Archive for April 2015

Evening Ebola Update, Tues, 4/28/15: Review of serum therapy/R0 varies with tone of media reports/if EBOV prevented all malaria rx last year, then 10,000 deaths   Leave a comment

4/28/15

Dear Colleagues:

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/

RGL, MD

Posted April 29, 2015 by levittrg in Uncategorized

Evening Ebola Update, Wed, 4/22/15: Better communication needed to prevent sporadic outbreaks/’Superspreaders’/Learning from HIV, TB   Leave a comment

4/22/15

Dear Colleagues:

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.

RGL, MD

Posted April 23, 2015 by levittrg in Uncategorized

Evening Ebola Update, Wed, 4/15/15: Frankfurt case report in detail gives ‘pearls’/NewLink vaccine working/ZEBOV mutates with human-human infection   Leave a comment

4/15/15

Dear Colleagues:

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

RGL, MD

Posted April 15, 2015 by levittrg in Uncategorized

Evening Ebola Update, 4/5/15: New vaccine candidates work in small tests/Plasmids confer antibiotic resistance/Sloppy safety in Guinea closes ETCs/Rainy season effects of EBOV   Leave a comment

Easter Sunday

Dear Colleagues:

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

RGL, MD

Posted April 6, 2015 by levittrg in Uncategorized