Just how long does the Ebola virus linger in semen?

The 2013-2016 West African Ebola virus outbreak altered our perception of just what an Ebola outbreak could look like.

While none of the three primary affected countries–Liberia, Sierra Leone, and Guinea-have had a case since April 2016, the outbreak resulted in a total of over 28,000 cases of Ebola virus disease (EVD)–65 times higher than the previous largest EVD outbreak, and more than 15 times the total number of cases of all prior EVD outbreaks combined, from the virus’s discovery in 1976 to a concurrent (but unrelated) outbreak in the Democratic Republic of Congo in 2014.

In March 2016, cases were identified once again in both Liberia and Guinea, just after the outbreak had been declared over. Both countries were declared Ebola-free in June 2016; Guinea for the second time and Liberia for the fourth time. The last series of cases in these countries demonstrated just how different this epidemic was from prior ones, changing what we thought we knew about the virus:

Previous research suggested Ebola could persist in the semen for 40 to 90 days. But that window has been eclipsed in this epidemic by a considerable amount. A probable case of sexual transmission occurred approximately six months after the patient’s initial infection last year in Liberia. Another study found evidence of Ebola in the semen of 25% of surviving men tested seven to nine months after infection. And it takes only a single transmission to kick off a fresh recurrence of the disease.

A recent paper extended this window of virus persistence in the semen even longer–over 500 days. It also explains how the outbreaks began in both countries after being declared Ebola-free–so where did the virus come from?

In a convergence of old-fashioned, “shoe leather” epidemiology/tracing of cases and viral genomics, two converging lines of evidence led to the identification of the same individual: a man who had been confirmed as an EVD case in 2014, and had sexual contact with one of the new cases. Author Nick Loman discussed via email:

The epidemiologists told us independently that they had identified a survivor and we were amazed when we decoded the metadata to find that case was indeed the same person. The sequencing and epidemiology is tightly coordinated via Guinea’s Ministry of Health who ran National Coordination for the Ebola outbreak and the World Health Organisation.

It shows that the genomics and epidemiology works best when working hand-in-hand. If we’d just had the genomics or the epidemiology we’d still have an element of doubt.

The sequencing results also suggested that it was likely that the new viral outbreak was caused by this survivor, and unlikely that the outbreak was due to another “spillover” of the virus from the local animal population, according to author Andrew Rambaut:

If the virus was present in bats and jumped to humans again in 2016, it might be genetically similar to the viruses in the human outbreak but not have any of the mutations that uniquely arose in the human outbreak (it would have its own unique mutations that had arisen in the bat population since the virus that caused human epidemic).

It might be possible that the virus jumped from humans to some animal reservoir in the region and then back to humans in 2016 but because we have the virus sequence from the patients acute disease 15 months earlier we can see that it essentially exactly the same virus. So this makes it certain the virus was persisting in this individual for the period.

So the virus–persisting in the survivor’s semen for at least 531 days–sparked a new wave of cases. Ebola researcher Daniel Bausch noted elsewhere that “The virus does seem to persist longer than we’ve ever recognized before. Sexual transmission still seems to be rare, but the sample size of survivors now is so much larger than we’ve ever had before (maybe 3,000-5,000 sexually active males versus 50-100 for the largest previous outbreak) that we’re picking up rare events.”

And we’re now actively looking for those rare events, too. The Liberia Men’s Health Screening Program already reports detection of Ebola virus in the semen at 565 days following symptoms, suggesting we will need to remain vigilant about survivors in both this and any future EVD epidemics. The challenges are clear–we need to investigate EVD survivors as patients, research participants, and possible viral reservoirs–each of which comes with unique difficulties. By continuing to learn as much as we can from this outbreak, perhaps we can contain future outbreaks more quickly–and prevent others from igniting.

Zika: what we’re still missing

As you’ve probably seen, unless you’ve been living in a cave, Zika virus is the infectious disease topic du jour. From an obscure virus to the newest scare, interest in the virus has skyrocketed just in the past few weeks:

 
I have a few pieces already on Zika, so I won’t repeat myself here. The first is an introductory primer to the virus, answering the basic questions–what is it, where did it come from, what are its symptoms, why is it concerning? The second focuses on Zika’s potential risk to pregnant women, and what is currently being advised for them.

I want to be clear, though–currently, we aren’t 100% sure that Zika virus is causing microcephaly, the condition that is most concerning with this recent outbreak. The circumstantial evidence appears to be pretty strong, but we don’t have good data on 1) how common microcephaly really was in Brazil (or other affected countries) prior to the outbreak. Microcephaly seems to have increased dramatically, but some of those cases are not confirmed, and others don’t seem to be related to Zika; and if Zika really is causing microcephaly, 2) how Zika could be causing this, whether timing of the infection makes a difference, and whether women who are infected asymptomatically are at risk of medical problems in their developing fetuses.

The first question needs good epidemiological data for answers. This can be procured in a few ways. First, babies born with microcephaly, and their mothers, can be tested for Zika virus infection. This can be looked at a few ways: finding traces of the virus itself; finding antibodies to the virus (suggesting a past infection–but one can’t know the exact timing of this); and asking about known infections during pregnancy. Each approach has advantages and limitations. Tracking the virus or its genetic material is a gold standard, but the virus may only be present in body fluids for a short time. So if you miss that window, a false negative could result. This could be coupled with serology, to look at past infection–but you can’t be 100% certain in that case that the infection occurred during pregnancy–though with the apparently recent introduction of Zika into the Americas, it’s likely that infection would be fairly recent.

Serology coupled with an infection in pregnancy that has symptoms consistent with Zika (headache, muscle/joint pain, rash, fever) would be a step up from this, but has some additional problems. Other viral infections can be similar in symptoms to Zika (dengue, chikungunya, even influenza if the patient is lacking a rash), so tests to rule those out should also be done. On the flip side, about 80% of Zika infections show no symptoms at all–so a woman could still have come into contact with the virus and have positive serology, but she wouldn’t have any recollection of infection.

None of this is easy to carry out, but needs to be done in order to really establish with some level of certainty that Zika is the cause of microcephaly in this area. In the meantime, there are a few other possibilities to consider: that another virus (such as rubella) is circulating there. This is a known cause of multiple congenital issues, including microcephaly. This could explain why they’re seeing cases of microcephaly in Brazil, but none have been reported thus far in Colombia. Another is that there is no real increase in microcephaly at all–that, for some reason, people have just recently started paying more attention to it, and associated it with the Zika outbreak in the area–what we call a surveillance bias.

This is a fast-moving story, and we probably won’t have any solid answers to these questions for some time. In the interim, I think it’s prudent to take this as a possibility, and raise awareness of the potential this virus *may* have on the developing fetus, so that women can take precautions as they’re able. Public health is about prevention, and there have certainly been cases in the past of links between A and B that fell apart under further scrutiny. Zika/microcephaly may be one, but for now, it’s an unfortunate case where “more research is needed” is about the best answer one can currently give.

Why quarantine for measles is critical…and quarantine for Ebola was not

Measles has come to the happiest place on Earth. As of this writing, a total of 32 cases of measles have been linked to Disneyland visits that took place between December 17th and 20th. About 75% of the cases identified to date were not vaccinated, either because they chose to forgo vaccines or because they were too young, and at least 6 have been hospitalized.

A measles outbreak is a public health disaster, which can cost into the millions of dollars in health resources. You can be sure that public health workers in California and beyond are working overtime trying to identify cases, educate those who were possibly exposed about how dangerous measles can be, and implement practices so that those who may have been exposed to measles don’t further put others at risk. This includes avoiding public places, and practices such as calling ahead to a doctor’s offices so possible cases can be ushered into private rooms rather than languishing in the waiting room. A clinic in La Mesa recently closed because of a potential measles exposure. An unvaccinated South Pasadena woman, Ylsa Tellez, received a quarantine order after her younger sister was diagnosed with measles. Tellez is fighting the order and “taking immune-boosting supplements” instead.

Why such extreme measures on the part of public health?

Measles is highly contagious. It’s spread by air, and so contagious that if an infected person enters a room, leaves, and an unvaccinated person enters the room hours later, they still can contract measles. Remember a few months back, when that figure was circulating showing that Ebola wasn’t particularly easy to spread? Well, measles very much is. The basic reproductive rate for Ebola is around 2, meaning on average each infected person will cause an additional 2 infections in susceptible individuals.

And what’s the reproductive number for measles?

Eighteen. Eight. Teen. I’m not exaggerating when I say that it is literally one of the most contagious diseases we know of.  On average, if you have 10 susceptible individuals exposed to a measles patient, 9 will end up getting sick.

How do we break the cycle of transmission? Vaccination is one way–if one has been vaccinated for measles, chances are very low (but not zero, because nothing is perfect) that they will contract measles. Beyond vaccination, the next-best intervention is to keep those who are infected away from everyone else. The way we do this is by quarantining them.

In public health terms, quarantine specifically refers to the separation of individuals who have been exposed to an infectious agent, *but are not yet ill themselves,* from the rest of society. That way, they’re unable to spread the infection to others. Quarantine makes the most sense when individuals can transmit the infection before they realize they’re sick, which is exactly the case with measles. Infected individuals can spread the virus fully 4 days before the characteristic rash starts to appear, and continue to spread it for another 4 or so days after the rash begins—potentially infecting a lot of people. The problem is, like Ylsa Tellez, they’ll feel fine while they’re out there in the general population. They don’t even have to be coughing or sneezing to spread it (symptoms which can appear prior to the rash)—they can just be breathing (something many of us like to do on a regular basis), and still contaminate their environment with the measles virus.

The difference in transmissibility also makes measles a very different situation from Ebola. Public health officials almost universally condemned quarantine for Ebola exposures, for two reasons: 1) Ebola wasn’t highly transmissible, and  isn’t airborne like measles is; and 2) because Ebola isn’t efficiently transmitted until late in the infection when the patient is very ill and likely bedridden. Quarantining Ebola patients was a political stunt, not a public health necessity.

This is why states have the legal authority to enforce quarantine for infectious diseases: it reduces the risk that asymptomatic, potential disease-spreaders will act as “Typhoid Marys” (another asymptomatic, deadly-disease-spreader), which is in the public interest. And while unvaccinated Tellez feels “attacked” and her mother thinks people are being “not nice” when they demand that Tellez submit to quarantine, their choice not to vaccinate has already put many others at risk of disease and, and is resulting in the quarantine of many other exposed individuals as well. In the 2011 Utah measles outbreak, 184 were quarantined and thousands of contacts traced, at an expense of approximately $300,000. The Disneyland outbreak has already spread into 4 states (California, Utah, Washington, and Colorado). Quarantine is one of our tools to stem the epidemic. In our recent outbreak among Ohio Amish, most willingly submitted to quarantine, and over 10,000 doses of the MMR vaccine were administered. Quarantine is undoubtedly a difficult prospect to face, but perhaps if Tellez and others had been vaccinated in the first place, they, and we, wouldn’t be in this situation.

Ebola fears at Kent State

Though I haven’t had a chance to write about this here, I have an article at Mic.com on Kent’s experience with Ebola exposure in our area. Amber Vinson, the second Ebola-infected nurse in Texas, is a Kent State alumna and has relatives that work here. Our experience on campus so far is described here in this article.

New paper on Ebola–no primate-to-primate transmission seen

By the same lead author that published the pig Ebola transmission paper comes a new publication examining airborne transmission among primates. In these, Ebola did *not* spread between non-human primates (NHPs) via air. I sent an email to the PI to comment; will update the post if he responds, but in the meantime, some money quotes directly from the publication:

“One experiment reported contact free transmission between infected NHPs to one uninfected NHP although cross-contamination due to husbandry practices could not be ruled out with certainty26. Interestingly, EBOV infected swine transmitted the virus to naïve NHPs over a 0.3 meter buffer zone that prevented direct contact between the 2 species27. …However, airborne transmission in natural outbreaks cannot be a common occurrence and is possibly insignificant by the account of several reports49282930.”

and

“The presence of transmission in the pig-NHP experiment and not the NHP-NHP experiment, both performed under similar conditions and environments, could be explained by the fact that EBOV disease in pigs is respiratory in nature with high amounts of infectious particles present in the oro-nasal cavities in the symptomatic phase of the disease which provided an opportunity for release into the environment35. On the receiving end, NHPs are known to be susceptible to lethal EBOV infection through the respiratory tract242731 putting the onus of the transmission on the ability of the source to shed infectious particles.”

Translation: even though previous reports in primates had suggested the potential for airborne transmission, other factors couldn’t be ruled out, and epidemiologically, it’s insignificant. In the experiments they did, pigs just handle Ebola differently than primates (as I mentioned here), and so make them more likely to spread the virus via a respiratory route.

Significance: No airborne transmission between primates in this controlled experiment, strengthening the evidence that Zaire ebolavirus isn’t a risk in this manner. So Donald Trump, you can stop freaking out now.

A historical perspective on Ebola response and prevention

Yambuku, Zaire, 1976. A new disease was spreading through the population. Patients were overcome by headaches and bloody diarrhea. The disease was spreading through entire families and wiping them out.

Eight hundred and twenty-five kilometers to the northeast, a similar epidemic was reportedly raging across the border in Maridi, Sudan. Were these outbreaks connected? Despite enormous challenges trying to navigate both the logistics of crossing a landscape of unpaved and unmarked roads, as well as the political difficulties of an attempt to enter and collect samples in an area marked by recent civil strife, samples were finally collected and shipped to the World Health Organization for testing.

All told, these outbreaks caused 602 cases and 431 deaths. The Zaire outbreak wasn’t stopped until the hospital was closed, because 11 of its 17 workers (65%) had died of the disease. Investigators went door-to-door in 550 villages in the Yambuku area  to find and isolate new cases. Roadblocks were set up to restrict access to the area.

In Sudan, a number of cases were traced to workers in a cotton factory (probably due to bat exposure) and their families. The epidemic increased when one case went to the Maridi hospital, and the virus then was transmitted within that hospital. Note what the write-up describes:

“The hospital served as an efficient amplifier from which the virus was disseminated throughout the town. The number of cases gradually increased until mid-September and at the end of the month there was a large number of cases, particularly in hospital staff. The number of cases declined in early October, possibly as a result of the use of protective clothing. A considerable increase in the number of cases was observed in late October and early November, which may have been partly due to a lack of protective clothing when supplies ran out in mid-October.”

In Maridi, the doctor-in-charge, along with 61 members of the nursing staff came down with Ebola. Thirty-three of them died. Eight additional deaths occurred among the ancillary and cleaning staff. This outbreak was only contained because, again, the hospital was made safer via extensive training and the use of good personal protective equipment, and cases were identified in the town by going door-to-door. Buy-in from local officials was obtained, which is critical–while families may not trust outsiders, they more often will listen to local leaders. Cases were isolated in their homes or taken to the hospital. Eventually every village in a 30-mile radius from Maridi was screened, and the outbreak burned out.

Now imagine you’re looking at this in real time, via 24-hour news networks, from halfway across the world. You’re hearing news reports of cases spiking. Healthcare workers are contracting the disease. You don’t have all the information but you’re coming to your own conclusion that the virus must be mutating in Sudan.

You would, however, be wrong. These outbreaks were actually separate epidemics (and led to the identification of Zaire ebolavirus and Sudan ebolavirus, respectively), but collectively, that was a lot of Ebolavirus disease in 1976–the most deadly single year for Ebola until 2014, in fact. It took an enormous effort on the ground in these two areas to stop the outbreak.

Though not wholly analogous to today’s West African epidemic, there are lessons here to take away. There is a steep learning curve for dealing with Ebola. Besides the single case from the Ivory Coast, Ebola has not historically been a West African disease. Liberia, and Guinea and Sierra Leone in particular, do not have a great history of governmental stability, and are still recovering from civil wars, government coups, and a general lack of stable national leadership. Infrastructure is also substandard, as early reports on the main hospital in Conakry, Guinea noted. Each country seems to be dealing with this largely on their own without solid cross-border cooperation, and since the borders tend to be flexible in any case, patients and those incubating Ebola have been able to travel and move the virus into new areas. The public in general does not understand the disease, and in some cases keeping doctors out with knives and machetes, accusing physicians of murdering their loved ones and bringing Ebola to their villages.

It’s reasons like this–structural and sociological issues, by and large–that have led the WHO to declare the outbreak to be “out of control.” As far as has been reported, there is nothing particularly notable about the virus itself, which is very closely related to previous Zaire ebolavirus isolates. The infection rate in healthcare workers–about 60 out of 1300 total cases reported at the time–is actually quite low, given the conditions they’re working in and the lack of experience most of them would have had with Ebola. (Again, in Sudan, it was 61 out of 284 cases–so 21% of the total cases were doctors and nurses–versus about 5% in this outbreak).

The outbreaks in these countries are bad currently, but for the future, we can look at Uganda as a model. The first outbreak in that country, beginning in 2000, resulted in 425 cases and 224 deaths. The second outbreak in 2008 resulted in 149 cases and 37 deaths. In 2011, they had a single case with no secondary spread. In 2012, 11 cases and 4 deaths. 2012, 6 cases and 3 deaths. It’s probably impossible to stop Ebola from spilling over into the human population, but Uganda has done a great job responding. They are able to do early detection of suspected cases in their biosafety level 4 lab in Gulu. They alert local authorities if something is suspected, then send a task force to assist with containment. They communicate effectively with the public about what they can do, and how effective treatment in hospitals can lower the mortality rate. They work with community leaders when a quarantine needs to be put in place. These things can all be employed in West Africa as well, but it takes time and a lot of commitment to get such networks up and running. We need this cooperation as much as we need PPE and even more than we need “secret serums,” because it is only with prevention of new cases that this epidemic will finally die out.

 

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Are we *sure* Ebola isn’t airborne?

Since yesterday’s post, several people have asked me on various social media outlets about the airborne nature of Ebola. Didn’t I know about this paper (“Transmission of Ebola virus from pigs to non-human primates“), which clearly showed that Ebola could go airborne?

Indeed I do–I wrote about that paper two years ago, and it in no way changes my assertion that Ebola doesn’t spread between people in an airborne manner.

Let me back up. The paper in question was an experimental study done in the wake of the 2008 finding of the Reston Ebola virus in pigs and a previous study looking at the Zaire virus in pigs. In the air transmission study, they inoculated pigs with Ebola and examined transmission to macaques (who were not in direct contact with the infected pigs). They did find aerosolized Ebola in air samples, and some of the macaques did come down with symptoms of Ebola. So, it looked like pigs could spread Ebola through the air, which is something that had already been suggested by the epidemiology of the 2008 pig Ebola outbreak. It’s always nice when experimental data matches up with that observed during a real-life occurrence of the virus.

*However*, the kicker was not that Ebola is transmitted by air in human outbreaks, but rather that there may be something unique about pig physiology that allows them to generate more infectious aerosols as a general rule–so though aerosols aren’t a transmission route between primates (including humans, as well as non-human primates used experimentally), pigs may be a bigger threat as far as aerosols. Thus, this may be important for transmission of swine influenza and other viruses as well as Ebola.

So unless you’re sitting next to an Ebola-infected pig, seriously, airborne transmission of Ebola viruses isn’t a big concern. (Perhaps this corollary should be added to this handy diagram examining your risk of Ebola).

 

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Ebola is already in the United States

It’s odd to see otherwise pretty rational folks getting nervous about the news that the American Ebola patients are being flown back to the United States for treatment. “What if Ebola gets out?” “What if it infects the doctors/pilots/nurses taking care of them?” “I don’t want Ebola in the US!”

Friends, I have news for you: Ebola is *already* in the US.

Ebola is a virus with no vaccine or cure. As such, any scientist who wants to work with the live virus needs to have biosafety level 4 facilities (the highest, most secure labs in existence–abbreviated BSL4) available to them. We have a number of those here in the United States, and people are working with many of the Ebola types here. Have you heard of any Ebola outbreaks occurring here in the US? Nope. These scientists are highly trained and very careful, just like people treating these Ebola patients and working out all the logistics of their arrival and transport will be.

Second, you might not know that we’ve already experienced patients coming into the US with deadly hemorrhagic fever infections. We’ve had more than one case of imported Lassa fever, another African hemorrhagic fever virus with a fairly high fatality rate in humans (though not rising to the level of Ebola outbreaks). One occurred in Pennsylvania; another in New York just this past April; a previous one in New Jersey a decade ago. All told, there have been at least 7  cases of Lassa fever imported into the United States–and those are just the ones we know about, who were sick enough to be hospitalized, and whose symptoms and travel history alerted doctors to take samples and contact the CDC. It’s not surprising this would show up occasionally in the US, as Lassa causes up to 300,000 infections per year in Africa.

How many secondary cases occurred from those importations? None. Like Ebola, Lassa is spread human to human via contact with blood and other body fluids. It’s not readily transmissible or easily airborne, so the risk to others in US hospitals (or on public transportation or other similar places) is quite low.

OK, you may say, but Lassa is an arenavirus, and Ebola is a filovirus–so am I comparing apples to oranges? How about, then, an imported case of Ebola’s cousin virus, Marburg? One of those was diagnosed in Colorado in 2008, in a woman who had traveled to Uganda and apparently was sickened by the virus there. Even though she wasn’t diagnosed until a full year after the infection (and then only because *she* requested that she be tested for Marburg antibodies after seeing a report of another Marburg death in a tourist who’d visited the same places she had in Uganda), no secondary cases were seen in that importation either.

And of course, who could forget the identification of a new strain of Ebola virus *within* the United States. Though the Reston virus is not harmful to humans, it certainly was concerning when it was discovered in a group of imported monkeys. So this will be far from our first tango with Ebola in this country.

Ebola is a terrible disease. It kills many that it infects. It *can* spread fairly rapidly when precautions are not carefully adhered to: when cultural practices such as ritual washing of bodies are continued despite warnings, or when needles are reused because of a lack of medical supplies, or when gloves and other protective gear are not available, or when patients are sharing beds because they are brought to hospitals lacking even such basics as enough beds or clean bedding for patients. But if all you know of Ebola is from The Hot Zone or Outbreak, well, that’s not really what Ebola looks like. I interviewed colleagues from Doctors without Borders a few years back on their experiences with an Ebola outbreak, and they noted:

“As for the disease, it is not as bloody and dramatic as in the movies or books. The patients mostly look sick and weak. If there is blood, it is not a lot, usually in the vomit or diarrhea, occasionally from the gums or nose. The transmission is rather ordinary, just contact with infected body fluids. It does not occur because of mere proximity or via an airborne route (as in Outbreak if I recall correctly). The outbreak control organizations in the movies have no problem implementing their solutions once these have been found. In reality, we know what needs to be done, the problem is getting it to happen. This is why community relations are such an issue, where they are not such a problem in the movies.”

So, sure, be concerned. But be rational as well. Yes, we know all too well that our public health agencies can fuck up. I’m not saying there is zero chance of something going wrong. But it is low. As an infectious disease specialist (and one with an extreme interest in Ebola), I’m way more concerned about influenza or measles many other “ordinary” viruses than I am about Ebola. Ebola is exotic and its symptoms can be terrifying, but also much easier to contain by people who know their stuff.

 

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