Siddhartha Mukherjee

Detecting Ebola at an earlier stage

A man dressed in protective clothing treats the sidewalk in front of an apartment where a second person diagnosed with the Ebola virus resides on October 12, 2014 in Dallas, Texas. -- PHOTO: AFP
A man dressed in protective clothing treats the sidewalk in front of an apartment where a second person diagnosed with the Ebola virus resides on October 12, 2014 in Dallas, Texas. -- PHOTO: AFP

One feature of the tragic case of Mr Thomas Eric Duncan, the first traveller known to have carried the Ebola virus into the United States, rankles me as a physician: Even if every system in place to identify suspected carriers had been working perfectly, he might have still set off a mini-epidemic in Dallas.

Mr Duncan, recall, was screened before his flight and found to have a normal temperature. Asked specifically about exposures, he denied any contact with the ill. On Sept 25, when he first presented himself to the emergency room with a fever, he was discharged. He returned three days later with fulminant infection. But the fact remains that even if Mr Duncan had been identified and isolated on the first visit, it might have been too late. He had probably been exuding the virus for days.

The news that a nurse who helped treat Mr Duncan has now tested positive for the disease, evidently because of a breach of safety protocols, adds to the picture of disorder.

In the wake of the Duncan case, three strategies to contain the entry and spread of Ebola in the US have been proposed.

The first suggests drastic restrictions on travel from Ebola-affected nations. The second involves screening travellers from Ebola-affected areas with a thermometer, which the federal government is beginning to do at selected airports. The third proposes the isolation of all suspected symptomatic patients and monitoring or quarantining everyone who came into contact with them.

Yet, all these strategies have crucial flaws. In the absence of any established antiviral treatment, we may need to rethink the concept of quarantine itself.

An indiscriminate ban on travel would make it impossible for aid workers to reach the most widely affected areas, obviously deepening the medical and humanitarian crisis. It would also encourage subversion: Travellers might pass through other countries, confounding efforts to track their origin.

Screening travellers from affected areas using questionnaires and temperature may prove effective, but here, too, there are profound weaknesses. Low-grade fevers can easily be concealed with antipyretics like Tylenol.

More importantly, by the time an Ebola carrier has a fever, he is already in an infectious phase and may have exposed many others to the virus.

Isolating symptomatic patients is certainly effective, but it will not work as a proactive strategy of containment. By that point, a carrier may have already infected dozens of people. Even when surveillance is well deployed, the collateral costs associated with it are forbidding.

There is a fourth strategy, although it will need to be evaluated and deployed carefully. Since the 1990s, novel methods have allowed doctors to detect viruses in the pre-symptomatic phase of an infection, often with remarkable sensitivity and precision.

One of these involves the polymerase chain reaction, or PCR, a chemical reaction that amplifies pieces of a virus' genes floating in blood by more than a millionfold, which is what makes early, pre-symptomatic infections identifiable. The technique is not particularly cumbersome: As an oncologist working with blood cancers, I have been using variants of it to detect subclinical infections in patients for nearly a decade.

A 2000 study in The Lancet illustrates the power of this approach. Twenty-four "asymptomatic" individuals exposed to Ebola were tested using PCR. Eleven of the exposed patients eventually developed the infection. Seven of the 11 tested positive for the PCR assay; none of the other 13 did.

In 2004, virologists at the Centres for Disease Control and Prevention further refined this method to increase its sensitivity. The test now requires only a teaspoon of blood. The sample is transported on ice to a centralised lab. Results are back in a few hours.

Technologies like this allow us to imagine a new form of quarantine. Rather than relying on primitive instruments, indiscriminate profiling or questionnaires, we should consider running a pilot programme to test asymptomatic travellers using sensitive PCR-based techniques.

Obviously, such technologies are expensive, but the cost is not prohibitive. A typical PCR reaction, including labour, costs between US$60 (S$80) and US$200 (we have already spent 100 times more disposing of the contaminated sheets from the apartment Mr Duncan stayed in). Since the test takes about a third of the time of a trans-Atlantic flight, the flight would become the quarantine.

Huge logistical questions would need to be resolved. Where would such a screening test be administered - before departure from West Africa or upon landing in the United States? Could we imagine a walking quarantine in which travellers were granted provisional entry, but recalled if they tested positive? What infection precautions would need to be in place for such testing? What forms of consent would be required? Who would bear the costs? Who exactly would be tested?

Despite these questions, we should develop a pilot programme, perhaps targeting the worst-hit regions of the epidemic.

One major issue with this kind of rapid-testing quarantine is the phenomenon of false positives. But PCR-based testing for Ebola has a low false-positive rate (three per 1,000), and its accuracy could be further improved by focusing on patients who come from particular geographic regions or by using more refined questionnaires.

The second problem is false negatives: missing actual carriers of the infection. And yet, at four false negatives per 1,000, the detection rate might be sufficient to keep Ebola from becoming epidemic in the US. Even the presence of such a testing and tracking system would act as a deterrent to those who wish to evade detection.

A rapid-testing quarantine would be expensive, but a pilot programme might teach us much more about how to move forward. It certainly does not solve the civil liberties questions of quarantining, but it makes them vastly more palatable.

Ebola is an ingenious virus. To fight it, we need to be just as ingenious.