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**Laidback Al** · October 19, 2014, 11:43 PM

Re: Up to half of Ebola infections may be asymptomatic and not infectious

Models today, for this current outbreak, do not account for asymptomatic infections, mostly because with over 10,000 confirmed, suspected, and probable cases in West Africa there is little time and personnel to assess this possibility. However, a 50% estimate of asymptomatic cases is unlikely despite the published Lancet article noted by Sharky’s post above. The article in the first link includes this:

Although a forceful response is needed, forecasts that ignore naturally acquired immunity from asymptomatic infections overestimate incidence late in epidemics. We illustrate this point by comparing the projections of two simple models based on the Ebola epidemic in Liberia, a model that does not account for asymptomatic infections, and another that assumes 50% of infections are asymptomatic and induce protective immunity.

So where does the estimate of a 50% asymptomatic infection rate come from? Here is the quote

Evidence suggests that many Ebola infections are asymptomatic,1, 2

So let us look at the sources cited from Bellan and colleagues’ article to justify a model with an assumption of 50% asymptomatic cases.

1 Heffernan RT, Pambo B, Hatchett RJ, Leman PA, Swanepoel R, Ryder RW. Low seroprevalence of IgG antibodies to Ebola virus in an epidemic zone: Ogooué-Ivindo region, Northeastern Gabon, 1997. J Infect Dis 2005; 191: 964-968. CrossRef | PubMed

2 Leroy E, Baize S, Volchkov V. Human asymptomatic Ebola infection and strong inflammatory response. Lancet 2000; 355: 2210-2215. Summary | Full Text | PDF(119KB) | CrossRef | PubMed

The 2005 Heffernan article states (link to full article)

We found that, after excluding 4 IgG-seropositive survivors of EBO hemorrhagic fever exposed during a documented outbreak, the seroprevalence of IgG antibodies to EBO-Z was 1.0% in a region where multiple epidemics of EBO hemorrhagic fever have occurred.

It is not clear how Bellan and colleagues translate this into a 50% asymptomatic infection rate.

The Leroy, Blaise, and Volchkov article from a study in Gabon states (link to full article)

Blood was collected from 24 close contacts of symptomatic patients. . . . 11 of 24 asymptomatic individuals developed both IgM and IgG responses to Ebola antigens, indicating viral infection.

These data do suggest that about 50% of the contacts of Gabon Ebola cases were infected but asymptomatic. But 24 individual is a small sample size. It is worth noting that the Gabon Ebola outbreak in 1996-1997 had less than 100 recorded cases (link). Contrast that with the more than 10,000 official cases in this current outbreak.

Providing a model with a 50% asymptomatic infection rate for this current Ebola outbreak is an interesting exercise. Bellan and colleagues’ expectations will be easily tested by mid January. They state:

Although the initial outbreaks are almost identical, by Jan 10, the model without asymptomatic infections projects 50% more cumulative symptomatic cases than the model that accounts for asymptomatic infection. This difference arises because asymptomatic infection contributes to herd immunity and thereby dampens epidemic spread.

It is premature to hope that herd immunity to the 2013-2014 Ebola outbreak will be achieved by an unrecognized abundance of asymptomatic cases by mid January.
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**gsgs** · October 20, 2014, 02:46 AM

Re: Up to half of Ebola infections may be asymptomatic and not infectious

when you get lots of dead viruses, would that give asymptomatic infection ?

dried body-fluids, mixing with dust, then after weeks blasted into the air
by vacuum cleaners and inhaled

or infection in some area of the body from where it can't spread to
other parts
well, ebola travels by blood

**Emily** · October 20, 2014, 02:49 AM

Re: Up to half of Ebola infections may be asymptomatic and not infectious

11 of 24 asymptomatic individuals developed both IgM and IgG responses to Ebola antigens, indicating viral infection

Couldn't this be simple antigenic stimulation rather than infection, (no viral RNA found with PCR)? They could be encountering deactivated ebola virus and getting something akin to a killed vaccine immune stimulation.

**kiwibird** · October 20, 2014, 03:32 AM

Re: Up to half of Ebola infections may be asymptomatic and not infectious

In this study there were findings that suggested the same for rabies exposure.

Seropositive Individuals Identified

In 2010, the researchers interviewed 92 residents of Truenococha and Santa Marta, 2 Peruvian communities in which rabies-carrying vampire bats are highly prevalent. They performed serological testing on 63 subjects. Of those surveyed, 54% reported being bitten by a bat. Risk factors for bat exposure included younger age, larger household size, and ownership of pets and/or livestock.2

Of the 63 sera samples tested, 9 had rabies-neutralizing antibody titers. All 9 of those subjects reported bat exposure, and one had been vaccinated. Positive titers were associated with older age but did not vary by gender.2

http://www.upmc-cbn.org/report_archive/2012/cbnreport_08102012.html

**gsgs** · October 20, 2014, 03:47 AM

Re: Up to half of Ebola infections may be asymptomatic and not infectious

Originally posted by Emily View Post

Couldn't this be simple antigenic stimulation rather than infection, (no viral RNA found with PCR)? They could be encountering deactivated ebola virus and getting something akin to a killed vaccine immune stimulation.

> IgM and IgG responses to Ebola antigens

doesn't that mean ebola-genetic code ?

**Emily** · October 20, 2014, 04:01 AM

Re: Up to half of Ebola infections may be asymptomatic and not infectious

Originally posted by gsgs View Post

> IgM and IgG responses to Ebola antigens

doesn't that mean ebola-genetic code ?

I hadn't seen your response when I posted. I think we are wondering about the same antigenic stimulation - I'm just wondering if the antibody response can be termed 'infection.'

**Tuffy** · October 20, 2014, 01:04 PM

Re: Up to half of Ebola infections may be asymptomatic and not infectious

If this is the case, I'd be interested for officials to test Mr. Duncan's 4 family members that shared an apartment with him while ill for 5 days, then with possible fomites for 7 more. What is the likelihood that they have antigens yet may remain symptomatic? I think it may unravel a bit more of the unknown. Not really sure they're willing or wanting to get tested anyway...especially since they're already stigmatized just for being around him 21 days ago.

**AlaskaDenise** · October 20, 2014, 02:24 PM

Re: Up to half of Ebola infections may be asymptomatic and not infectious

Originally posted by Tuffy View Post

If this is the case, I'd be interested for officials to test Mr. Duncan's 4 family members that shared an apartment with him while ill for 5 days, then with possible fomites for 7 more. What is the likelihood that they have antigens yet may remain symptomatic? I think it may unravel a bit more of the unknown. Not really sure they're willing or wanting to get tested anyway...especially since they're already stigmatized just for being around him 21 days ago.

If Duncan's famiy agreed to be tested, the tests would have the most validity if they were also tested 21 days ago, i.e, is any immunity long-standing or newly-acquired?

.

**Tuffy** · October 20, 2014, 02:48 PM

Re: Up to half of Ebola infections may be asymptomatic and not infectious

That would give the most validity for pure data for sure, but I think theoretically, we'd have to know their background a bit more to know if they could be exposed prior. If anything it could be SOME data to go on. Perhaps for future exposures if not now. Though personally I'm still curious.

**Emily** · October 20, 2014, 02:48 PM

Re: Up to half of Ebola infections may be asymptomatic and not infectious

Large serological survey showing cocirculation of Ebola and Marburg viruses in Gabonese bat populations, and a high seroprevalence of both viruses in Rousettus aegyptiacus

ZEBOV seropositivity in R. aegyptiacus bats likely reflects true viral infection, although passive antigenic stimulation cannot be ruled out. In Gabon, Megachiroptera members, including R. aegyptiacus, E. franqueti, M. torquata and H. monstrosus bats, consume the same fruits (especially Ficus spp). Bats of different species tend to visit the same trees, and interspecies virus transmission (or simple antigenic stimulation) could occur via infected saliva deposited on fruits. Hendra virus and Nipah virus transmission has been suggested to occur in this way between bats belonging to Asian Pteropus species [16].

The implication is that since ebola virus inactivates a few hours after drying, the bats could have just been mildly 'vaccinated' by viral particles.

High tech version:
Oral immunization of mice using transgenic tomato fruit expressing VP1 protein from enterovirus 71

No live virus or infection needed.

**zincfinger** · October 20, 2014, 02:52 PM

Re: Up to half of Ebola infections may be asymptomatic and not infectious

RE" Couldn't this be simple antigenic stimulation rather than infection, (no viral RNA found with PCR)? They could be encountering deactivated ebola virus and getting something akin to a killed vaccine immune stimulation."

EXACTLY!

There must be a continuum here: with exposure to very fresh body fluids, most of the virus being alive and infectious and, gradually over time, the virus degrading and an increasing proportion becoming non viable but still capable of provoking antibodies and that degrading until it's too degraded to provoke antigens.

I suspect that fresh material with mostly viable particles causes more severe disease while older material with a high proportion of non viable but still antigenic particles causes less severe disease because it provokes antibody production faster so the body can react quicker and more effectively to the disease. That would be a CONTINUUM between live and fully infectious virus all the way thru to what would amount to "inactivated" virus (except by natural processes and not by human intervention). Maybe the high level of antibodies to Ebola in endemic regions that clearly have not had enough outbreaks to cause that level of survivors*1 (or the population drop would have been noticed) is due to such a "naturally inactivated vaccine" process? This would (in part) explain why Ebola appears to die out readily in endemic areas, but once it gets outside them spreads more easily. The bats eat part of a fruit which drops on the ground and is consumed by animals. Bats eat at night and humans collect it during the day by which time it's mostly inactive due to natural degradation but still not too degraded to act as an antigen.

Experiences with early (pre vaccinia) smallpox vaccination would certainly appear to bear that out, IMHO: an early small vaccine was based on scabs from smallpox victims (rather than the different virus that Jenner introduced). It was sometimes ineffective and other times gave people the disease (which was why Jenner sought an alternative.) The problem was that whether it was useless, effective, or gave the recipient the disease depended on the stage of the disease at which the scab was removed and the handling and administration.

What gets REALLY interesting here is that IMHO the asymptomatic cases would possibly be spreading themselves*1 (at a lower rate than symptomatic ones) because they shed virus at lower levels (and perhaps in mostly already nonviable form as well, IMHO. they would tend to cause either very mild or asymptomatic cases. If so the "initiation of burn out" point would be where the level of immunity due to the total of both survivors of active cases AND of asymptomatic cases introduced enough herd immunity to get the ROI below one. Actual burn out would occur once that effect had caused the virus to die out of the population.

CRITICAL POINT: note that asymptomatic cases could be spreading themselves undetected if they mainly caused asymptomatic infections. There would IMHO be a "serial passage" effect of tending to make the virus more transmissible but at the same time, less virulent. (too virulent and the virus makes the person symptomatic and they get diagnosed and isolated so that variation is selected against. More transmissible and it spreads asymptomatically faster.

Another SPECULATION: maybe natural degradation causes some mutations before loss of viability to a degree. So could serial passage thru generations all infected with "stale" virus would possibly lead to a higher level of mutations? (sorry, I'm an incorrigible speculator)

Asymptomatic infections might just be a key part of the process by which pathogens gradually adapt to new hosts!

So to the past comment about maybe just infecting oneself and getting it over with (if you survive the gain is you no longer have to worry about it): maybe what you'd want to do is to expose yourself to people who'd had exposure [but was not symptomatic]

**alforddm** · October 20, 2014, 03:14 PM

Re: Up to half of Ebola infections may be asymptomatic and not infectious

CRITICAL POINT: note that asymptomatic cases could be spreading themselves undetected if they mainly caused asymptomatic infections. There would IMHO be a "serial passage" effect of tending to make the virus more transmissible but at the same time, less virulent. (too virulent and the virus makes the person symptomatic and they get diagnosed and isolated so that variation is selected against. More transmissible and it spreads asymptomatically faster.

The problem with this is that you would have a broken chain of transmission which by all accounts has not been happening. To have a chain of totally asymptomatic infections that never caused severe infection, it would probably have to mutate so much from the current strain as to no longer be the current strain.

**AlaskaDenise** · October 20, 2014, 03:19 PM

Re: Up to half of Ebola infections may be asymptomatic and not infectious

...So to the past comment about maybe just infecting oneself and getting it over with...

aka old-fashioned vaccination - back when there weren't vaccinations for everything, many mothers purposely exposed their kids to another child with an active infection for various strategic reasons.

.

**Vibrant62** · October 20, 2014, 03:23 PM

Re: Up to half of Ebola infections may be asymptomatic and not infectious

I think there is a potential flaw in this argument. An alternate hypothesis.

A key part of ebola's infective mechanism is the disablement of the normal innate immune response, so that the virus replicates unhindered by an immune response, until viral load is so high that the innate immune system kicks in.

Isnt it more likely that asymptomatic cases are those where Ebola's disabling mechanism does not work properly, and the hosts immune system kicks in early (as it would for other infections) and clears the virus without particular incident, i.e it never progresses to a high viral load, immune system deregulation, and serious disease.

This would suggest genetic variations on the part of susceptible hosts, rather than intrinsic differences in the virus per se?

And if it were true, a therapeutic target would be something that blocks this viral masking mechanism?

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Lancet: Up to half of Ebola infections may be asymptomatic and not infectious

Lancet: Up to half of Ebola infections may be asymptomatic and not infectious

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