Friday, October 10, 2014

Patient Zero




Only the third time in the past 11 years I have been sick with some kind of respiratory illness. I thought I changed my earlier blog post to indicate 11 years instead of 8 years but I didn't seem to.

I have only been sick only three times since at least the year 2003. Might have been the year 2002 the last time. Definitely not after 2003 except for the three occurrences I have tracked the dates for. The second time was just after I considered moving into an apartment named West Point and traveled there to view it. For this third time I think of it as just a cold. I don't really know the difference between a cold and the flu. I just think the flu has stronger symptoms than a cold. I didn't measure my body temperature. I was out of it for a few days. At one point I seemed to have to get up every hour to go to the bathroom because I had drank so much bottled water thinking that would help.

I remember that incident very well. I remember because I have been especially aware of sickness since I worked at Microsoft and so I was keeping track of it after I was in the VA hospital.

And so in December 2014 I remember especially well because of a comment a woman made to me when uncharacteristically I went to the supermarket late in the day on Christmas Eve. I remember thinking about it when I started feeling bad the next day. At first I thought the air quality was just bad. I was coughing and I thought the reason was the so-called ridiculously resilient ridge of High Pressure causing stagnant air and wood smoke pollution.

I haven't written about it because something just seems wrong. Something about my so-called time-traveler effect I cannot figure out. I also can't remember what the hell the light fixtures are supposed to be about. Sometimes rarely my cryptic method of recording my observations backfires and I can't remember what the hell it was I was noting.

Doesn't matter. I have established that just because I document something here in this theoretical time-traveler journal that doesn't cause anything to happen in the future.

Look at how their supposed facts are changing. Supposedly that infant in Africa got sick and died at precisely the same time I got sick for only the third time in at least 11 years.










JOURNAL ARCHIVE: - posted by H.V.O.M - Kerry Wayne Burgess 04:02 AM Pacific Time somewhere near Seattle Washington USA Saturday 28 December 2013 - http://hvom.blogspot.com/2013/12/see-its-this-kind-of-stuff-that-really.html


http://www.cswap.com/1995/Twelve_Monkeys/cap/en/25fps/a/01_54

Twelve Monkeys


1:55:23
- You don't understand.
- No, I don't have to understand.


[JOURNAL ARCHIVE 28 December 2013 excerpt ends]










http://www.nejm.org/doi/full/10.1056/NEJMoa1404505#t=article

The NEW ENGLAND JOURNAL of MEDICINE


Original Article

Brief Report

Emergence of Zaire Ebola Virus Disease in Guinea

Sylvain Baize, Ph.D., Delphine Pannetier, Ph.D., Pharm.D., Lisa Oestereich, M.Sc., Toni Rieger, Ph.D., Lamine Koivogui, Ph.D., N'Faly Magassouba, Ph.D., Barrè Soropogui, M.Sc., Mamadou Saliou Sow, M.D., Sakoba Keïta, M.D., Hilde De Clerck, M.D., Amanda Tiffany, M.P.H., Gemma Dominguez, B.Sc., Mathieu Loua, M.D., Alexis Traoré, M.D., Moussa Kolié, M.D., Emmanuel Roland Malano, M.D., Emmanuel Heleze, M.D., Anne Bocquin, M.Sc., Stephane Mély, M.Sc., Hervé Raoul, Ph.D., Valérie Caro, Ph.D., Dániel Cadar, D.V.M., Ph.D., Martin Gabriel, M.D., Meike Pahlmann, Ph.D., Dennis Tappe, M.D., Jonas Schmidt-Chanasit, M.D., Benido Impouma, M.D., Abdoul Karim Diallo, M.D., Pierre Formenty, D.V.M., M.P.H., Michel Van Herp, M.D., M.P.H., and Stephan Günther, M.D.

N Engl J Med 2014; 371:1418-1425October 9, 2014DOI: 10.1056/NEJMoa1404505

Outbreaks caused by viruses of the genera ebolavirus and marburgvirus represent a major public health issue in sub-Saharan Africa. Ebola virus disease is associated with a case fatality rate of 30 to 90%, depending on the virus species. Specific conditions in hospitals and communities in Africa facilitate the spread of the disease from human to human. Three ebolavirus species have caused large outbreaks in sub-Saharan Africa: EBOV, Sudan ebolavirus, and the recently described Bundibugyo ebolavirus.1,2 Epidemics have occurred in the Democratic Republic of Congo, Sudan, Gabon, Republic of Congo, and Uganda. Reston ebolavirus circulates in the Philippines. It has caused disease in nonhuman primates but not in humans.3 The fifth species, Tai Forest ebolavirus, was documented in a single human infection caused by contact with an infected chimpanzee from the Tai Forest in Ivory Coast.4 Although this event indicated the presence of Tai Forest ebolavirus in West Africa, this subregion was not considered to be an area in which EBOV was endemic.

On March 10, 2014, hospitals and public health services in Guéckédou and Macenta alerted the Ministry of Health of Guinea and — 2 days later — Médecins sans Frontières in Guinea about clusters of a mysterious disease characterized by fever, severe diarrhea, vomiting, and an apparent high fatality rate. (Médecins sans Frontières had been working on a malaria project in Guéckédou since 2010.) In Guéckédou, eight patients were hospitalized; three of them died, and additional deaths were reported among the families of the patients. Several deaths were reported in Macenta, including deaths among hospital staff members. A team sent by the health ministry reached the outbreak region on March 14 (Figure 1). Médecins sans Frontières in Europe was notified and sent a team, which arrived in Guéckédou on March 18. Epidemiologic investigation was initiated, and blood samples were collected and sent to the biosafety level 4 laboratories in Lyon, France, and Hamburg, Germany, for virologic analysis.

Methods

Patients

Blood samples were obtained from 20 patients who were hospitalized in Guéckédou, Macenta, and Kissidougou because of fever, diarrhea, vomiting, or hemorrhage. Demographic and clinical data for the patients were provided on the laboratory request forms. Clinical data were not collected in a systematic fashion. This work was performed as part of the public health response to contain the outbreak in Guinea; informed consent was not obtained.

Diagnostic Assays

Viral RNA was extracted from 50 to 100 μl of undiluted plasma and 1:10 diluted plasma with the use of the QIAmp viral RNA kit (Qiagen). Nucleic acid amplification tests for detection of filoviruses and arenaviruses were performed with the use of commercially available kits and published primers and probes5-11 (Table S1 in the Supplementary Appendix, available with the full text of this article at NEJM.org).

Viral Sequencing

Fragments amplified by filovirus L gene–specific primers were sequenced with the use of polymerase-chain-reaction (PCR) primers. Complete EBOV genomes were sequenced directly with the use of RNA extracted from serum obtained from three patients with high levels of viral RNA, as measured on real-time reverse-transcriptase–PCR (RT-PCR) analysis. The genome was amplified in overlapping fragments with the use of EBOV-specific primers. The fragments were sequenced from both ends with the use of conventional Sanger techniques. The sequence of the contigs was verified by visual inspection of the electropherograms.

Viral Isolation

About 100 μl of all serum samples was used to inoculate Vero E6 cells maintained in 25-cm2 flasks in Dulbecco's modified Eagle's medium containing 2 to 5% fetal-calf serum and penicillin–streptomycin. Cells and supernatant were passaged several times. Virus growth in the cells was verified on immunofluorescence with the use of polyclonal mouse anti-EBOV–specific antibodies in the serum of mice challenged with EBOV or on the basis of an increase in viral levels in the cell-culture supernatant over several orders of magnitude, as measured on real-time RT-PCR.

Electron Microscopy

Specimens from two patients were prepared for electron microscopy with the use of a conventional negative-staining procedure. In brief, a drop of 1:10 diluted serum was adsorbed to a glow-discharged carbon-coated copper grid and stained with freshly prepared 1% phosphotungstic acid (Agar Scientific). Images were taken at room temperature with the use of a Tecnai Spirit electron microscope (FEI) equipped with a LaB6 filament and operated at an acceleration voltage of 80 kV.

Phylogenetic Analysis

We obtained all 48 complete genome sequences of filoviruses that are currently available from GenBank and aligned them with the new EBOV Guinea sequences (18,959 nucleotides). We used software designed to perform statistical selection of best-fit models of nucleotide substitution (jModelTest12) to identify the general time-reversible model of sequence evolution with gamma-distributed rate variation among sites (GTR+gamma) as the model that best describes the phylogenetic data. We used the Bayesian Markov Chain Monte Carlo method, as implemented in MrBayes 3.1.2 software,13 to infer the composition of one phylogenetic tree, using two runs of four chains with 1 million steps with a burn-in rate of 25% and the GTR+gamma model. A second tree was inferred for the same alignment with a maximum-likelihood method implemented in PhyML software14 under the GTR+gamma model with 1000 bootstrap replications. A reconstruction of the EBOV phylogenetic tree with the use of molecular clock models is provided in Fig. S1 in the Supplementary Appendix.

Epidemiologic Investigations

We gathered data on possible transmission chains from hospital records and through interviews with patients in whom EBOV infection was suspected and their contacts, affected families, inhabitants of villages in which deaths occurred, attendants of funerals, public health authorities, and hospital staff members.

Results

Identification of the EBOV Strain

To detect the causative agent, we used conventional Filoviridae-specific RT-PCR assays targeting a conserved region in the L gene to test samples obtained from 20 hospitalized patients who were suspected of being infected with a hemorrhagic fever virus.5,6,9 In addition, we performed EBOV-specific real-time RT-PCR assays targeting the glycoprotein (GP) or nucleoprotein (NP) gene.7,10 Samples from 15 of 20 patients tested positive on the conventional L gene PCR assay and the real-time assays (Table 1). EBOV was identified in the serum of one patient on electron microscopy (Figure 2, inset) and was isolated in cell culture from 5 patients. None of the samples were positive for Lassa virus on Lassa virus–specific RT-PCR assays.8,11 Sequencing of the fragments amplified by the L gene RT-PCR assays revealed EBOV sequences. The partial L gene sequences were identical for all confirmed cases, except for a synonymous T-to-C polymorphism at position 13560, which was found in Patients C12 and C14.

Sequencing of Samples from Patients

The EBOV in samples obtained from three patients was completely sequenced with the use of conventional Sanger techniques (GenBank accession numbers, KJ660346, KJ660347, and KJ660348; the sequences in the preliminary report have been updated). The three sequences, each 18,959 nucleotides in length, were identical, with the exception of a few polymorphisms at positions 2124 (G→A, NP552 glycine→glutamic acid), 2185 (A→G, synonymous), 6909 (A→T, sGP291 arginine→tryptophan), 9923 (T→C, synonymous), 13856 (A→G, L759 aspartic acid→glycine), and 15660 (T→C, synonymous). The Guinean EBOV strain showed 97% identity to EBOV strains from the Democratic Republic of Congo and Gabon. Phylogenetic analysis of the full-length sequences by means of Bayesian and maximum-likelihood methods revealed a separate, basal position of the Guinean EBOV within the EBOV clade (Figure 3).

Clinical and Epidemiologic Analysis

The prominent clinical features of the EBOV infection in the confirmed cases were fever, severe diarrhea, and vomiting; hemorrhage was less frequent. The case fatality rate in the initial cases was 86% (12 of 14 patients with a known outcome died). Confirmed cases originated from hospitals in Guéckédou, Macenta, Nzérékoré, and Kissidougou prefectures (Figure 1). We performed an epidemiologic look-back investigation of the transmission chains by reviewing hospital documentations and interviews with affected families, patients with suspected disease, and inhabitants of villages in which cases occurred.

According to the initial epidemiologic investigation, the suspected first case of the outbreak was a 2-year-old child who died in Meliandou in Guéckédou prefecture on December 6, 2013 (Figure 2). A second investigation confirmed the origin of the outbreak in Meliandou but revealed a somewhat different timing of the early events (including the death of Patient S1 at the end of December










JOURNAL ARCHIVE: - posted by H.V.O.M - Kerry Wayne Burgess 04:02 AM Pacific Time somewhere near Seattle Washington USA Saturday 28 December 2013 - http://hvom.blogspot.com/2013/12/see-its-this-kind-of-stuff-that-really.html


http://gateworld.net/atlantis/s5/transcripts/510.shtml

GateWorld


FIRST CONTACT

EPISODE NUMBER - 510

DVD DISC - Season 5, Disc 3

ORIGINAL U.S. AIR DATE - 09.26.08


DEX: So, you're going on this Daedalus thing?

KELLER: Yeah.

(She reaches for yet another bag but Ronon picks it up with his other hand.)

KELLER: Thank you.

(They walk out of the room.)

KELLER: I kind of have to. I'm the one that's gonna be administering the treatment -- if, you know, we ever get to that point.

DEX: Right. I think I should come with you on this.

KELLER: Really? Why?

DEX: I don't really trust these guys.



[JOURNAL ARCHIVE 28 December 2013 excerpt ends]


































http://who.int/csr/disease/ebola/ebola-6-months/guinea-chart-big.png?ua=1










JOURNAL ARCHIVE: - posted by H.V.O.M - Kerry Wayne Burgess 9:25 PM Pacific Time somewhere near Seattle Washington USA Friday 20 December 2013 - http://hvom.blogspot.com/2013/12/you-would-look-back-at-my-life-and.html


http://www.imdb.com/title/tt0114746/quotes

IMDb


Twelve Monkeys (1995)

Quotes


[first lines]

James Cole: Jose - psst! Jose, what's going on?

Jose: Bad news, man

James Cole: Volunteers?

Jose: Yeah. And they said your name.


[JOURNAL ARCHIVE 20 December 2013 excerpt ends]



- posted by H.V.O.M - Kerry Wayne Burgess 6:06 PM Pacific Time Spokane Valley Washington USA Friday 10 October 2014