Deader guide to Ebola.
Andre Willers
13 Aug 2014
“Dead , Deader , Deadest !
What I tell you three times is true.” … The Snarkier Bellman .
Synopsis :
Ebola and its cousins can vector through plants as well as
animals . A versatile and tough beastie .
Discussion :
1.Are plants the missing Ebola reservoirs and vector ?
If so , humans are in deep , deep doo-doo .
1.1 Antibodies to Ebola have been found in plants . See
Appendix A , B and C below .
This means that the plants must have been infected with the
virus .
This means that the virus could hide in the plants .
1.2.The virus seems to be an aggressive coloniser .
Appendix D indicates bird vectoring of a close relative of
Ebola (Nile Virus)
2. If human staplefood plants become infected , famine would
result .
3.Tobacco (see Appendix A , B) would be a prime candidate .
4.The virus seems old and sophisticated . Probably capable
of multiple behaviours only now being switched on .
5.A Quick and dirty way to estimate plateau populations for an epidemic :
See Appendix E
Ebola and Smallpox seem about the same threat level (roughly
~50% level of population at plateau) , ie 7.5 Bn dead .
But HIV is about double as dangerous (~25% survival ) .
Both combined as at present , gives 0.5*0.25 ~.125 , ie
12.5% survival .
Better make friends with those nifty vaccines fast .
Good luck !
Andre
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Appendix A
Plant-made antibodies used as therapy for Ebola in humans:
post-exposure prophylaxis goes green!
Yes, I
know you fans of ViroBlogy like Ebola – and just coincidentally, I was
desperately trying to finish a review on “Plant-based vaccines against viruses”
against a backdrop of an out-of-control Ebola epidemicin West Africa, when three
different people emailed me different links to news of use of a plant-made
monoclonal antibody cocktail. I immediately included it in my review –
and I am publishing an excerpt here, for informations’ sake. Enjoy!
Plantibodies
against Ebola
The
production of anti-Ebola virus antibodies has recently been explored in plants:
this could yet become an important part of the arsenal to prevent disease in
healthcare workers, given that at the time of writing an uncontrolled Ebola
haemorrhagic fever outbreak was still raging in
West Africa, and the use of experimental solutions was being
suggested (Senthilingam,
2014). For example, use of a high-yielding geminivirus-based
transient expression system in N benthamianathat is particularly
suited to simultaneous expression of several proteins allowed expression of a
MAb (6DB) known to protect animals from Ebola virus infection, at levels of 0.5
g/kg biomass (Chen et al., 2011). The same group also used the same vector
system (described in detail here (Rybicki and Martin, 2014)) in lettuce to
produce potentially therapeutic MAbs against both Ebola and West Nile viruses
(Lai et al., 2012).
A more
comprehensive investigation was reported recently, of both plant production of
Mabs and post-exposure prophylaxis of Ebola virus infection in rhesus macaques
(Olinger et al., 2012). Three Ebola-specific mouse-human chimaeric MAbs
(h-13F6, c13C6, and c6D8; the latter two both neutralising) were produced in
whole N benthamiana plants via agroinfilration of magnICON
TMV-derived viral vectors. A mixture of the three MAbs – called MB-003 – given
as a single dose of 16.7 mg/kg per Mab 1 hour post-infection followed by doses
on days 4 and 8, protected 3 of 3 macaques from lethal challenge with 1 000 pfu
of Ebola virus. The researchers subsequently showed significant protection with
MB-003 treatment given 24 or 48 hours post-infection, with four of six monkeys
testing surviving, compared to none in two controls. All surviving animals
treated with MB-003 experienced insignificant if any viraemia, and negligible
clinical symptoms compared to the control animals. A significant finding was
that the plant-produced MAbs were three times as potent as the CHO
cell-produced equivalents – a clear case of plant production leading to
“biobetters”. A follow-up of this work investigated efficacy of treatment with
MB-003 after confirmation of infection in rhesus macaques, “according to a
diagnostic protocol for U.S. Food and Drug Administration Emergency Use
Authorization” (Pettitt et al., 2013). In this experiment 43% of treated
animals survived, whereas all controls tested here and previously with the same
challenge protocol died from the infection.
In news
from just prior to submission of this article, a report quoted as coming from
the National Institute of Allergy and Infectious Diseases states that two US
healthcare workers who contracted Ebola in Liberia were treated with a cocktail
of anti-Ebola Mabs called ZMapp – described as a successor to MB-003 –
developed by Mapp Pharmaceutical of San Diego, and manufactured by Kentucky
BioProcessing (Langreth et al.,
2014). Despite being given up to nine days post-infection in one
case, it appears to have been effective (Wilson and
Dellorto, 2014).
A novel
application of the same technology was also used to produce an Ebola immune complex
(EIC) in N benthamiana, consisting of the Ebola
envelope glycoprotein GP1 fused to the C-terminus of the heavy chain of the
humanised 6D8 MAb, which binds a linear epitope on GP1. Geminivirus
vector-mediated co-expression of the GP1-HC fusion and the 6D8 light chain
produced assembled immunoglobulin, which was purified by protein G affinity
chromatography. The resultant molecules bound the complement factor C1q,
indicating immune complex formation. Subcutaneous immunisation of mice with
purified EIC elicited high level anti-GP1 antibody production, comparable to
use of GP1 VLPs (Phoolcharoen et al., 2011). This is the first published
account of an Ebola virus candidate vaccine to be produced in plants.
References
Chen,
Q., He, J., Phoolcharoen, W., Mason, H.S., 2011. Geminiviral vectors based on
bean yellow dwarf virus for production of vaccine antigens and monoclonal
antibodies in plants. Human vaccines 7, 331-338.
Lai,
H., He, J., Engle, M., Diamond, M.S., Chen, Q., 2012. Robust production of
virus-like particles and monoclonal antibodies with geminiviral replicon
vectors in lettuce. Plant biotechnology journal 10, 95-104.
Langreth,
R., Chen, C., Nash, J., Lauerman, J., 2014. Ebola Drug Made From Tobacco Plant
Saves U.S. Aid Workers. Bloomberg.com.
Olinger,
G.G., Jr., Pettitt, J., Kim, D., Working, C., Bohorov, O., Bratcher, B., Hiatt,
E., Hume, S.D., Johnson, A.K., Morton, J., Pauly, M., Whaley, K.J., Lear, C.M.,
Biggins, J.E., Scully, C., Hensley, L., Zeitlin, L., 2012. Delayed treatment of
Ebola virus infection with plant-derived monoclonal antibodies provides
protection in rhesus macaques. Proceedings of the National Academy of Sciences
of the United States of America 109, 18030-18035.
Pettitt,
J., Zeitlin, L., Kim do, H., Working, C., Johnson, J.C., Bohorov, O., Bratcher,
B., Hiatt, E., Hume, S.D., Johnson, A.K., Morton, J., Pauly, M.H., Whaley,
K.J., Ingram, M.F., Zovanyi, A., Heinrich, M., Piper, A., Zelko, J., Olinger,
G.G., 2013. Therapeutic intervention of Ebola virus infection in rhesus macaques
with the MB-003 monoclonal antibody cocktail. Science translational medicine 5,
199ra113.
Phoolcharoen,
W., Bhoo, S.H., Lai, H., Ma, J., Arntzen, C.J., Chen, Q., Mason, H.S., 2011.
Expression of an immunogenic Ebola immune complex in Nicotiana benthamiana.
Plant biotechnology journal 9, 807-816.
Rybicki,
E.P., Martin, D.P., 2014. Virus-Derived ssDNA Vectors for the Expression of
Foreign Proteins in Plants. Current topics in microbiology and immunology 375,
19-45.
Senthilingam,
M., 2014. Ebola outbreak: Is it time to test experimental vaccines? CNN.
Wilson,
J., Dellorto, D., 2014. 9 questions about this new Ebola drug. CNN.
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Appendix B
A similar plant as the
one harbouring Ebola antibodies in Appendix A is found widely in West Africa.
It could be a missing
reservoir and vector .
“Caesalpinia benthamiana (Baill.) Herend. & Zarucchi
|
Protologue
Ann. Missouri Bot. Gard. 77(4): 854 (1990). Family Caesalpiniaceae (Leguminosae - Caesalpinioideae). Synonyms Mezoneuron benthamianum Baill. (1866). Origin and geographic distribution Caesalpinia benthamiana is widespread in West and Central Africa, where it occurs from Senegal to Gabon. Uses In Senegal an infusion of the dried roots is drunk or used as a bath against general malaise. In Senegal, Guinea and Nigeria a decoction of roots, bark and leaves is used to cure urethral discharge. In Guinea the young leaves are chewed as a depurative and masticatory. In Côte d’Ivoire Caesalpinia benthamiana stem liquid is dropped in the eye to cure inflammation and cataract. In Côte d’Ivoire and Nigeria stems and roots are used for dental hygiene, to sooth toothache and as an aphrodisiac. Leaves are applied as a paste to treat snakebites. In Senegal, Sierra Leone and Ghana wounds, skin infections, piles and ulcers are treated with a watery macerate of leafy twigs, mashed-up leaves or leaf ash. The leaves are mildly laxative and used to cure colic. Patients suffering from hookworm or Guinea worm eat the young leaves as a treatment. Patients suffering from impotence related to venereal diseases are prescribed a macerate of leafy twigs. A root decoction is drunk to cure dysentery. The roots are added to palm wine to increase the strength or its aphrodisiac properties. In Gambia Caesalpinia benthamiana is grown in garden fences to make them impenetrable. When cut the stems yield drinking water.” |
See also
Googled
list of plants with antibodies .
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Appendix C
Abstract
“ Notably, although rhabdoviruses span all continents and
exhibit a wide host range, infecting plants, invertebrates, vertebrate animals,
and humans, relatively few are known to cause human infections. Rabies virus
(RABV) and related viruses from the Lyssavirus genus and Chandipura virus (CHPV) from
the Vesiculovirus genus are known to cause acute
encephalitis syndromes[11], [12]. Other viruses from the
genus Vesiculovirus cause vesicular stomatitis (mucosal
ulcers in the mouth) and “flu-like” syndromes in both cattle and humans [13].”
Xxxxxxxxxxxxxxxxxxxxxxxxxxxx
Appendix D
·
SEROLOGIC EVIDENCE FOR WEST NILE VIRUS
TRANSMISSION IN PUERTO RICO AND CUBA
Arbovirus Laboratories, Wadsworth Center, New York State
Department of Health, Slingerlands, New York; Smithsonian Environmental
Research Center, Edgewater, Maryland
Abstract
During the spring of 2004, approximately 1,950 blood specimens
were collected from resident and Nearctic-Neotropical migratory birds on the
Caribbean islands of Puerto Rico and Cuba prior to northerly spring migrations.
Eleven birds and seven birds, collected in Puerto Rico and Cuba, respectively,
showed evidence of antibody in a flavivirus enzyme-linked immunosorbent assay.
Confirmatory plaque-reduction neutralization test results indicated
neutralizing antibodies to West Nile virus in non-migratory resident birds from
Puerto Rico and Cuba, which indicated local transmission.
Xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx
Appendix E
Quick and dirty threat estimate for contagious disease .
|
Deader Ebola Guide .
|
||||||||||||
|
13-Aug-14
|
||||||||||||
|
Quick and dirty plateau estimate.
|
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|
Definitions in
|
||||||||||||
|
http://en.wikipedia.org/wiki/Plateau_principle
|
||||||||||||
|
For arbitrary unit time t , Rnought cases flow in = Ks = Rnought
|
. The infected ones .
|
|||||||||||
|
The elimination rate Ke = v*Rnought , where v is virulence as
rate . The ratio of infected ones that die . V=0.6 for Ebola .
|
||||||||||||
|
Css=Rnought/(Rnought*v)
|
||||||||||||
|
Css= 1/v
|
||||||||||||
|
Cnought=Rnought by definition , and t=1 (ie only one tick at
staedy state .
|
||||||||||||
|
Ct=Cnought+(Css-Cnought)(1-e^(-Ke *t)) …. Where Ct is to be found for t=1
|
||||||||||||
|
from wiki/Plateau . The general relation at steady state .
|
||||||||||||
|
Lp=
|
Ct/Cnought= 1+(1/(v*Rnought)
- 1 )(1 - e^(-v*Rnought) )
|
|||||||||||
|
Lp is ratio of living to initial population after a steadystate
plateau has been reached .
|
||||||||||||
|
Rnought
|
||||||||||||
|
http://en.wikipedia.org/wiki/Basic_reproduction_number
|
||||||||||||
|
Population level of living at plateau stage.
|
|
|
|
|
|
|||||||
|
|
|
|||||||||||
|
Lp
|
Rnought
|
|
||||||||||
|
v
|
1
|
2
|
3
|
4
|
5
|
6
|
7
|
17
|
18
|
|||
|
0.1
|
186%
|
173%
|
160%
|
149%
|
139%
|
130%
|
122%
|
66%
|
63%
|
|||
|
0.2
|
173%
|
149%
|
130%
|
114%
|
100%
|
88%
|
78%
|
32%
|
30%
|
|||
|
0.3
|
160%
|
130%
|
107%
|
88%
|
74%
|
63%
|
54%
|
20%
|
19%
|
|||
|
0.4
|
149%
|
114%
|
88%
|
70%
|
57%
|
47%
|
40%
|
15%
|
14%
|
|||
|
0.5
|
139%
|
100%
|
74%
|
57%
|
45%
|
37%
|
31%
|
12%
|
11%
|
|||
|
0.6
|
130%
|
88%
|
63%
|
47%
|
37%
|
30%
|
25%
|
10%
|
9%
|
|||
|
0.7
|
122%
|
78%
|
54%
|
40%
|
31%
|
25%
|
21%
|
8%
|
8%
|
|||
|
0.8
|
114%
|
70%
|
47%
|
34%
|
26%
|
21%
|
18%
|
7%
|
7%
|
|||
|
0.9
|
107%
|
63%
|
41%
|
30%
|
23%
|
19%
|
16%
|
7%
|
6%
|
|||
|
1
|
100%
|
57%
|
37%
|
26%
|
21%
|
17%
|
14%
|
6%
|
6%
|
|||
|
|
|
|
|
|
|
|
|
|
|
|||
|
Population level of of dead at plateau stage
|
|
|
|
|
|
|||||||
|
|
|
|||||||||||
|
Dp
|
Rnought
|
|
||||||||||
|
v
|
1
|
2
|
3
|
4
|
5
|
6
|
7
|
17
|
18
|
|||
|
0.1
|
-86%
|
-73%
|
-60%
|
-49%
|
-39%
|
-30%
|
-22%
|
34%
|
37%
|
|||
|
0.2
|
-73%
|
-49%
|
-30%
|
-14%
|
0%
|
12%
|
22%
|
68%
|
70%
|
|||
|
0.3
|
-60%
|
-30%
|
-7%
|
12%
|
26%
|
37%
|
46%
|
80%
|
81%
|
|||
|
0.4
|
-49%
|
-14%
|
12%
|
30%
|
43%
|
53%
|
60%
|
85%
|
86%
|
|||
|
0.5
|
-39%
|
0%
|
26%
|
43%
|
55%
|
63%
|
69%
|
88%
|
89%
|
|||
|
0.6
|
-30%
|
12%
|
37%
|
53%
|
63%
|
70%
|
75%
|
90%
|
91%
|
|||
|
0.7
|
-22%
|
22%
|
46%
|
60%
|
69%
|
75%
|
79%
|
92%
|
92%
|
|||
|
0.8
|
-14%
|
30%
|
53%
|
66%
|
74%
|
79%
|
82%
|
93%
|
93%
|
|||
|
0.9
|
-7%
|
37%
|
59%
|
70%
|
77%
|
81%
|
84%
|
93%
|
94%
|
|||
|
1
|
0%
|
43%
|
63%
|
74%
|
79%
|
83%
|
86%
|
94%
|
94%
|
|||
|
|
|
|
|
|
|
|
|
|
|
|||
|
http://en.wikipedia.org/wiki/List_of_human_disease_case_fatality_rates
|
||||||||||||
|
Disease
|
Transmission
|
R
0
|
R
0
|
v
|
Lp
|
THREAT
|
||||||
|
Airborne
|
12–18
|
18
|
0.03
|
136%
|
|
|||||||
|
Airborne droplet
|
12–17
|
17
|
0.01
|
176%
|
|
|||||||
|
Saliva
|
6–7
|
7
|
0.1
|
122%
|
|
|||||||
|
Airborne droplet
|
5–7
|
7
|
0.3
|
54%
|
X
|
|||||||
|
Fecal-oral route
|
5–7
|
7
|
0.05
|
155%
|
|
|||||||
|
Airborne droplet
|
5–7
|
7
|
0.0005
|
199%
|
|
|||||||
|
Airborne droplet
|
4–7
|
7
|
0.01
|
190%
|
|
|||||||
|
HIV/AIDS
|
Sexual contact
|
2–5
|
5
|
0.9
|
23%
|
X
|
||||||
|
Airborne droplet
|
5
|
0.11
|
135%
|
|
||||||||
|
Airborne droplet
|
3
|
0.025
|
189%
|
|
||||||||
|
|
|
|||||||||||
|
Bodily Fluids
|
1–4
|
4
|
0.6
|
47%
|
X
|
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