Ebola transmission

I did some reading on this topic a week ago, and this has been sitting in my drafts for about a week.

In the last post I noted that NEJM recently stated

Health care professionals treating patients with this illness have learned that transmission arises from contact with bodily fluids of a person who is symptomatic — that is, has a fever, vomiting, diarrhea, and malaise. We have very strong reason to believe that transmission occurs when the viral load in bodily fluids is high, on the order of millions of virions per microliter.

The question of whether patients are contagious before they become symptomatic has come up in debates about whether quarantine is appropriate or hysteria. The judge’s decision in the case of Mayhew v. Hickox, where a returning MSF nurse contested Maine’s State Dept of Health and Human Services quarantine request repeats this. Citing an expert from the states equivalent of the CDC, the judge wrote:

Individuals infected with Ebola Virus Disease who are not showing symptoms are not yet infectious.

But others are not as sure:

Moreover, said some public health specialists, there is no proof that a person infected — but who lacks symptoms — could not spread the virus to others.

“It’s really unclear,” said Michael Osterholm, a public health scientist at the University of Minnesota who recently served on the U.S. government’s National Science Advisory Board for Biosecurity. “None of us know.”

[Dr. Philip K] Russell, who oversaw the Army’s research on Ebola, said he found the epidemiological data unconvincing

What is the actual data? Not being an epidemiologist nor a virologist, I’m not already familiar with the literature, and I am likely to miss things and not fully understand the field-specific issues and language. But I think I can at least get a superficial sense of what’s out there, and what questions I would want to ask a real expert. Bottom line: the expert opinion that only the symptomatic are significantly contagious looks pretty good to me.

The first thing I noticed was that the literature on transmission of Ebola includes lots of computer modeling and that like most other fields, the citations for facts that are regarded as well established are often to reviews that cite other reviews. In some cases papers cite things like the CDC website, where the information lacks references. But this 1999 review seemed like a pretty good introduction and starting point. Authors CJ Peters and JW Peters from the CDC summarize the history of Ebola outbreaks, and point out the difficulty of reconstructing what happened in many of the early cases. Baron, McCormick and Zubeir looked at the spread of Ebola in a 1979 outbreak in the southern Sudan.

Every case,except that of the index patient,could be traced to a human source of infection…
Details of exposure to infection were not available for 2 secondary cases; the other 27 were associated with physical contact. Of these, 24 had provided nursing care to other patients in the family; for the remaining 3 patients (including the 2 children) the history indicated that the physical contact had been less intimate.

More importantly, the large numbers of family members who did not get Ebola suggested that the virus is not easily transmitted without direct contact with bodily fluids. Antibodies in asymptomatic family members (who had contact) suggested infactions that never turned into symptomatic cases. There were no cases where these were the source of another infection. But the numbers were relatively small.

In January of 1995, a charcoal worker who probably got Ebola from a natural reservoir was admitted to the Kikwit General Hospital. Retrospective analysis showed that he infected his family in the area of Kikwit, and some of the secondary and tertiary patients went to the Kikwit II Maternity Hospital over the following months. The official index patient of the outbreak was a 36 year old male who worked in the Kikwit II Maternity Hospital as a lab tech. The lab tech presented fever and intestinal symptoms that led to surgery for a suspected perforated bowel.

He underwent laparotomy at Kikwit General Hospital for a suspected perforated bowel after protracted fever. Postoperative abdominal distention increased, and an abdominal puncture revealed bloody peritoneal fluid. The patient underwent a new laparotomy, which showed massive intraabdominal hemorrhage. Three days later, on 14 April 1995, the patient died.

By that time, medical personnel who had cared for the index patient were getting sick. Only then was a viral hemorrhagic fever suspected. CDC confirmed that it was Ebola on May 10 after getting samples from Zaire the day before. Even before the confirmation, the government had declared an epidemic. By the end of the Kikwit outbreak, 316 people were known to have gotten Ebola, and 285 deaths were attributed to Ebola. This provided another opportunity to look at who gets Ebola and who doesn’t during an outbreak.

Dowell et al looked at risk factors for transmission of Ebola within families in the Kikwit outbreak. The results are overall in agreement with what was seen in Sudan.

The exposure that was most strongly predictive of risk for secondary transmission was direct physical contact with an ill family member, either at home in the early phase of illness or during the hospitalization. Of 95 family members who had such contact, 28 became infected, whereas none of 78 family members who did not touch an infected person during the period of clinical illness were infected (RR, undefined; P < .001). Nevertheless, the 78 family members who did not report direct physical contact with an ill person during the clinical phase of illness participated in a variety of activities that would have exposed them to fomite or airborne routes of spread. During the incubation period, all 78 shared meals with their ill family member, 26 reported direct physical contact, 15 shared their bedroom, and 6 shared their bed. In the early phase of illness, 62 slept in the same house and 42 shared meals. During the late phase of illness, 24 visited the hospital and 18 spoke with their ill family member.

Of the 316 patients, the majority had a known source of exposure, but 55 were initially unexplained. Roels et al went back and reexamined the available epidemiological information for 44 of these 55 (8 couldn’t be found and 3 refused to participate).

The probable source of exposure was identified for 32 (73%) of the 44 patients. Seventeen had visited an ill friend or relative with symptoms suggestive of EHF, 9 had been admitted to a health center in the 3 weeks preceding onset of EHF symptoms, and 6 had both risk factors. Of the 23 who had visited an ill friend or relative with symptoms suggestive of EHF, 4 (17%) resided in the same household as the ill patient and were their caregivers, 14 reported touching the ill patient, and 5 visited without touching the patient.

This leaves 12 people unaccounted for, and these 12 are sometimes cited as a problem for the conventional wisdom.

we identified an exposure source for 32 of 44 patients for whom no source was originally reported. Of the 12 patients who did not have an identified exposure source, no sociologic, occupational, or dietary risk factors for illness were found. Direct person-to-person contact was the likely mode of transmission for most EHF cases during this outbreak. However, our findings suggest that other EHF transmission modes cannot be excluded and may account for infection in those individuals for whom no previously recognized mode of transmission could be documented.

Although the alternative transmission cannot be formally eliminated, it is important to note that the 12 should also not be taken as proof of alternative transmission. In fact, none of them were actually confirmed as even having Ebola based on culturing the virus (See Table 3). There are also questions of the ability of the researchers to really reconstruct the contacts for each of these 12 people.

In the recent outbreak there are cases of health care workers who have contracted Ebola despite precautions. This could mean that there is a route of transmission that bypasses the protective protocols… or the simpler explanation is that errors in following the protocols led to transmission by the accepted route of direct contact with virus-laden bodily fluids. The Spanish nurse who has now recovered says she doesn’t know how she got it, but earlier reports talk about contact with gloves as she removed protective gear. For at least one of the nurses from Dallas, there are reports that she contacted Thomas Duncan in the ER without protective gear, before it was recognized that he was an Ebola patient.