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To: Thud; Smokin' Joe; PA Engineer; Tilted Irish Kilt; Black Agnes; Shelayne; Covenantor; ElenaM
Oh eff-ing h*ll...

The TFMetalsreport Ebola thread here:

Ebola in CONUS (Ebola #3 thread)
http://www.tfmetalsreport.com/comment/437256#comment-437256

Reports the following:

There appear to be multiple variants of the same strain in this epidemic. Some victims are actually infected with multiple variants and therefore the clinical behavior of the epidemic varies by the predominant variant.”

Basicly, we not only need a very fast and effective Ebola test. We need one that can tell us which genetic variants are in the sample to know what the likely symptom presentation will be!

See the following science report on Ebola mutation as the related cite.


Ability to mutate
Viral dynamics during the 2014 outbreak.

(A) Mutations, one patient sample per row; beige blocks indicate identity with the Kissidougou Guinean sequence (GenBank accession KJ660346). The top row shows the type of mutation (green, synonymous; pink, nonsynonymous; gray, intergenic), with genomic locations indicated above. Cluster assignments are shown at the left. (B) Number of EVD-confirmed patients per day, colored by cluster. Arrow indicates the first appearance of the derived allele at position 10,218, distinguishing clusters 2 and 3. (C) Intrahost frequency of SNP 10,218 in all 78 patients (absent in 28 patients, polymorphic in 12, fixed in 38). (D and E) Twelve patients carrying iSNV 10,218 cluster geographically and temporally (HCW-A = unsequenced health care worker; Driver drove HCW-A from Kissi Teng to Jawie, then continued alone to Mambolo; HCW-B treated HCW-A). KGH = location of Kenema Government Hospital. (F) Substitution rates within the 2014 outbreak and between all EVD outbreaks. (G) Proportion of nonsynonymous changes observed on different time scales (green, synonymous; pink, nonsynonymous). (H) Acquisition of genetic variation over time. Fifty mutational events (short dashes) and 29 new viral lineages (long dashes) were observed (intrahost variants not included).

Patterns in observed intrahost and interhost variation provide important insight about transmission and epidemiology. Groups of patients with identical viruses or with shared intrahost variation show temporal patterns suggesting transmission links (fig. S10). One iSNV (position 10,218) shared by 12 patients is later observed as fixed within 38 patients, becoming the majority allele in the population (Fig. 4C) and defining a third Sierra Leone cluster (Fig. 4, A and D, and fig. S8). Repeated propagation at intermediate frequency suggests that transmission of multiple viral haplotypes may be common. Geographic, temporal, and epidemiological metadata support the transmission clustering inferred from genetic data (Fig. 4, D and E, and fig. S11) (6).

The observed substitution rate is roughly twice as high within the 2014 outbreak as between outbreaks (Fig. 4F). Mutations are also more frequently nonsynonymous during the outbreak (Fig. 4G). Similar findings have been seen previously (15) and are consistent with expectations from incomplete purifying selection (16–18). Determining whether individual mutations are deleterious, or even adaptive, would require functional analysis; however, the rate of nonsynonymous mutations suggests that continued progression of this epidemic could afford an opportunity for viral adaptation (Fig. 4H), underscoring the need for rapid containment.

As in every EVD outbreak, the 2014 EBOV variant carries a number of genetic changes distinct to this lineage; our data do not address whether these differences are related to the severity of the outbreak. However, the catalog of 395 mutations, including 50 fixed nonsynonymous changes with 8 at positions with high levels of conservation across ebolaviruses, provides a starting point for such studies (table S4).

To aid in relief efforts and facilitate rapid global research, we have immediately released all sequence data as it is generated. Ongoing epidemiological and genomic surveillance is imperative to identify viral determinants of transmission dynamics, monitor viral changes and adaptation, ensure accurate diagnosis, guide research on therapeutic targets, and refine public health strategies. It is our hope that this work will aid the multidisciplinary international efforts to understand and contain this expanding epidemic.

In memoriam: Tragically, five co-authors, who contributed greatly to public health and research efforts in Sierra Leone, contracted EVD and lost their battle with the disease before this manuscript could be published: Mohamed Fullah, Mbalu Fonnie, Alex Moigboi, Alice Kovoma, and S. Humarr Khan. We wish to honor their memory.

http://www.sciencemag.org/content/345/6202/1369.full

3,262 posted on 10/07/2014 2:28:26 PM PDT by Dark Wing
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To: Dark Wing

That study was posted a thousand or so comments back but it’s well worth reposting.

There are at least two variants at work in this outbreak, possibly three. That really complicated matters. I think the plethora of false negatives we’re seeing is due to that fact.


3,269 posted on 10/07/2014 3:04:06 PM PDT by ElenaM
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To: Dark Wing
Sounds like a more detailed studied of the Guinea Ebola strain that first identified it as a different clade from previous Ebola strains. That was back in April 2014.

This new bit is chilling news> The designated parrot Dr. Frieden's spin should be interesting.

Study: Growing Guinea outbreak caused by new Ebola strain

Filed Under: Ebola; VHF

Lisa Schnirring | Staff Writer | CIDRAP News |

Apr 17, 2014

http://www.cidrap.umn.edu/news-perspective/2014/04/study-growing-guinea-outbreak-caused-new-ebola-strain

The Ebola virus strain responsible for Guinea's outbreak—now at 197 suspected or confirmed cases—is a new strain that has been sickening and killing people at least as far back as December, researchers reported yesterday.

The results of full genetic sequencing suggest that the outbreak in Guinea isn't related to others that have occurred elsewhere in Africa, according to an international team that published its findings online in the New England Journal of Medicine (NEJM).

The report is also the first detailed look at the epidemiologic features among the patients sickened in the early days of the outbreak in the forested region of Guinea, sketching out transmission chains that start with a 2-year-old girl who died in December.

[section on WHO data of April 2014 deleted]

Clinical features, genetic analysis

In the NEJM report, researchers said Guinea's health ministry first learned of clusters of a highly fatal mysterious disease that had been occurring in two cities in the forested region on Mar 10. The finding triggered an epidemiologic investigation by a European team from Doctors without Borders (Medecins Sans Frontieres) and prompted the collection of blood samples and clinical data from 20 patients, which were sent to biosafety level 4 labs for analysis in Lyon, France, and Hamburg, Germany.

Fifteen of the patients tested positive for the virus using conventional filovirus tests, and electron microscopy identified the Ebola virus in the serum of one patient. Researchers isolated the virus from cell culture in samples from five patients.

The team's genetic analysis found a high degree of similarity among 15 partial and 3 full-length sequences. Meanwhile, their full-length sequence analysis revealed that the Ebola clade is separate from other known viruses of its kind.

Clinical investigation found that the most common symptoms among confirmed case-patients were fever, severe diarrhea, and vomiting, but hemorrhage was less common. The case-fatality rate (CFR) of initial cases was 86% and for suspected cases was 71%, consistent with EVD.

Three fruit bat species that are thought to harbor Ebola viruses are found in large parts of West Africa, and the first outbreak in Guinea serves as a warning that the whole West African region is at risk for the disease, the team concluded.

Evidence of single introduction

The group's look back at the transmission chains found that the first suspected case was a 2-year-old girl from Gueckedou prefecture who died in early December. They also found that an infected health worker from the same part of Guinea appears to have spread the virus to Macenta, Nzerekore, and Kissidougou in February. As the outbreak grew, 13 of the confirmed cases could be linked to four clusters.

Researchers concluded that genetic evidence and epidemiologic links between the cases suggests a single introduction of the virus from animals to humans, which could have occurred in early December or before. They wrote that they suspect the virus was transmitted for months before clusters of cases in Gueckedou and Macenta signaled that an outbreak was under way.

Hemorrhage wasn't documented for most of the patients when blood samples were obtained, but could have occurred later, the team noted. They said, however, that the term "Ebola virus disease" was developed to emphasize that hemorrhage isn't seen in all patients. The researchers said the CFR is consistent with previous Ebola outbreaks.

That the Guinea Ebola strain is a separate clade suggests that the pathogen that sparked the outbreak evolved parallel with those seen in the Democratic Republic of Congo and Gabon and was not introduced into Guinea—the first West African nation to experience an Ebola outbreak—from those countries.

3,276 posted on 10/07/2014 4:40:37 PM PDT by Covenantor ("Men are ruled...by liars who refuse them news, and by fools who cannot govern." Chesterton)
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