For the first time, a suspected Ebola case has appeared in the Congo’s conflict zone. A doctor in the town of Oicha, in North Kivu province, is strongly suspected of being infected, despite having initially tested negative for the virus.  “Oicha is almost entirely surrounded by ADF Ugandan Islamist militia, and there are ‘extremely serious security concerns’ following many civilian killings,” according to WHO’s head of emergency operations.  Africa News, Aug. 24, 2018.

It’s hard enough to contain Ebola in normal conditions. There is reason for concern that the strategies that eventually worked in West Africa may not be able to stop an epidemic in a conflict zone.

There’s also good news, however: Two of the first ten recipients of the mAb114 treatment have recovered. This is one of five five experimental treatments Congo approved for use in the outbreak that was declared on Aug. 1.  Washington Post, Aug. 25, 2018.

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Fully recovered Ebola patients are in general no longer infectious, but there are exceptions.

Isolated cases have long been reported if virus persisting in the eye and in sperm. Now there is a definitive study showing both persistence and active infectiousness in sperm at least 2-1/2 years after recovery, with no reason to think that infectiousness might not continue indefinitely. https://www.sciencesetavenir.fr/sante/ebola-le-sperme-peut-proteger-le-virus-pendant-2-5-ans_125545

From a public health standpoint the sperm of recovered patients is a reservoir from which Ebola disease can re-emerge into the population. This isn’t a huge deal since periodic recurrences were already to be expected from animal reservoirs. It is of concern, however, that outbreaks from sperm infection would likely occur in densely populated areas rather than in the remote jungle villages that are most exposed to wild animals. It also means that countries with no animal reservoirs, and no experience with Ebola, could have outbreaks arising from a visiting or migrating survivor. A sexually active survivor could unknowingly infect multiple partners over an extended period since he himself will not fall ill. Public health agencies need to be vigilant to identify and snuff out any new outbreaks stemming from this source. On the other hand, the lack of such outbreaks so far is somewhat reassuring.

Testing of male survivors might allow concern to be lifted from some and focused on others. Surviving males, unless definitively tested negative, should be strongly encouraged to use condoms. They and their partners should be encouraged to promptly report any suspicious symptoms (though the same pattern of fear and denial is likely to recur in future outbreaks). The right of survivors to medical privacy will be in tension with public health concerns. Survivors known or suspected to be infected could be unfairly ostracized and stigmatized.

Ebola is endemic in the Congo but previously was confined to remote places where it could be rather easily snuffed out. Now it has reached a major city. Cross your fingers that it can be stopped.

Update June 28, 2018: Rapid response and deployment of a new vaccine contained the outbreak, as reported in the New York Times. More than 3,200 people — contacts and health providers — were vaccinated, and none fell ill. As reported in the article, 29 died out of 53 confirmed or probable Ebola cases. This outbreak began in a remote village, presumably from bush meat or other contact with infected wild animals.

Great News From Liberia

The news from Liberia is wonderful: the last known Ebola patient has been discharged from treatment! [NYT 3/6/15] This doesn’t make Liberia “Ebola free” – that requires 42 days (twice the incubation period) with no new cases. Many contacts are still being monitored, and others may not have been identified, so Liberia may still have to deal with a few more local outbreaks before it can declare victory. Also, so long as Ebola continues in neighboring countries the disease may be brought back to Liberia by travelers (though note this heartening item about an effective Liberian border control operation: [IOM 2/4/15]). And the risk of an unrelated jump to a human from an animal reservoir will continue indefinitely. Nevertheless, this is a moment to be savored!

Update 3/24/15: A new patient has been identified in Liberia, who probably was infected by her boyfriend, an Ebola survivor. [NYT 3/24/15]. This is disappointing, but the fact that only one instance has come to light suggests that this mode of transmission is rare.

Ongoing Transmission in Sierra Leone and Guinea

Sierra Leone initially showed a similar pattern of precipitous decline in patients, but since the end of January weekly cases have stabilized between 60 and 100. [WHO 3/4/15] This is better than exponential growth, but it’s not on track to ending the epidemic. Guinea didn’t have as sharp a peak, but it also hasn’t experienced such a dramatic improvement: about 50 cases are continuing to arise each week. In both countries the steady rate of new cases implies an Effective Reproduction Rate of about 1. Pushing this down just a little would eventually end the epidemic, while letting it rise would allow exponential growth to resume. Liberia has shown that it’s possible to snuff out the epidemic, but Sierra Leone and Guinea are not yet following in Liberia’s footsteps.

I don’t claim to know how Liberia did it, but somehow the Effective Reproduction Rate dropped to about 1 in September, then fell much lower from October on. Sierra Leone’s peak and fall were similar, but occurred about two months later, and the decline has now leveled out. While the opening of new treatment centers certainly helped in recent months, my own best guess is that the main factor in both countries is that people simply “got religion.” That is, a large enough fraction of Liberians came to accept that Ebola is caused by a virus, not a curse; that people who fall ill need to be cared for in safe settings, rather than at home; and that corpses need to be handled with extreme care. I suppose that a comparable fraction of Sierra Leone’s population reached similar conclusions, but the epidemic is now continuing there and in Guinea within sub groups that haven’t fully accepted the message.

Devilish Details

The last Ebola patient in Liberia, Beatrice Yardolo, came from a worrisome cluster of cases “in a community called St. Paul’s Bridge, located in what was one of the biggest Ebola hot spots in Monrovia, New Kru Town.” [NYT 3/6] The New York Times reported that, “[t]he outbreak was unusually violent and far-reaching, in part because it involved criminal gangs that did not cooperate with the authorities and fears that it could be spread through a knife fight with one member nicknamed Time Bomb.” Even more troubling was the fact that known contacts on several occasions left Monrovia for other parts of the country. [FrontPageAfrica 2/3/15] One of the escaped contacts died in Margibi County, and required the tracking of 256 contacts there. [GNN Liberia 2/4/15]

Ebola came into the Yardolo family from Beatrice’s cousin Steve, who probably became infected at an Ebola treatment center where he worked. [AllAfrica 3/6/15]  Steve infected several other members of the family, eventually including his daughter Amanda. Beatrice took responsibility for Amanda’s care, but again and again Amanda was mis-diagnosed and rejected from Ebola treatment centers. Beatrice was left responsible for bathing and otherwise caring for her. After Amanda died Beatrice went immediately to a treatment center started showing symptoms, which probably saved her life.

Ebola didn’t end in Liberia because people behaved well, but because the strategies of isolation and contact tracing worked despite much bad behavior and many mistakes.

Sierra Leone’s experience is vividly described in another New York Times piece. [NYT 2/18/15] The epidemic was re-ignited by three sick fishermen who landed in a poor area of Freetown in early February. Two dozen people in the area ended up contracting Ebola from this initial group before transmission was brought under control. A quarantine was imposed but was frequently broken. One shopkeeper fell ill but was afraid to go to a hospital in Freetown. Instead he broke quarantine and traveled three hours to his home village, where he visited a traditional healer, then died. He caused the infection of some 42 people in the district.

Endemic Ebola?

Ebola is still being actively transmitted in Sierra Leone and Guinea, and may yet recur in Liberia, or spread to other countries. But the Liberian experience gives every reason to hope that the techniques that worked there can eventually end this epidemic altogether. The possibility must be acknowledged, however, that the epidemic will continue indefinitely, neither growing exponentially nor definitively ending. In this case Ebola would become “endemic” to West Africa — just one of the typical diseases that people get there. I can’t disprove this — indeed it seems to be happening now in Guinea — but I have several reasons for doubting that this will happen with the current strain of Ebola:

  • It’s too deadly. A cluster of a less lethal disease might go relatively unnoticed, but this can’t happen with Ebola. The deaths of family and friends, one after another, cannot be ignored. The presence of Ebola in a community will not be tolerated for long.
  • Its incubation period is too short. A disease that takes months or years to emerge (e.g. AIDS, leprosy, tuberculosis) can hide in a human population, but Ebola emerges quickly, or not at all.
  • It’s only transmitted from person to person. Aside from the wild animal reservoir (discussed below) Ebola appears to be transmitted only from person to person. A disease that could also infect some more familiar animal, like fleas or rats, could hide in the animal reservoir and reemerge unpredictably. Fortunately, Ebola shows no sign of doing this.
  • It’s only transmitted by direct contact. Fortunately, Ebola isn’t airborne; it’s transmitted only by direct contact with bodily fluids or contaminated surfaces. This makes contact tracing and isolation so effective. It’s much more difficult to contain a disease like the flu that spreads through the air.
  • People are infectious only when they are ill.  Update 3/24/15: (except for the semen of male survivors). There is no indication that there are “Typhoid Marys” who can transmit Ebola without themselves falling ill, except for one instance in which a male survivor appears to have infected his partner, presumably through semen, which is known to contain Ebola virus for several months after recovery. [NYT 3/24/15] This will make the disease a bit more difficult to eradicate, but is not cause for panic. As noted above, the fact that just one infection of this type has come to light suggests that this mode of transmission is infrequent. Additionally, now that an example exists one might expect many “discordant couples” (in which the male is a survivor and the female is not) to use condoms, which should further reduce the risk. One question that calls for further research is how long the virus can persist in the semen of a male survivor, and whether a negative semen test is sufficient to make unprotected intercourse safe for the survivor’s partners.

For these reasons I think it’s highly unlikely that Ebola will become endemic based on human-to-human transmission (absent mutation). So long as we don’t lose focus I expect that Sierra Leone, and eventually Guinea, will be able to end this epidemic using the standard techniques of contact tracing, isolation, funeral management and education.

The Wild Animal Reservoir

In one important respect Ebola already is endemic to East Africa: For forty years it has jumped every few years from its wild animal reservoir (probably fruit bats) into a human population. Just this year an unrelated Ebola outbreak in a rural area of Uganda flared briefly and was extinguished. [CDC]  There is every reason to expect this pattern to continue, since:

  1. even when we have a vaccine it will never be feasible to vaccinate the entire relevant population,
  2. contact with infected animals such as bush meat may be reduced through education but can’t be prevented altogether, and
  3. there is no conceivable way to eliminate Ebola from the animal reservoir.

This is too bad, but it’s a bearable situation, since most outbreaks start in remote rural areas, where they can be quickly snuffed out so long as they are detected early and the response is competent and decisive.

So far as we know the West African epidemic arose from a single jump between a wild animal reservoir and a human. There might be some reason why this was an isolated incident that won’t recur. But it seems much more likely that Ebola is now established in a West African animal reservoir, from which it will now jump periodically into humans, the same way it has for decades in East Africa. After the current epidemic is brought under control it will be essential for all West African countries to establish systems for early detection of new Ebola outbreaks, as has long been the case in East Africa.

We’re lucky that infective contacts between humans and the wild animal reservoir are so rare. If Ebola became established in an animal population that lived in closer contact with humans — rats, pigs, or even dogs — animal-human transmissions could be much more frequent. There is no evidence, however, that this is happening. Genetic evidence continues to indicate that the entire West African epidemic was sparked by a single animal-human transmission in Guinea, from a bat to a 2-year-old boy.

There are still great challenges and great dangers — more on that later — but the big news is the abatement of the epidemic in Liberia.

Miracle in Liberia

Here is WHO’s chart of new cases in the country as a whole, and in the Montserrado district (which includes the capital, Monrovia). [WHO Current Ebola Situation Report]

Liberia_New_Cases_20141203

The drop, starting in mid-September, is breathtaking, even when figures from the patient database are adjusted by more realistic situation reports. There is now a big oversupply of isolation beds in Monrovia, and in some other parts of the country. The ready availability of beds certainly contributed to the drop in new cases, but other factors must also be at work since the fall began while all available beds were still occupied. I speculated on the reasons for the apparent drop in my previous post: Too Good to be True? I don’t have much to add, except that behavior must have dramatically changed in Liberia. Changing people’s behavior is very hard, especially when it relates to deeply-rooted cultural norms such as caring for loved ones and religiously-mandated burial practices. The message from Liberia is that behavior change is possible, and it can stop Ebola (in its current form) in its tracks.

The magnitude of the change is dramatic. The Reproduction Rate (defined in The Ebola Chain Reaction) for Liberia had been estimated in September at 1.51 [NEJM 9/23/14] , which is consistent with the left half of the charts shown above — exponential growth. The right half of these curves implies a Reproduction Rate far below the steady state of 1.0, which means that the rate dropped by at least a factor of two in a period of just a few weeks. It’s marvelous that such a large change was possible in such a short time frame. This affords a solid basis to hope that the same can be accomplished in the other affected countries.

The epidemic is by no means over in Liberia! We must not let down our guard, or infection rates could jump up again. But we can certainly take heart. It might also be reasonable to mothball the construction of new isolation facilities in Monrovia, keeping open the option of finishing them if they are ever needed. To the extent possible, new facilities should be constructed in Sierra Leone and Guinea, or perhaps under-served parts of Liberia,  rather than in Monrovia.

Steady Rate in Guinea

The rate of new cases jumped dramatically around the end of August and has continued at more or less the same level. This is a continuing severe epidemic, with Reproduction Rate around 1, but it is growing slowly if at all.

Guinea_New_Cases_20141203

WHO’s helpful situation report breaks the results down by region and points out a particular vulnerability in the northern area adjacent to Mali, which may lead to further spread to that country.  [WHO Current Ebola Situation Report] This is still a desperate crisis, but the slow rate of growth gives us time to get ahead of the situation. And the example of Liberia shows that control is possible.

Exponential Growth in Sierra Leone

The big worry now is Sierra Leone, where the rate of new cases is continuing to grow exponentially.
Sierra_Leone_New_Cases_20141203

Growth in Sierra Leone is country-wide, but the capital of Freetown presents the most acute problem because it is running out of beds. Once again, the WHO situation report describes what’s happening and the management plan: [WHO Current Ebola Situation Report]  We just have to hope that the miracle in Liberia can be replicated in Sierra Leone.

Concluding Observations

Just a few weeks back Liberia was the greatest worry, and the focus was on building isolation facilities there, especially in Monrovia. Now many of those facilities stand empty. Like a wily prize fighter Ebola ducked the roundhouse punch we had planned for it there, and is continuing to fight in other parts of the ring. This doesn’t mean that our plans were mistaken, or even unnecessary, since nobody could have foreseen the dramatic drop in transmission in Liberia. But it does mean that we need to be nimble in responding to where the greatest need currently is — Sierra Leone and the northern districts of Guinea. The need to redeploy resources is problematic, since it takes time and effort to design, build and staff a new facility. We have no choice, however: we must follow the epidemic wherever it goes.

So long as there is active transmission we are still exposed to two big risk factors:

  • spread to another country with crowded slums, traditional practices and a weak healthcare system, and
  • mutation to become more contagious.

I’m optimistic at this point that we can control the epidemic before either of these disasters occurs, but the need to end Ebola is still urgent.

 

 

 

 

For months treatment centers in Monrovia have been turning away patients, who are then cared for at home, which places household members at high risk of infection. New treatment facilities have been filled as soon as they become available. Projections showed the need for ever increasing numbers of beds, for at least the next several months.

But suddenly, around the middle of October, reported cases and burials in Monrovia have started to drop. Some Ebola clinics are less than half full! [NYT 10/31/14]  [Economist 11/1/14] Can it be that the epidemic is waning? Or are appearances deceiving? On the same day Yale researchers warn that deaths could skyrocket, consistent with the earlier models of exponential growth. [Yale Daily News 10/31/14]

I don’t have a crystal ball, but I will just throw out a few ideas:

  • Home treatment kits started being distributed around the middle of October. [Reuters 10/20/14] This is a desperate stopgap, since patients become so highly contagious in the last stage of illness that caregivers and others in a household are likely to be infected. But is it possible that many people are using home treatment kits instead of taking patients to clinics? If so, the epidemic could be roaring ahead unnoticed. Except for this: where are the burials? To make sense of this hypothesis you would have to also assume that families were secretly burying their dead members (thus creating more opportunities for infection). While this has been reported it seems implausible that it would occur widely enough to impact statistics, especially in an urban context.
  • More hopefully, the worst Reproduction Rate seen for Ebola in this epidemic was 2.2, which, though ample to fuel exponential growth, is not that much above the steady-state level of 1.0. (See my earlier post for details). Also, transmission of Ebola is a function of human behavior: primarily incautious care-giving and the handling of dead bodies. It’s difficult to change people’s behavior but the crisis in Liberia may just have been sufficiently acute for this to happen. Many individual decisions just may have added up to success: not to touch someone who seems ill; to use a barrier when touch is necessary; to sterilize objects with chlorine bleach; to allow a body to be taken away without traditional cleaning and funeral rites.
  • This report is from Monrovia, the capital of Liberia. We must not lose sight of what’s happening in other parts of Liberia, and in the other countries with active transmission: Guinea, Sierra Leone, and now quite possibly Mali.

Meanwhile, a new 200-bed treatment unit opened on October 31 in Monrovia. This is a big addition to the 500 beds previously available. “The daily management of the treatment centre will be taken care of by the Liberian Ministry of Health and Social Welfare, with support from African Union and Cuban foreign medical teams.” [WHO 10/31/14] I hope it is never needed, and that unused Ebola facilities may perhaps become the nucleus of an improved ongoing healthcare system in these desperately poor countries.

Ebola Resources

Ebola’s mortality rate may depend on several factors:

  • The particular strain of Ebola.
  • The age and underlying health of the patient.
  • How ill the patient is when s/he begins receiving care.
  • The quality of the care the patient receives.
  • The availability of antibody treatments such as ZMAPP or serum taken from survivors.

Prior Outbreaks

Before this year most Ebola outbreaks have been confined to rural areas, and treatment has been what was feasible in a tent. The West African epidemic is of the Ebola Zaire strain, for which WHO reports mortality rates from prior epidemics ranging from 44% to 90%. [WHO 9/14]

West Africa

It was initially thought that the mortality rate for the West African epidemic was around 55%. [Reuters 8/5/14]  In September, however, a scholarly article in the New England Journal of Medicine calculated the mortality rate in Guinea, Liberia and Sierra Leone at around 70%. [NEJM 9/23/14]  A Sierra Leone study of 44 patients [Reuters 10/29/14] showed 74% overall mortality, but broke the figure down in illuminating ways:

  • 57% of people under age 21 died, compared to 94% of those over the age of 45. Older patients have greater mortality risk.
  • 33% of patients with less than 100,000 copies of the virus per milliliter of blood at diagnosis ultimately died, compared with 94% of those whose had more than 10 million copies per milliliter. As we’ve previously suspected, mortality is highly dependent on how sick a patient is when treatment starts.

A thrilling anecdote from Liberia is also suggestive: A student nurse named Fatu Kekula cared for four household members, and managed to save three of them, achieving a 25% mortality rate. [LA Times 10/6/14]  She avoided infection herself using a resourceful combination of surgical gloves, plastic bags, raincoats and copious amounts of chlorinated water. Critically, she was able to give them IV drips, and she was on call essentially 24/7. What happened to any four patients has no statistical significance, but the demonstration that such a good outcome is even possible is heartening.

Nigeria

Nigeria had an outbreak sparked by a single air traveler from Liberia. Despite many high-risk contacts — and many incidents of quarantine-breaking and other misconduct — in the end there were only 19 cases, of which 7 died, for a mortality rate of just 37%. [WHO c.10/15/14] The number of cases is small, so this figure isn’t too statistically significant. One may speculate, however, that the lower mortality rate in Nigeria reflects two main factors: (1) better quality of health care, and (2) the fact that many patients were being monitored daily, so were presumably given care as soon as they began showing symptoms. The single patient who traveled to Senegal survived, and the child who traveled to Mali died, but neither case tells us anything about overall mortality rates.

The U.S. and Europe

The number of cases treated in western countries is also small, so even less statistically meaningful than the figure for Nigeria. As in Nigeria, most of these patients received treatment as soon as symptoms were noticed, which may be a significant benefit. Disregarding patients still in treatment, the figures, from the excellent New York Times Ebola Facts page, are as follows:

  • United States: 8 patients, of which 1 died and 7 recovered, for a mortality rate of 13%.
  • Europe: 8 patients, of which 3 died and 5 recovered, for a mortality rate of 38%.

Since the figures are so small the difference between Europe and the U.S. could easily be random. But it’s interesting to note that Thomas Eric Duncan, the patient who died in Dallas, had initially been turned away by the hospital, and only started receiving care after he had become so ill that he had to be transported by ambulance. His two nurses, in contrast, began receiving care soon after they first developed fevers, and both have recovered fully. CNN’s discussion of the factors that affect survival in western countries is a bit dated but still worth a look: [CNN 10/20/14]

Dr. Paul Farmer, a Harvard professor and co-founder of the charity Partners in Health, has expressed the hope that with top-notch care the mortality rate for Ebola could be as low as 10%. [London Review of Books 10/23/14] This isn’t inconsistent with the U.S. experience, keeping in mind the low sample number. It will be wonderful if it proves possible to substantially reduce the mortality rate in the African setting. An improved standard of care would not directly help stop the epidemic, but it would indirectly contribute to stopping transmission if it encouraged more people to enter clinics rather than staying at home, which increases the risk of infecting other household members.

Added 10/31/14: Paul Farmer’s emphasis on quality of care implicitly criticizes the way some twenty Ebola outbreaks have been handled since 1976, most notably by Médecins Sans Frontières / Doctors Without Borders (“MSF”). I would characterize the MSF approach as embodying three priorities:

1. Stop the Outbreak, by Isolating Patients.
2. Protect Staff from Getting Infected.
3. Cure as Many Patients as Possible.

For nearly 40 years MSF has been stunningly successful at achieving these goals, often in remote rural settings with extremely limited infrastructure. I’m sure Dr. Farmer would hasten to agree that we owe MSF and its peers an enormous debt of gratitude for their extraordinary service to humanity.

My own view is that MSF’s priorities are correct. Stopping the outbreak must always be job #1. One wants also to minimize risk to staff, but some risk is inevitable and must be accepted in order to end an Ebola outbreak. Curing patients is every doctor’s objective, but if a choice must be made stopping the epidemic is more important. Similarly, if staff start becoming infected at excessive rates we would lose the ability to either stop the outbreak or cure patients.

Saying that these priorities are correct does not, however, answer the question of how much can and should be done to cure patients.

My understanding, for example, is that MSF typically does no blood work apart from an initial test to confirm the diagnosis and final tests to confirm a cure. Often there would be no lab available to do additional testing anyway; it’s difficult and risky for a staff member wearing goggles and three layers of gloves to take a blood sample; puncturing the skin of an Ebola patient can lead to infection and/or uncontrolled bleeding; getting a blood sample takes precious time away from other patients; blood tests would cost money that might be better spent elsewhere; etc. etc. When regular blood tests are available, as in western hospitals, care can be customized to the patient’s individual needs. Infections can be identified and halted; imbalances in electrolytes identified and corrected, etc.

I presume that MSF would agree that a higher standard of care would be desirable, wherever it is feasible. The real question in each situation is where do you strike the balance between an aspiration for the best standard of care and the need to quickly isolate patients to stop the outbreak, as well as constraints of money and infrastructure. It may be that the MSF approach should be implemented quickly as soon as an outbreak is identified, then upgraded as time and resources permit.

Dr. Farmer’s push for a higher standard of care is directly opposed to a recent WHO proposal for “clinics” that would isolate patients but offer little or no medical care. [AP 10/2/14] This is a desperate response to the situation in Monrovia several weeks back where patients were being cared for at home — often infecting many household members — because there were no beds available. Since there now appear to be open beds it may be hoped that we don’t have to do in this inhumane direction, which explicitly sacrifices patient care to the overriding goal of stopping the epidemic.  [Economist 11/1/14]

Antibody Treatments

A handful of U.S. and African patients received the few available doses of ZMAPP, an artificial antibody treatment that has been successfully tested in monkeys. The U.S. patients survived and several of the African patients died, but the numbers are too small to reach any conclusions about its effectiveness. Similarly, several U.S. patients received antibodies in serum taken from survivors. The fact that they survived is encouraging, but again the numbers are too small at this point to support conclusions.