Ebola: A slow-motion atomic bomb

By Devabhaktuni Srikrishna, Ranu S. Dhillon, November 25, 2014

We are in the midst of the worst Ebola outbreak in human history. After four decades of confining outbreaks of this disease to small areas, experts acknowledged in an October 9 New England Journal of Medicine article that “we were wrong” about the scope of the current situation. And the co-discoverer of Ebola, Peter Piot, told The Guardian on October 4 that until this year he thought that Ebola was never “much of a problem because the outbreaks were always brief and local.”

The present Ebola outbreak is like a slowly exploding atomic bomb in Africa: Each Ebola patient infects an average of 1.5 to 2.0 additional people. To shut down the Ebola epidemic in West Africa means getting that number—known as the “transmission rate” or reproductive number—to below 1.0. To give a sense of what those figures mean, at the present rate, the number of Ebola cases in West Africa doubles every two to three weeks.

And there are several complicating factors. For one thing, the Centers for Disease Control and Prevention (CDC) estimate that 60 percent of all Ebola patients remain undiagnosed in their communities. For another, there is some evidence that organizations such as ISIS are interested in acquiring biological weapons; Ebola is listed as a bioterrorism agent by the CDC, and this uncontrolled epidemic is giving terrorists a virtually unlimited supply of Ebola virus that they would otherwise have had to produce with much greater effort, risk, and expense. And if terrorists do manage to expose a large number of people in public locations, Ebola becomes that much harder to control, because each infected patient caused by such a terrorist attack would be likely be unknown or untraceable, along with all of his or her contacts.

Despite the fact that news about Ebola seems to be receding from the front pages of Western newspapers and from the home pages of American news sites, the fight against Ebola is not over. While case counts have been declining recently in Liberia and reports suggest the epidemic is stable (slowly increasing) in Guinea, it is by no means under control and can flare up unpredictably due to a variety of circumstances. The outbreak is reported to be worsening in neighboring countries such as Sierra Leone.

So we need to act sooner rather than later, reduce the transmission rate to below 1.0 in West Africa, and shut down the Ebola epidemic. But to reduce the window of opportunity for transmission requires early diagnosis followed by rapid isolation and treatment. And therein lies the rub.

Early diagnosis is key, but hard. Ebola is a stealth bug. Diagnosis without lab tests is challenging because Ebola presents itself with non-specific symptoms that can easily be mistaken for routine diseases such as malaria, typhoid, gastroenteritis, or the flu. Once symptoms appear, Ebola quickly transmits itself through routine contact and caregiving—via direct contact with victims’ bodily fluids including blood, diarrhea, vomit, and even sweat. So without precautions to prevent transmission, such as protective suits and disinfectants, there is a high likelihood of Ebola spreading to household family members, healthcare workers, ambulance drivers, and even those who merely ride in the same vehicle that was used to transport the patient—including Good Samaritans who helped to take the patient to a hospital. The disease has the potential to spread to just about any caregiver, including those dealing with the bodies of deceased Ebola victims.

Transmission would be much easier to prevent if the disease were not so stealthy. Imagine if a visible halo appeared around everyone infected with Ebola: People around the afflicted could be mindful to take all necessary precautions to protect themselves; cases could be identified more easily; and patients could be isolated and treated. Ebola transmission rates would plummet.

After they show symptoms, patients can be definitively diagnosed using tests that incorporate the Polymerase Chain Reaction (PCR)—a sort of genetic copying machine that amplifies the number of strands of identifiable DNA of an organism, thereby making it easier to spot the genetic markers that identify a given disease as surely as a thumbprint. These tests require special equipment and training; at present less than a few dozen labs in Liberia, Sierra Leone, and Guinea can do this kind of work, although more are in the pipeline.

To cope with the severe shortage of diagnostic capability, today’s Ebola treatment centers in West Africa need to separate patients into three wards based upon a physician’s clinical judgment of whether they have Ebola: low-probability, high-probability, and confirmed Ebola cases. The medical humanitarian organization Doctors Without Borders reports that it can take up to several days for PCR test results to come back, because the blood samples need to be shipped to distant, regional laboratories in the cities, far from the remote field stations in the countryside where many patients are often treated. Consequently, if PCR labs could be located and staffed next to Ebola Treatment Units in the field, that would help to alleviate the shortage. The United States is sending 10,000 PCR test kits to Liberia and Sierra Leone, but as Ebola survivor and doctor Kent Brantley observed in his US Senate testimony, “More kits are not effective unless we have the facilities and the staffing to use them.” Training in safe and effective Ebola testing procedures for community health workers will be required to bring the transmission rate below 1.0.

Rapid diagnostic tests: A better, faster way of diagnosing Ebola? Most calls for action focus on beds and health workers—both unquestionably needed. While vaccines and treatments for Ebola remain under development, rapid and accurate testing by community health workers in patients’ homes is needed now to reduce the window for transmission. As described in our recent article in The Lancet, bringing the transmission rate below 1.0 requires a comprehensive three-step system: immediate protection of people in the home as soon as someone shows symptoms; same-day diagnosis in the home itself; and immediate secure transport to a treatment center (or safe isolation and treatment at home).

PCR is considered the gold standard in test accuracy for Ebola, but it also requires drawing blood with a butterfly needle (a needle designed for easily accessing surface veins) and syringe into a vacutainer (a collection tube with a vacuum). This procedure introduces some risk of transmission to healthcare workers in the community, especially for unqualified blood drawers who need to poke around with a needle to find a vein—creating a hazard for themselves and others around them. Due to the severe shortage of trained health workers needed in a short time frame, there may also be a practical limit to how quickly PCR testing can be scaled up to allow for every village to have one while also maintaining safety standards for those involved.

An emerging technology to scale up testing in a safer and less cumbersome way may be just around the corner. Rapid diagnostic tests are under development from at least seven different companies, universities, and governments. The goal of such a test kit is to provide near-immediate results, in a matter of minutes or hours, using just a single drop of blood, and no trip to a distant lab. Rapid diagnostic test kits have been used for a variety of other infectious diseases including influenza, malaria, and dengue. In the case of Ebola, a rapid diagnostic test kit would only require a small drop of blood with a single-use, disposable, and user-friendly safety lancet—which is generally safer and less error-prone overall for the health worker and the patient than using a needle to draw a vial of blood for PCR. A bandage can be applied over the puncture that quickly seals. Ensuring safety requires training, but less than it takes to learn how to draw blood with a needle and syringe.

A company called Corgenix is testing and manufacturing one version of rapid diagnostic test technology that was developed by Robert Garry and the Viral Hemorrhagic Fever Consortium at Tulane University. While rigorous field trials and lab tests are still underway, early indications are that the kits have fewer than 10 percent false negatives and close to zero percent false positives. In addition, each individual test conducted with rapid diagnostic technology is relatively inexpensive, so retesting could be performed easily and affordably to confirm a negative test result. In the future, it may become possible for rapid diagnostic tests to use other bodily fluids such as saliva, sweat, or mucus, eliminating the need to draw any blood.

Ebola control also requires fast isolation. Even if 100 percent of Ebola patients are eventually isolated, if enough other people have been exposed to the virus in the meanwhile—during the critical period after exposure but before isolation and treatment—then the epidemic can still grow exponentially. So a key part of bringing Ebola under control lies in reducing the window of time that passes between the appearance of the first symptoms—when the patient first becomes contagious—and the patient’s placement in a treatment and isolation ward.

In agreement with a CDC modeling study, the United Nations Mission for Ebola Emergency Response recommends that 70 percent of Ebola patients in West Africa be isolated in order to bring the epidemic under control. However, this target does not include any reference to the required speed of isolation.

Using a standardized computer model for Ebola epidemics developed by Gerardo Chowell from the National Institutes of Health, we sought to answer this question, and estimate the minimum proportion of patients who need to be isolated (i.e., hospitalized) in order to prevent uncontrolled growth. We discovered that the percentage of patients that need to be isolated is not an absolute figure, but actually varies depending upon how quickly patients can be isolated. The more time that goes by before isolation, the more opportunities for an infected person’s blood, sweat, diarrhea, vomit to come into casual contact with new people, exposing the newcomers to the disease and possibly infecting them. Consequently, the more time that passes, the greater the percentage of patients that must be isolated to bring the epidemic under control.

As the time between the appearance of symptoms and the moment a patient is isolated varies from one to five days, between 60 percent and 90 percent of Ebola patients would need to be isolated. Beyond six days, even 100 percent isolation may be insufficient. If infected patients could be isolated within 1 day or less, the epidemic could be tamed with less than 60 percent of infected patients. Our simulations found that a target of two days or less would need to be achieved for an isolation target of 70 percent to control the epidemic. (By comparison, UK researchers Neil Ferguson and W. John Edmunds report that in their epidemic models, a target of three days would be required for an isolation target of 70 percent to control the epidemic).

Even with a 10 percent false negative rate, easy-to-use rapid diagnostic tests in the hands of trained community health workers (not just at hospitals and Ebola treatment centers) could scale up test coverage to a sufficient number of patients in the fight against the Ebola epidemic. Once tested positive at home, the patient’s caregivers could take precautions using home protective kits until the patient can be safely and securely transported to an Ebola Treatment Unit in order to reduce transmission.

Every day counts. The simple-minded Ebola virus is so far outsmarting many well-intentioned yet uncoordinated efforts to stop it. On September 16, President Obama announced a plan to allocate $763 million and 3,000 troops to help bring the epidemic under control in Liberia, constructing 17 treatment centers containing 1,700 beds at a cost of more than $500,000 per bed—and as many as 80-to-90 percent of those beds are now expected to go unfilled because the treatment centers aren’t in the places where patients need them most. What’s more, this plan does not include a strategy for early diagnosis.

Unless there is a way to identify the majority of Ebola cases that are currently undiagnosed and unreported, the plan will not succeed in curbing transmission. If there were a $100 rapid test for Ebola that could test everyone who has a fever in Liberia (perhaps 5 percent of a population of 10 million people, or 500,000 individuals), it could identify all the cases of Ebola for $50 million and possibly enable a more targeted approach that would put an end to this epidemic much more quickly.

Diagnostics can be just as important to epidemic control as treatment beds.


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