From their website, it appears to be a PCRbased test with a lot of the reagents pre-loaded on what they are calling a FilmArray. The reaction is then run in accordance with software based instructions. I’ve not used such a system, but PCR the old-fashioned way was a PITA, as much art form as science. At least that’s how I recall it from the early days.
The good news as it affect Ebola testing is that PCR based tests directly test for the genetic material of the virus. They are very sensitive and can, in theory, test early in the infection for many viral infections. At least with some diseases they have been able to use such techniques to test before onset of symptoms. Hopefully that will also be the case for the Ebola testing.
A PCR test the really old-fashioned (mid 1980’s) way would have taken several hours at a minimum and possibly more than a day, depending upon how many cycles were needed. BioFire claims to output results in about an hour. Nice.
I would be interested in seeing the literature cite for this, other than reassurances by experts–part of whose job is preventing the undereducated from panicking. We do not do studies getting people with known infections but no symptoms to slobber on others or exchange sexual fluids to see when, exactly, they are shedding free virus capable of transmitting Ebola disease.
I am not saying studies do not exist; only that I have not seen them.
I would reply to the OP by saying that, in experimental studies with deliberately infected animals, an IgM response can be seen on ELISA as early as 6 days after infection. I’m not aware that PCR can detect infection any sooner, so something on the order of a week or so after infection is probably the earliest we could decide with reasonable probability that you have been infected with Ebola.
Now, when you can give it to someone else is also an interesting question, and we’ll probably never be able to give an exact answer to that. Certainly by the time you become symptomatic, you are at risk for transmitting the virus. But symptoms are on a spectrum, and are by definition subjective as well as objective. Moreover, they are quite person-dependent. My fatigue meter may be different from yours. Even my basal temperature might be different from yours.
Sometime between the time the virus first takes hold in a host, and the time that patient is feverish, sweating, bleeding, passing loose stools and puking their guts out, they become infectious to others. It’s not like one moment they aren’t able to transmit the virus, and the next they are. It’s just that, before they start sweating/vomiting/diarrhea/bleeding etc, they don’t transmit the virus just by walking around and breathing (because the virus wants a bit of moisture as a mechanism of transfer).
I assure you that, if the CDC knew someone had Ebola, they would not let him wander around until such time as he became symptomatic.
The idea of waiting for symptoms is a practical screen, and not some kind of confidence on the part of medical professionals that an asymptomatic patient cannot transmit Ebola. It’s more like, “They aren’t likely to transmit it, because how would that transmission occur?” The virus is inside the host, taking over cells and replicating itself, and at some point free virus that can infect others is running around in fluids. While that may be nearer the point of symptoms than the time of infection, it’s definitely not true that symptoms precede the possibility of infecting others.
With Dr Spencer’s fiance Morgan Dixon, for example, transmission might occur much earlier with kissing or sexual activity. Not on a first day, perhaps, but certainly before a clinically-apparent fever. (I’m not suggesting any of that contact occurred; only using that as an example).
And you would be silly to wait for clinical symptomatology to occur before asking a patient with a known infection to be quarantined.
We can’t screen every exposed individual. We can’t get sucked into the panic of the undereducated and assume everything and everyone in the vicinity of the exposed is somehow now contaminated. But we also should not get confused about the difference between CDC recommendations that people are not contagious until they are symptomatic and a medical understanding that transmission is nevertheless still possible with the right type of contact prior to overt symptoms.
Below is a good article on the mechanics and timeline of an Ebola infection. It’s not like you get infected and then POW you are the Ebola king. Studies on primates show that in asymptomatic stages, Ebola is concentrated in lymph nodes and the spleen. Over time, it replicates to the point where the virus is detectable in blood, followed several days later by other fluids. This coincides with the onset of symptoms (which seem to be from attacks on the liver). As the disease progresses, the virus replicates and the viral load in fluids gets higher and higher, making it more and more infectious. This is why dead bodies are such a danger- they happen right when the viral load is highest.
It’s known that some people get infected with Ebola but never show symptoms. Scientists have been on the lookout for outbreaks tied to those people, but have not found them. Given the poor public health systems in the affected area, it’s completely possible that something has been missed. But so far, it appears that aymptomatic people are not contagious.
What are the guidelines for people who are not returning medical workers, such as people on a work visa. Same question for illegal aliens?
It’s easy to monitor professionals in the medical field. They’re self monitoring. It’s less so with people who avoid monitoring, deny their medical conditions, abuse drugs, or have random sex with strangers.
Right now the disease is limited to nations with low travel rates. It’s a blessing in disguise that it could be stopped in it’s tracks by limiting that travel. It costs us nothing to ban travel from such locations until we get the disease under control.
As it stands now, the best we can hope for is to stop infected people who are showing signs upon entry into the country. Our current strategy does not stop infected people who do not show signs upon entry.
It’s easy to monitor professionals in the field, as long as you don’t subject them to needless travel bans. The moment you institute travel bans, you are going to have a lot of plucky idealistic doctors “losing” their bassports in Brussels.
The number of people from the affected countries with US visas is tiny. And Liberians are not being smuggled in to the US. Any undocumented Liberians are visa overstays, and are not likely to be a danger.
Yes that goes without saying. But it makes sense to quarantee doctors prior to traveling back to their country of origin. It should be part of the process.
That’s interesting. You know how many undocumented aliens we have in this country.
I did not find that article especially helpful in addressing this question:
At what point post-infection is virus actively shed in bodily fluids?
PCR and ELISA detection studies–to the best of my knowledge–have largely been carried out in symptomatic populations, felt already to have a high risk for Ebola. There may be animal model studies (I gave you one showing IgM detectability, but not virual shedding at 6 days) that correlate symptoms (as best as we can infer them from animals) and viral shedding.
I am wondering what the source of your confidence is that “asymptomatic” patients are not contagious beyond the general idea that they are not sweating, vomiting, etc.
Is it the case that you think it’s perfectly safe to share bodily fluids with a person infected with Ebola who is not yet exhibiting symptoms? If so, I can assure you that you have confused “contagious” in the broad public health sense (they are not spewing virus in bodily fluids all over the place) with “contagious” in the sense that, at some point prior to active symptoms, it’s entirely possible an individual exposed to their fluids could get Ebola.
Neither viral transit into body fluids nor symptoms is some sort of exact point in time, and the idea that if I have Ebola but don’t have a fever so I can’t transmit it to you, is quite naive in my view.
I agree it is completely true that an individual with a very early Ebola infection is unlikely to transmit the disease. But I doubt studies have been done with (for example) daily RT-PCRs or ELISAs on exposed patients to see when there was evidence of free virus in fluids marking high risk for transmission from those fluids, and correlating that with symptoms. Most of the early detection studies I have seen in humans have been done on patients already symptomatic.
I am reasonably sure that the CDC would recommend near-complete immediate isolation for an individual who received an Ebola-tainted transfusion, for example. They wouldn’t say, “Hey; just come back when you get symptoms and we’ll put you in isolation then.”
Why? So they can infect more people if they are positive? Or so they can take up desperately needed resources? Or is it to convince health worked- 15,000 of which are needed (a few hundred are out there now)-- not to go?
Keeping people in-country leads to more Ebola, and that eventually means more US Ebola.
When it comes to African immigration, I kind of do.
Read the article here to get an idea of the concern that non-public-facing workers are willing to express. After the reassuring article come some of the more sober replies in the comment section:
*" 9 days ago
I am a hospital epidemiology and infectious disease consultant guiding hospital and public health in my region, currently for Ebola. In searching for scholarly support of the cited incubation period and viral infectivity during that period, I have not been able to find any primary source document that actually looks at measuring viremia and infectivity during the the period of incubation, even in an individual, let alone a cohort of potentially exposed humans. Based on what I have found, it appears we actually do not know when viremia or viral shedding in different body fluids begins, and if this overlaps with the clinically silent (asymptomatic) incubation period.
Noted is the excellent review posted by IDSA and Oxford online by J. ter Meulen on Filoviruses which mentions cases of asymptomatic Ebola infection in passing. This implies there are patients who have asymptomatic viremia, survive and become immune, which implies viremia occurs in the incubation period. Notable, also, is ter Meulen’s recommendation for negative pressure isolation and protective garb in handling the virus.
There are a number of sources that cite measurements of viral RNA or plaque counts on day zero of active disease, the time when CDC and others state that infectivity and transmission can begin. All of these cite viremia in the range of 50,000 to 10 million RNA copies per cc on the first day of symptoms. If viremia is this high at the onset of clinical disease, then surely, there must be significant viremia and likely viral shedding from other fluids before the end of the asymptomatic incubation period. See J. Virol.April 2004 vol.78 no. 8 4330-4341 for one example.
CDCs statement that humans are not contagious during the incubation period is an equivocation of terms, hopefully not on purpose. It is highly likely based on current scientific evidence that viremia is present in the late stages of asymptomatic incubation and body fluids are probably infectious proportional to their viral content during incubation, a phenomenon that has not been studied and published. E.g., blood transfusion from such an asymptomatic donor incubating Ebola would likely be lethal to the recipient (and note the joint statement by the Red Cross and others just two days ago). Fortunately, asymptomatic but incubating Ebola infected patients usually still maintain continence of their body fluids and blood, and thus, by virtue of this, not contagious. This accounts for CDCs statement to the public I believe. But to say that the incubating patients body fluids is free from infectious virus is not substantiated by the evidence, either positively or negatively as best I can find.
Please correct me if I am wrong, but I cannot find any evidence of viral measurement during the incubation period of individuals infected but still asymptomatic. All the published human studies focus on symptomatic patients and what happens after clinical disease is evident."*
“Viral analysis with PCR amplification” … needs …, “biopsies.” Means what? A blood sample plus a piece of tissue extracted under anesthesia?
Just a blood sample? And a the “possibly a day time” to wait for results? How difficult is it to run the labs, who is equipped to do so, and how expensive?
[apologies for no in-thread upcites.]
I have not gone to the cites. Can someone explain clearly here?
I think it’s interesting that the answer to OP is unknown, I believe, to most everybody in the public, using John Q. Leo Bloom as an example, as are my obvious questions about what the tests comprise. And the “fever?–flu?–quarantine” discussion is is so intense already (as this thread is evidence).
Ok, I, for one, have, at least as so broadly stated. The CDC is not the UN, nor is its Government, and I hope factors the chance and consequences of deaths and epidemic, minuscule or otherwise, differently for Americans than non-Americans.
And yes, everyone’s blood is as red as everyone else’s, and I’m aware that any overseas humanitarian mission the U.S. has undertaken has had “minuscule”–actually at times significant–risk to American lives.
I think that’s a crap cite because 90% of it is rhetorical bullshit about how he’s better, smarter and more useful and his detractors. Maybe true, but meaningless to the point under discussion.
??? how is quarantining someone prior to entry going to infect more people? Load your kindle up with some books and veg out for 3 weeks. The President can hand out medals and a thank you tax deduction upon entry.
OK, easy enough, how many illegal immigrants are there and where are they?
You’re talking about people who have already donated weeks of their lives in horrible conditions doing a horrible job. Now - without a real health concern - you want them to give up another three weeks. Another three weeks with no income, without planning their weddings, visiting their dying grandmothers, hugging their kids… and, again, so far as we best know right now, completely without need. There’s some concern that either they won’t go, and ebola will continue its spread in Western Africa and find its way here through Europe or Asia or Australia, or they will go, and they’ll come home through Europe or Asia or Australia, “losing” the documentation that they were in Western Africa on the way.
I’m not even sure I’m in favor of temperature screening at airports, to be honest. I’m sure sales of Tylenol and Ibuprofen are booming as people figure out that if they get a fever on the plane, no matter where they are flying from, they’re going to be imprisoned on arrival. Take a Tylenol, and at least you can go home first and unpack before you call your doctor and make arrangements for the next three weeks. And that makes everyone’s job harder, and actually may put people at risk.
Self-monitoring, sure, absolutely. But asymptomatic quarantine is a bridge too far in my book, with what we currently know. If it turns out that it doesn’t work and people are suddenly popping up with ebola, then we should revisit that decision. But so far, they’re not. Self-monitoring is working, even despite the mistakes that people have made. The patient who died didn’t give it to a single family member, even though he was actively, indisputably, symptomatic around them and they were caring for him.
It’s almost certain more people will die this year of influenza. Are you in favor of quarantining all of the people who are exposed to people who get the flu?
Well, I got a flu shot this year, so there’s that. OTOH, I think you left out that most of them are paying their own travel expenses, OTOOH, stopping the virus gaining a foothold in North and South America should entail different protocols than containing it where it’s already loose in the wild. There is no rabies in Hawaii, for example, and they work really hard at keeping it that way.
The answer to the OP is that we can, in theory, figure out that you have Ebola within about a week of your infection by looking for the body’s immune response to Ebola.
The answer to the question of when your bodily fluids become infectious is unknown, but it’s closer to the time of symptomatology than infection. However since symptoms exist along a gray line without a sharp demarcation, that’s not super helpful.
What is helpful is that even if your fluids are infectious, if you aren’t slobbering them around or boinking your girlfriend, you are not going to spread Ebola.
I don’t have a good answer to the quarantine question, because it essentially depends upon personal responsibility and compliance for those not quarantined. And health workers come into intimate contact with a lot more people–including immunocompromised people–than a cubicle worker. The fundamental dilemma is that it is quite likely (my personal, educated, opinion) that you shed virus in body fluids for at least a day or two prior to the body mounting enough of a response to a viremia to present clinically. Proving that would require a large prospective study culturing body fluids of exposed patients on a very frequent basis (once or twice a day) and seeing who is shedding live virus relative to symptoms onset in the group who ended up contracting Ebola. You would have to track their symptomatology and correlate the time of onset with the time the viral cultures turned positive. This is not a very realistic study proposal in the US and is probably impossible in the milieu of african countries where the virus is epidemic. Even then you would end up with a soft answer. What if you get symptomatic 12 hours after developing a viremia? How do you instruct, “Be particularly cautious for 12 hours before you get symptoms”?
As a physician who does medical missionary trips (typically 2-3 week stints) to underdeveloped countries, I am sensitive to the notion that asking me for 6 weeks of time instead of 3 would probably keep me from serving. I personally think the best solution is to home quarantine, and set up funds to pay volunteers who serve in Ebola environments for their quarantine time. As a total amount of money it would be fairly trivial.
Who is paying your bills? Who is watching your kids? Who is bringing you the nachos you have been craving for weeks?
More importantly, if you do get sick, how sure do you feel that you are getting home? Because if I’m not 100% sure I am going to an American hospital, and I going to see my daughter and husband and mother before I die, I am not going. No way. If i think for a minute some scaremongering opportunist is goibg to block my flight, I’m done. Discussion over.
These are real people, flaws and all. Very few of them are super-excited to go watch a bunch of people die miserably to begin with. We don’t have infinite money to make up for how shitty the work is. Make it even worse, and it will get even harder.
There are a few hundred people out there now. We need more than 10,000. We can’t pay them all a million bucks a month. Where are they going to come from?
If history is any indication, they just might send that person home. There was one case of a lab worker at USAMRIID at Ft Detrick, MD who suffered a needle stick injury while working with Ebola. She was sent home overnight, albeit to return after packing her things.
To borrow from Wikipedia, a biopsy is "the medical removal of tissue from a living subject to determine the presence or extent of a disease. " It may be as simple as a largish needle inserted under local anesthesia (if any). It may be more involved and require anesthesia. Biopsies are frequently used to help diagnose cancers.
PCR testing for diagnostic purposes requires a sample of whatever tissue you think might show viral particles. A biopsy is one way to get a sample. But it is much more intrusive than a blood draw.
Based upon what we do know about the course of an Ebola infection (some of which is from animal models), in early stages of the disease the virus starts attacking certain internal tissues. The mononuclear phagocyte cells (a type of immune system cell) of the spleen and liver are indeed early targets. There can be accumulations of such cells in the lymph nodes as well. The virus goes on to attack fibroblasts and parenchymal cells of other internal organs.
In layman’s terms that means that the virus attack starts with infection certain types of immune cells that are present in the liver, spleen, and lymph nodes. It moves on to attack other organs. Infected immune system cells and/or virus particles may move around in the blood as the infection spreads from one tissue to another.
In order to do a test for the virus using PCR techniques we need a sample. If you took biopsy of the spleen, liver, and/or lymph nodes very early in the infection (even before symptoms start) you may detect virus. This might even detect the virus before it would show in a blood sample.
But wait a few days later and the virus will have replicated in the initial organs and spilled out to spread around the body in the bloodstream and wreak its havoc. Then a simple blood sample would be enough to test and confirm the presence of virus.
Testing using PCR
I am familiar with the bad old days of PCR tests in the mid 1980s. PCR had a reputation of being a bit finicky, with lots of chances to screw things up. Sometimes you worked for hours on a sample only to get no results because something was a little too hot, a little too cold, or wasn’t at just the right temperature for the right about of time. Apparently it has gotten a lot better since then.
Each time you run the sample through a complete PCR cycle you double (more or less) the amount of genetic material of interest. Run it through 30 cycles and you have increased the amount by more than a billion fold. But each cycle can take around 25-30 minutes, so 30 cycles can take 15 hours (or more). Screw things up and it might take more than a day.
In short, PCR is a chemical way to duplicate genetic material. Think of it as running your test sample through a special chemical photocopier that allows you to multiply the amount of very specific genetic material. The more dilute the initial sample, the more cycles of PCR you need to run.
The equipment is not complex. Now you can find instructions on the internet how to build an open source PCR machine for a few hundred dollars. Some kids have made them even cheaper.
Once you have duplicated your sample a sufficient amount you then use a specially prepared tag that is made using information about what you want to test for (in the current case, genetic material of Ebola*). Getting the right tag is the key issue in the case of Ebola.
Then there are a few possible approaches to take, any of which should be relatively quick (a few minutes). All are basically using the specially prepared tag as a lure of sorts and seeing if the tag binds to anything in the sample. If so, the test is positive for Ebola.
*OK, technically Ebola has RNA, not DNA. The tag may be a bit of DNA that binds to a sequence of RNA that is specific to the Ebola virus.
Or they may be running the entire initial sample through something called RT-PCR to make a complimentary DNA sequence. The tag would then bind to this complimentary DNA.