The Case for Social Distancing: Lessons from Cystic Fibrosis

April 7, 2020

Author Dr. Peter Gilligan on the left with infectious disease physician and epidemiologist Peter Leone on right at the Carrboro Farmer’s Market, March 14, 2020.
Source: Debbi Roos

I think a lot of people see this picture demonstrating the recommended 6 feet for social distancing and say "this is a lot of nonsense." As someone who has run clinical laboratories for the University of North Carolina Hospitals and, to a lesser degree, been involved the national response to the anthrax attack in 2001, Sudden Acute Respiratory Syndrome (SARS) in 2003 and influenza H1N1 2009, I have given considerable thought to the nation-wide move to social distancing. I am an enthusiastic proponent. I have seen it work against a microbe that is untreatable with antimicrobials and for which there is no vaccine, saving untold lives. Here is that story.

On a summer day in the early 1980s, I was on rounds with Dr. Sarah Long, the Chief of Infectious Diseases at St. Christopher’s Hospital for Children. I was the “new,” but really the “novice,” Clinical Microbiology Lab Director there. I did know that I knew very little about how to be a clinical microbiologist who could be helpful to doctors like Dr. Long, so I tagged along her Wednesday afternoon teaching rounds to see what I could learn so I could be “of use” to her, her colleagues and epecially her patients and their families. The patient I remember best from the rounds was a young man with cystic fibrosis (CF) who had graduated from high school just a few days before. Even to my unsophisticated eye, he was quite sick. Little did I know that he was about to change the direction of my life, and have a significant impact on the lives of many people with CF, just as he was quite sadly losing his own.

At the time of his admission, this young man was “old” for a person with CF, but prior to this admission, was in remarkably good health (a runner on the cross country team, something quite unusual at that time among people with CF). I went back to the laboratory after rounds and got his respiratory tract culture out to look at. He was growing a strain of mucoid Pseudomonas aeruginosa, the standard “bad actor” in CF lung disease, which causes as many as 80% of the chronic infections that eventually kill these folks. But as I looked more closely, I saw a second organism, Pseudomonas cepacia (now Burkholderia cepacia complex). Unlike the P. aeruginosa isolate, the other organism was resistant to all antimicrobials we were treating this patient with and, as we would subsequently learn, once present, this organism is rarely cleared from the CF lung.

When the young man died 2 weeks later, we did an autopsy and learned that although his P. aeruginosa was gone, the B. cepacia remained in his lungs. The CF docs at St. Christopher’s were very good at receiving permission for autopsies, and the generosity of CF families allowed us to gather important clues for understanding this disease process. My review of the autopsy data showed that 55% of CF patients had P. aeruginosa, something that was anticipated. Much more surprisingly, 42% on autopsy had B. cepacia, including 11% who had both. When I showed Dr. Dan Schidlow, the Chief of the Cystic Fibrosis service at St. Christopher’s, these data, he insisted we call the Center for Disease Control and Prevention (CDC) right away. The CDC sent two Epidemic Intelligience Service (EIS) officers, Ofelia Tablan and Terry Chorba, to help us understand what was happening in this population. From our collaboration, 3 important observations quickly emerged:
  1. B. cepacia was found in 18% of people with CF but in <0.5% of children without CF.
  2. This organism only caused serious disease in people with CF.
  3. The mortality in B. cepacia-infected individuals with CF after 90 days was 20%, whereas death for people with CF infected with P. aeruginosa generally occurred years to decades after initial infection. Two additional studies at large CF centers, in Cleveland and in Toronto, showed essentially the same information.
Where did this organism come from? How could we stop it from infecting and killing people? Because it is highly resistant to antimicrobials, B. cepacia-infected patients responded poorly (if at all) to antimicrobial treatment, and there is no vaccine. We also had no idea where people were getting it and how it was spread. We knew from environmental microbiology studies that it was a soil microorganism, but was that really how people were becoming infected?

John Govan and colleagues in 1993 determined that social contact among people with CF in a weekly exercise class, during attendance at a camp for CF children and at a holiday party all resulted in the acquistion of B. cepacia, with the deaths of several of the individuals. Evidence pointed to droplet spread of the organism as its major mode of transmission. Subsequent taxonomic studies showed what we intially called B. cepacia was actually a group of 20 closely-related species referred to as Burkholderia cepacia complex. One species, B. cenocepacia, which had spread throughout North America and Europe, was particularly deadly.

In 2003, based on a growing body of evidence, the Cystic Fibrosis Foundation published infection control guidelines right out of the same public health playbook that are now being applied to all of us. Essentially, those who are potentially infected must be isolated. Those who are at risk must not come in contact with those who are infected. Finally, social distancing and assidious personal hygiene are essential.

Early steps to control the spead of B. cepacia complex included closing all summer camps for children with CF, excluding more than 1 person with CF from all CF Foundation-sponsored indoor events, requiring social distancing of all attendees with CF at outdoor events and requiring respiratory isolation of all CF patients when admitted to the hosptial. All these steps meant young people who were used to spending time with their friends with CF were now socially isolated. For people with CF, their entire lives changed. They were not just required to practice social distancing, but effectively were isolated from an important peer group forever. Social distancing comes with significant individual costs, but also significant benefits for people with CF. Not surprisingly, adolescents with CF have found it particularly difficult to comply with these strictures. Despite the individual costs, the initial 2003 guidelines with many subsequent modifications remain the standard of care in the cystic fibrosis community.

How well has this policy worked? Simply put, very well. The prevalence of B. cepacia complex infection in the U.S. during 2017 among people with CF was 2.4%; it was 18% when we first studied it in the early 1980s. It is now likely that most aquistion of this organism is from the natural environment. Person-to-person spread has been limited. Life expectancies in people with CF have been buoyed by these difficult life strictures and an amazing array of new therapies.

The lesson from B. cepacia infections in people with CF, which are essentially untreatable and for which there are no vaccines, is clear. We can lessen the impact of an droplet spread infection causing high mortality by social distancing of the well and quarantine of the sick. It will be a significant inconvenience for all of us and threaten the livelihood of many. But as COVID-19 rages, do we really have a choice?

Author: Peter Gilligan, Ph.D., D(ABMM), F(AAM)

Peter Gilligan, Ph.D., D(ABMM), F(AAM)
Peter Gilligan is the former Director of the Clinical Microbiology-Immunology Laboratories of the University of North Carolina Hospitals.