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By Gary Evans, Executive Editor
The Ebola epidemic in Africa is rapidly overwhelming containment efforts, increasing the threat of spread to other countries and continents while giving the virus ample time to mutate as it burns through the human population in a jungled epicenter that borders three nations.
"The border of the three areas — where Guinea, Sierra Leone and Liberia meet — is a dense forested region with roughly about one million people in it," said Tom Frieden, MD, director of the Centers for Disease Control and Prevention. "That has been the epicenter, if you will, the crucible of this outbreak. That is where most of the cases have been, where it’s continued to smolder and burn throughout all of these outbreaks, and where we believe it likely started."
In an urgent addition to the Ebola situation, federal public health officials recently issued a checklist for U.S. hospitals to prepare for incoming cases from the expanding outbreak in Africa. (See related story, p. 100)
Having just returned from the region, Frieden said the number of cases is increasing rapidly and it will now take a global response to stop the worst Ebola outbreak on record. "Everything I’ve seen suggests over the next few weeks it’s likely to get worse," he said at a Sept. 2, 2014 press conference at the CDC. "We’re likely to see significant increases in cases."
Indeed, an infectious disease strategic planner for the World Health Organization (WHO) recently told the BBC News in London that the current rate of some 500 new Ebola cases a week is increasing exponentially.1
"I’ve just projected about five weeks into the future and if current trends persist we would be seeing not hundreds of cases per week, but thousands of cases per week — that is terribly disturbing," said Christopher Dye, FRS, FMedSci. "The situation is bad and we have to prepare for it getting worse."
As of August 31 2014, 3,685 (probable, confirmed and suspected) Ebola cases and 1,841 deaths had been reported by the Ministries of Health of Guinea, Liberia and Sierra Leone, according to the WHO. In Nigeria, there have been 21 cases and 7 deaths while in Senegal, one case has been confirmed and there have been no Ebola deaths or further suspected cases. The involvement of more countries is particularly concerning, as international air travel routes and connections could eventually disperse asymptomatic passengers traveling during an incubation period that can last up to three weeks.
In what appears to be an incredible case of bad luck — given the heretofore relatively rare occurrence of Ebola — an unrelated outbreak has also erupted in the Democratic Republic of the Congo (DRC), where runs the eponymous Ebola River. A total of 24 suspected cases of Ebola, including 13 deaths, have been identified and linked to that outbreak, which is occurring in central Africa were Ebola was first detected in 1976. The Congo outbreak has been traced to a single person who became infected after preparing bush meat for consumption. The outbreak in West Africa is thought to have begun when a toddler became infected by handling a fruit bat, one of the known wild reservoirs for the virus. The Congo virus is also of the Zaire species, but its lineage is more closely related to a virus from the 1995 Ebola outbreak in Kikwit, DRC, the WHO reported.
"Results from virus characterization, together with findings from the epidemiological investigation, are definitive: the outbreak in DRC is a distinct and independent event, with no relationship to the outbreak in West Africa," the WHO reported.
For planning purposes, the World Health Organization is currently estimating that the outbreak in West Africa may peak at 20,000 cases, but some scientists think it could far exceed that. An elaborate mathematical model developed by Alessandro Vespignani, PhD, of Northeastern University in Boston predicts the outbreak will reach 10,000 cases as early as September 24, 2014 if control efforts are not dramatically improved.2 His one-line assessment of the situation was starkly non-scientific in an email interview: "The numbers are really scary."1 Vespignani and colleagues estimated that the spreading Zaire strain of Ebola in West Africa has a reproductive ratio of 1.5 to 2.0. Typically any etiologic agent reaching a reproductive ratio of 1 and above will continue to spread and cause new infections.
"The numerical simulation results show a steep increase of cases in the West Africa region, unless the transmissibility of [Ebola] is successfully mitigated," the authors warn. "The probability of case exportation is extremely modest (upper bound less than 5%) for non-African countries, with the exception of the United Kingdom, Belgium, France and the United States. We show by a modeling effort informed by data available on the 2014 [Ebola] outbreak that the risk of international spread of the Ebola virus is still moderate for most countries. The current analysis however shows that if the outbreak is not contained, the probability of international spread is going to increase consistently, especially if other countries are affected and are not able to contain the epidemic."
There is widespread consensus among investigators that the known count of Ebola cases and deaths underestimates the real toll of the epidemic — possibly by two- or three-fold — as cases and contacts elude surveillance efforts.
"Staff at the outbreak sites see evidence that the numbers of reported cases and deaths vastly underestimate the magnitude of the outbreak," the WHO stated.
The incubation period is 8 to 10 days on average, with 21 days being the outer limit. Thus those infected could be geographically dispersed to just about anywhere before the onset of the symptoms begin and they become capable of transmission to their contacts.
Given these troubling signs, Frieden said it "is certainly possible we will see cases elsewhere. That’s why we are alerting clinicians throughout the U.S. to think of Ebola, [identify] people who have been traveling to countries that have been affected, and rapidly test for it. We have helped laboratories around the U.S. become able to test for Ebola safely and accurately. That’s in place now so that testing can be done quickly."
The CDC continues to emphasize that U.S. hospitals can handle cases with a combination of contact and droplet patient isolation precautions, though a respirator at least equivalent to an N95 should be worn if a procedure is likely to produce aerosols. The CDC recommends keeping the patient’s door closed and posting someone outside the room to sign people in and out.
"The current CDC recommendations make practical sense," said Terry Rebmann, PhD, RN, CIC, director of the Institute for Biosecurity at St. Louis (MO) University. "They are very reasonable and if they are enforced consistently they should be able to contain the disease. We are less concerned about in the United States as long as practitioners and clinicians are really very stringent about infection prevention."
In addition, the CDC recently issued recommendations for environmental cleaning of Ebola patient rooms, though conceding there is paucity of data to base guidance on. (See related story, p. 103.) "We don’t think Ebola would spread widely within the U.S — routine health care infection control would probably prevent most transmission," Frieden said. "We have had five cases of other bleeding viruses in the U.S. over the past decade. Four of a virus called Lassa, one of Marburg — very much like Ebola. Even though they were not identified in the hospital before they were diagnosed — even though people did not take special precautions — there was not a single secondary spread from that. That doesn’t mean there couldn’t be a family member or health care worker who doesn’t think’ Ebola [and becomes infected]."
In a sense, the recent introduction of the first MERS cases in the United States can serve as a trial by fire, as the critical component of discerning travel history of symptomatic patients still serves as the first triage point. MERS can be confused with community acquired pneumonia or other severe respiratory diseases, but a symptomatic Ebola patient should be somewhat easier to identify, Rebmann said.
"The recommendations are similar in that both are severe communicable diseases with high mortality," she said. "With Ebola the symptoms are relatively severe, which should make identification and surveillance a little easier. Clinicians should make sure that if someone does present with an unusual illness they should be asking about travel history and considering the incubation period for Ebola."
Still, there’s something of a mixed message to this outbreak, as infected American caregivers returning to this country are being admitted to specially designed, failsafe biocontainment units like those at Emory Healthcare in Atlanta and the University of Nebraska in Omaha. (See related story, p. 102.) Compounding this confusion, health care workers in the outbreak zone in Africa are shown wearing extensive barrier precautions that go beyond what the CDC is recommending for U.S. facilities.
"SHEA is concerned about the mixed messages that our health care workers, patients and others receive when they see that health care workers in outbreak zones are dressed in moon suits and using respirators consistent with airborne spread," said Daniel Diekema, MD, president of the Society for Healthcare Epidemiology of America (SHEA). "The message that we are trying to reinforce is that there is a vast difference between reducing risk in an outbreak setting where there are limited resources and limited access to things like potable water or water for hand hygiene. Health care workers may spend many hours in large multipatient wards providing continuous care for many very sick patients with absolutely no idea when or how their next exposure may occur. This is very different from the controlled setting of an acute care hospital in the U.S."
Moreover, erring on the side of excessive precautions could actually increase the risk to workers if they have not been adequately trained to don and remove the equipment, Diekema added.
"We are working with the CDC to try to get this message across because there are some risks of hospitals overreacting — not just in resource utilization but some practical issues as well," he told Hospital Infection Control & Prevention. "For example, if a hospital felt they needed to introduce a brand new, unfamiliar form of personal protective equipment (PPE) without proper training it could paradoxically increase the risk of the HCW contaminating themselves — [unless they are] well trained in how to remove that personnel protective equipment."
While in Africa, Frieden donned the full regalia of PPE to enter an Ebola care clinic run by the Doctors without Borders volunteer group.
"I felt completely safe," he said. "You’re basically swaddled in protective gear. If you’re not risking a needle stick, the risk is essentially nil. The challenge is things like removing [the PPE] if that equipment is soiled and doing that very, very carefully. Doctors without Borders is extraordinarily careful in doing that. As I came out of the treatment unit, a local person trained by [them], was basically screaming at me, Hold your hand this way, do this, move this way,’ and spraying me down with bleach at every step. The biggest risk to health care workers has not been in the Ebola treatment units. It’s been in the general health care system because Ebola in these countries doesn’t look very different from a disease like malaria, typhoid or gastroenteritis. When it starts, it has very similar symptoms."
CDC epidemiologists on the scene are teaching their African colleagues how to set up triage points, putting possible Ebola patients in one group and other patients in a separate area.
"For those who might have Ebola, assume that they do until proven otherwise," Frieden said. "One of the real challenges in these countries — particularly Liberia and Sierra Leone — is getting the health care system up and running again. Ebola is not just harming people by [infections], it’s essentially shutting [down] much of the health care system. People are afraid to go — health care workers are afraid to go. That’s exacerbating the situation. One of the things we are doing is helping to establish a core level of infection control at every health care facility throughout the country so health care workers are better protected."
Compounding the problem are unsafe burial rituals where the bodies of those who have just died of Ebola are handled and washed. The virus can still spread from a corpse but changing cultural morays of honoring the dead has been difficult. The harsh conditions and lack of public health infrastructure make the laborious work of tracking down contacts of cases and monitoring them for symptoms for a three-week incubation period all the more difficult. Disease fighters may face both ignorance and distrust, as they are seen by some as spreading the virus rather than trying to eradicate it. For example, a recent spike of cases in Guinea was met by resistance to prevention measures in one village.
"This is a community which does not have access to radio, which has been isolated, and which has a lot of misconceptions," Frieden said. "For example, when people were going in with sprays of bleach to sterilize after people had died, the rumor went around that [the spray] was spreading Ebola."
Though the global effort must rapidly increase to meet the threat, Frieden cited the establishment of laboratories and other assistance by teams from the European Union, China, South Africa and Canada. Still, much more assistance is needed if the outbreak is to be contained, he warned.
"The number of cases is increasing so quickly that for every day’s delay, it becomes that much harder to stop it," Frieden said. "There are three key things that we need. The first is more resources. This is going to take a lot to confront. The second are technical experts in health care and management to help in country. And the third is a global coordinated unified approach. This is not just a problem for West Africa, it’s not just a problem for Africa, it’s a problem for the world and the world needs to respond."
Given that this is the longest lasting Ebola outbreak in history, concern is mounting that the virus could mutate and become more transmissible as it continues to infect people. "That risk may be very low, but it’s probably not zero," Frieden said. "The longer it spreads, the higher the risk."
WHO Director Margaret Chan, MD, warned in a speech to the affected countries that "constant mutation and adaptation are the survival mechanisms of viruses and other microbes. We must not give this virus opportunities to deliver more surprises." Even President Obama weighed in on the risk of mutation, saying in a recent interview, "We have to make this a national security priority. We have to mobilize the international community, get resources in there . If we don’t make that effort now, and this spreads not just through Africa but other parts of the world, there’s the prospect then that the virus mutates. It becomes more easily transmittable. And then it could be a serious danger to the United States."
The virus has already made numerous subtle mutations, though none that would clearly enhance transmission, increase virulence or impair diagnostic detection. Researchers recently generated 99 viral genome sequences from 78 confirmed Ebola patients.3 "Phylogenetic comparison to all 20 genomes from earlier outbreaks suggests the 2014 West African virus likely spread from Middle Africa within the last decade," they reported. "Genetic similarity across the sequenced 2014 samples suggests a single transmission from the natural reservoir, followed by human-to-human transmission during the outbreak. "
Thus, continued exposures between humans and viral reservoir animals (i.e., fruit bats) does not appear to be a factor in this outbreak. The genomic data also showed a strong epidemiologic link between acquiring the virus and attending a funeral.
The genomic analysis revealed some 50 "mutational events," though "determining whether individual mutations are deleterious, or even adaptive, would require [more] analysis," the authors report. "However, the rate of mutations suggests that continued progression of this epidemic could afford an opportunity for viral adaptation, underscoring the need for rapid containment."
In a grim postscript to the paper that underscores just how dangerous it is to try and stop an Ebola epidemic, the authors conclude by observing, "Tragically, five co-authors, who contributed greatly to public health and research efforts in Sierra Leone, contracted [Ebola] in the course of their work and lost their battle with the disease before this manuscript could be published. We wish to honor their memory."