Musings To Watch Outbreaks By

Credit - HK Gov

#14,622

It's now been just over 6 days since we began to hear reports of an unidentified pneumonia in Wuhan City, China; one that had hospitalized (at 1st report) 27 people.  As of yesterday, that number had more than doubled, to  59 (7 in critical condition).

The cause, and full extent, of this outbreak remains unknown, and unfortunately we are lacking some very basic epidemiological patient data (age, gender, onset dates, hospitalization dates, relationship to other cases, comorbidities,  etc.) that might shed valuable light on this event. 

Yesterday the WHO released their first statement on the outbreak, which adds very little to what we already had been told. They are in consultation with China, stand ready to help, and have requested `. . . further information on the laboratory tests performed and the differential diagnoses considered.'

But for now, they state: `There is limited information to determine the overall risk of this reported cluster of pneumonia of unknown etiology.' 

Reportedly, influenza (both seasonal & avian), along with adenovirus infection, have been ruled out by laboratory testing. SARS and MERS-CoV also appear to have been eliminated, although other coronaviruses might still be in play. Recent reports are a bit more vague over how many of the hospitalized cases are linked to the Wuhan seafood market - going from early reports of `nearly all' to only `some'.

Beyond that, we are basically in outbreak information limbo, and must take our cues mostly from the public health responses of Mainland China's nearest neighbors; Hong Kong, Macao, and Taiwan (see Hong Kong Activates New Infectious Disease Preparedness & Contingency Plan (`Serious' Level).

Some of their reactions - like isolating and testing symptomatic travelers from Wuhan City - are prudent (and reassuring to the public) - and may yield some clues - but they are also subject to misinterpretation by the press and social media pundits.

This is cold & flu season, and some percentage of travelers from Wuhan City (or any place else, for that matter) can be expected to exhibit fever and/or respiratory symptoms.

While it is possible that some of these travelers might be carrying whatever is causing the Wuhan pneumonia outbreak, most will almost certainly be found to be sickened with influenza, rhinovirus, or some other common respiratory virus. 

Headlines - like yesterday's  8 new patients with unknown viral pneumonia in Hong Kong -  make it sound as if the Wuhan pneumonia has been detected outside of Mainland China, when in fact, none of these Hong Kong patients have (as yet) been diagnosed as having the same condition.

Most respiratory virus infections - at least in the early stages - look pretty much the same; fever, malaise, respiratory symptoms, etc.  This is why we use the term ILI (Influenza-Like-Illness) so often, as influenza, RSV, rhinovirus, adenovirus, coronavirus, and others infections are virtually indistinguishable without laboratory testing.

While we have specific tests for these common viral infections (tests that can even detect new subtypes of influenza A) -  isolating and identifying a new virus - well, that can take time.  Weeks, or sometimes even months. 

As we've discussed previously, the cause of more than half of all community acquired pneumonia infections are never identified, even here in the United States.  The results from 2015's CDC EPIC CA-Pneumonia Study, found:

After five years and nearly 2,500 eligible patients (median age 57), the latest published results (in the NEJM) revealed that in the majority (62%) of cases no definitive pathogenic agent was identified – and among those that were – viral infections out-numbered bacterial infections by roughly 2:1.

Specifically, they found:

• one or more viruses in 530 (23%) cases
• bacteria in 247 (11%) cases
• bacterial and viral pathogens in 59 (3%) cases
• and a fungal or mycobacterial pathogen in 17 (1%) of cases

All of which means that getting a definitive diagnosis out of China may take a while. And even assuming a new virus is identified in some of these pneumonia cases, proving causality isn't necessarily easy.

While several enteroviruses (EV-D68, EV-71, etc.)  have been implicated, more than 5 years after the first big outbreak of AFM (Acute Flaccid Myelitis), the CDC is still investigating the likely cause. 

Although I remain hopeful that we'll learn the etiology of this pneumonia outbreak in the days ahead, and that a diagnostic lab test will become available, the reality is it may take some time. And until that happens, diagnosis is going to be mainly one of exclusion; a viral pneumonia that tests negative for everything else.

In addition to discovering the cause of the Wuhan pneumonia cluster, determining it is spread (how, how much, and how fast) is very much at the top of our wish list.

Yesterday's WHO update stated that China has found `. . . no evidence of significant human-to-human transmission and no health care worker infections have been reported.'

While reassuring, the bar for determining H-2-H transmission of an unknown virus is purposely set pretty high. And since we only know about hospitalized cases - which may represent just a fraction of the total number of infections - we may not have all the information needed to make that call.

In epidemiology, a Line Listing is one the most basic methods used to collect, display, and analyze outbreak information. It is essentially a table that displays individual cases in rows, and their characteristics in columns. If you’ve ever prepared a spreadsheet, you know the format.

A simple example might look something like this:

Photo – CDC Excite Epidemiology in the Classroom

China is almost certainly doing this kind of old-fashioned shoe-leather epidemiology; the tracking down of contacts, the gathering of extensive histories, and the laborious compiling and analysis of epidemiological line lists. 

Hopefully they are sharing it, if not publically, at least with WHO and other public health entities.  

While we wait for better answers, it is worth remembering that these sorts of investigations often turn into more of a marathon than a sprint.  It took nearly a year for researchers to figure out that camels were a carriers of the MERS-CoV virus, and that exposure to them was a major source of human infection.

For now, we simply have too little information to guess where this outbreak investigation will lead, or how much (or little) of a threat this outbreak poses. Whatever the answers, we should expect to be surprised.

And if we should happen to get lucky, and this threat recedes, we should be prepared to deal with others like it in the decade ahead.  Nature never stops trying. 

Stay tuned.