Liberia have been done by the Liberian government and have been delayed in release, so the Liberian data is suspect. ACAPS plans to get surveys done in un-surveyed areas and regions of Sierra Leone and Liberia. See: http://acaps.org/img/documents/t-acaps_mapping_assessments_-identifying_gaps_22_april_2015.pdf
5. The Paul G. Allen Family Foundation is currently holding an Ebola Innovation Summit in San Francisco to brainstorm on how to incorporate new diagnostics, new vaccines, better communication into the world’s response to the West African EBOV epidemic. Mr. Allen, who has donated $100 Million to ending the epidemic, is taking the next step-action-and he is following the recommendations of Bill Gates’ article in the NEJM. See what the Ebola Innovation Summit is brainstorming about at: http://www.pgafamilyfoundation.org/programs/ebola/key-initiatives/ebola-innovation-summit#Groups.
6. Science, 17 April, has a two page article on ‘broad spectrum’ viral drugs that are ‘One drug, multiple bugs’. Here is the Abstract of the article on page 282-283: http://www.sciencemag.org/content/348/6232/282.summary. (Science website does not recognize my password tonight). The article mentions several anti-virals I have not heard of previously.
l. The Economist has posted the latest statistics on EBOV cases and deaths to April 5th. The graphic shows by African country EBOV cases and deaths. See: http://www.economist.com/blogs/graphicdetail/2015/04/ebola-graphics
2. NEJM has two articles online April 1st re: the safety and efficacy of rVSV ZEBOV vaccine (Canada and NewLink) in Africa, Europe, and the United States. Separate trials have shown the vaccine is safe, produces fever and arthritis which is self-limited in 10-30% of volunteers, and elicits an immunogenic response with a single dose. See these two studies at: http://www.nejm.org/doi/full/10.1056/NEJMoa1502924#t=article and http://www.nejm.org/doi/full/10.1056/NEJMoa1414216#t=article
3. The Lancet has published in the journal on April 11th an article by Wolf, et. al. of University Hospital, Frankfurt, detailing the course and treatment of the Ugandan doctor who became infected with EBOV in Sierra Leone and was airlifted to Frankfurt, Germany, for intensive treatment after initiating self-treatment with amiodarone and IV fluids. This article appeared online December 19th, but is posted again because I learned much more from reading the print version than the online version. The patient received a small peptide called FX06 for his vascular leak syndrome, and the authors believe this peptide was effective against the syndrome. But the patient was receiving other experimental drugs and mechanical ventilation, renal dialysis, and blood replacement simultaneously, as an accompanying editorial notes. See the Wolf, et. al. article at: http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(14)62384-9/fulltext and the accompanying editorial at: http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(14)62353-9/fulltext
4. The Lancet article by Wolf, et. al. above gives readers ‘pearls’ on how to intubate EBOV patients, how to safely take chest radiographs, how to safely handle suction fluids and expectorated material, how to and how not to estimate left ventricular end diastolic pressure. The article is a real hands-on guide for clinicians caring for patients in Biosafety Level 4 facilities.
5. mBio has published online a report by Kugelman, et. al. from Fort Detrick stating that mutations to binding sites on EBOV for monoclonal antibodies do occur over time in human-to-human transmission of the disease. So it is important to continually sequence EBOV over time to determine if antibody-binding sites can still bind mAb directed against EBOV. See: http://mbio.asm.org/content/6/1/e02227-14.full?sid=c8be238a-e184-4b2b-8350-428e4aa39e88
6. Washington University in St. Louis Record reports that scientists at the medical school have discovered a means of preventing the protective coat surrounding the EBOV virus from being ‘reattached’ after the coat is removed in the host cell for viral replication. The original paper in Cell Reports is cited. See the Record summary at: https://news.wustl.edu/news/Pages/New-Ebola-study-points-to-potential-drug-target.aspx
7. The Lancet regularly has Correspondence urging that critical care measures be available for all EBOV patients. These measures include mechanical ventilation, renal dialysis, and chest compressions in the event of an arrest. The Lancet believes that treatments available in England and Germany should be made available to African countries as well. See one particular Correspondence at: http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(15)60712-7/fulltext?elsca1=etoc&elsca2=email&elsca3=0140-6736_20150411_385_9976_&elsca4=Public%20Health%7CInfectious%20Diseases%7CHealth%20Policy%7CInternal%2FFamily%20Medicine%7CGeneral%20Surgery%7CLancet
l. Tonight’s posting begins with a antibiotic resistance article that has important implications. Washington University in St. Louis Newsroom March 25 has a review of a June Emerging Infectious Disease article by Dantas, et. al. about antibiotic resistance of Enterobacteriaceae strains in the Americas and in South Asia. The bacterial genes producing antibiotic resistance in these strains are different (KPC in the Americas; NDM-1 in South Asia), but some plasmids carrying both KPC and NDM-1 are nearly identical in both strains and can cross into both strains, spreading antibiotic resistance. The authors state:
“The researchers also sequenced a special portion of bacterial genetic material called plasmids. Most of a bacteria’s DNA is found in its chromosome, but bacteria also have many extra, smaller and circular bits of DNA known as plasmids that easily can pass from one bacterial strain to another. A plasmid is like a bacterial gene delivery truck; it is the primary way antibiotic resistance genes spread between bacteria.
The researchers identified a few key instances in which the plasmids carrying NDM-1 or KPC were nearly identical, meaning they easily could facilitate the spread of antibiotic resistance between disease-causing bacteria found in the United States and South Asia. Recent evidence suggests that this intermingling already may be happening in parts of China.”
See the Newsroom report at: https://news.wustl.edu/news/Pages/Common-bacteria-on-verge-of-becoming-antibiotic-resistant-superbugs.aspx
2. The U.S. Department of Health and Human Services (HHS) has contracted with BioCryst for $12 Million toward development/testing of a small molecule called BCX4430 which has shown activity against EBOV and Marburg virus in non-primate animal models. See the HHS release at: http://www.hhs.gov/news/press/2015pres/03/20150331a.html
3. NEJM April 1 published an article by Regules, et. al. from Walter Reed Army Institute of Research on the safety of a new attenuated, replication-competent recombinant VSV vaccine candidate called rVSV-ZEBOV which replaces the glycoprotein of VSV with the glycoprotein of EBOV Zaire strain. No serious side-effects were reported on Phase 1 testing and the vaccine candidate is active against EBOV so Phase 2/3 testing is underway in Liberia. See the NEJM article at: http://www.nejm.org/doi/full/10.1056/NEJMoa1414216#t=article. See the NIH news release at: http://www.nih.gov/news/health/apr2015/niaid-01.htm
4. Ebola Deeply’s Executive Summary April 2 reports breakdowns in safety precautions at two EBOV treatment centers in Guinea, resulting in new EBOV cases, including 3 infected doctors. These two EBOV treatment centers have been closed down by the U.N. The 3 day quarantine of residents in Sierra Leone has identified 10 new EBOV cases, compared with 100 EBOV cases identified with the previous quarantine. See: http://www.eboladeeply.org/articles/2015/04/7666/ebola-executive-summary-april-2-2015/
5. The CDC’s MMWR report April 3 gives a detailed accounting of the steps taken to prevent NYC residents and Bellevue Hospital employees from EBOV infection via Dr. Craig Spencer after he became symptomatic in NYC and had to be transported to Bellevue Hospital for treatment. Data management of contact tracing required 12 full time staff alone; the overall cost of Spencer’s hospitalization is estimated at $4.3 Million. See this revealing report at: http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6412a3.htm?s_cid=mm6412a3_e
6. ACAPS has published a 12 page report on the status of EBOV in West Africa as of March, 2015. The indirect effects of the EBOV epidemic are being felt as the region enters the rainy season. Vaccinations for measles and pertussis are down; pre-natal visits are down; malaria cases are not coming to clinic; food supplies are short because harvests severely limited by EBOV epidemic. See: http://www.acaps.org/img/documents/m-acaps-monthly-overview-ebola-west-africa-2-april-2015.pdf
7. Lancet 24 March published a report by Zhu, et. al. from Beijing Institute of Biotechnology re: another EBOV vaccine candidate. This candidate is replication-deficient adenovirus which has its glycoprotein replaced by the glycoprotein from the 2014 Sierra Leone EBOV strain (not the much earlier Zaire EBOV strain). Safety and efficacy were proven in a study involving 80 high dose + low dose participants. See: http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(15)60553-0/fulltext