A curious paper on the 1918 flu pandemic appeared this month in CDC’s journal, Emerging Infectious Diseases. It seemed provocative, at least on the surface. It claimed that the conventional wisdom underlying pandemic flu preparations was wrong. It’s not the flu virus we should be defending ourselves against but the common bugs of the upper respiratory tract that take advantage of new fertile ground to grow in after the flu virus invades:
Medical and scientific experts now agree that bacteria, not influenza viruses, were the greatest cause of death during the 1918 flu pandemic.
Government efforts to gird for the next influenza pandemic – bird flu or otherwise – ought to take notice and stock up on antibiotics, says John Brundage, a medical microbiologist at the Armed Forces Health Surveillance Center in Silver Spring, Maryland.
Brundage’s team culled first-hand accounts, medical records and infection patterns from 1918 and 1919. Although a nasty strain of flu virus swept around the world, bacterial pneumonia that came on the heels of mostly mild cases of flu killed the majority of the 20 to 100 million victims of the so-called Spanish flu, they conclude.
“We agree completely that bacterial pneumonia played a major role in the mortality of the 1918 pandemic,” says Anthony Fauci, director of National Institute for Allergy and Infectious Disease in Bethesda, Maryland, and author of another journal article out next month that comes to a similar conclusion. (New Scientist)
It’s true that most flu experts agree that secondary bacterial pneumonias played a major role in the 1918 pandemic, so that’s not new. So what is new here? After examining the paper (you can find it here), I conclude: not much. And while it makes a point worth making, I’m not sure it makes it in the best way or draws the most important conclusion.
Here’s the main point of the argument. In 1918 an influenza virus swept the globe wreaking havoc and extraordinary morbidity and mortality. The case fatality ratio (CFR) has been estimated to be about 2%, give or take, which means that for every person with flu who died there were fifty who recovered. Since there were an awful lot of people who got flu in a relatively short period of time, an awful lot of people died in a short period of time as well. The fact that the number of cases and the number of deaths completely overwhelmed existing resources isn’t at all surprising. Currently our emergency rooms are taxed by ordinary flu seasons. A pandemic like 1918 would result in a catastrophic demand on services today, too, whatever the CFR. Brundage and Shanks, the authors of the EID article have a further point to make, however. There is a widespread notion that the 1918 virus was unusual, “hypervirulent,” that is, it wasn’t an ordinary flu virus but one that struck rapidly and lethally, producing a rapidly fatal primary viral pneumonia with accompanying acute respiratory distress syndrome (ARDS) accompanied by an acute dysregulation of the immune system in the form of a “cytokine storm.”
If you assume the main threat is a primary viral pneumonia then concentrating on means to prevent or treat the viral infection is the logical strategy, and indeed the medical response underlying pandemic plans emphasizes development of vaccines against possible pandemic influenza strains and antiviral agents like the neuraminisdase inhibitors, Tamiflu and Relenza. If the main problem, however, is secondary bacterial pneumonias then more emphasis would be given to vaccine against bacteria that cause pneumonia in flu patients (e.g., the pneumovax vaccine against Str. pneumoniae). This is a perfectly valid point and Brundage and Shanks go on to give reasons why they believe most deaths in 1918 were from secondary bacterial pneumonias rather than primary viral infections from a hypervirulent virus.
Their arguments are all perfectly plausible but highly circumstantial and in some cases not very weighty. For example, they consider the most cogent item the opinion of contemporary observers that most deaths were due to bacterial pneumonia, although these observations were made in an era prior to the discovery of the influenza virus. That a lot of smart people identified bacterial infection and isolated common respiratory tract bacteria from autopsy cases is neither surprising nor is it very informative. The same goes for virtually all their other arguments which rely on enough handwaving to generate a breeze that could knock you over.
Most people in 1918 who got flu didn’t die of it and the ones that did probably died mostly from secondary bacterial pneumonias. But now we have to ask what this has to do with today’s pandemic planning assumptions. In order to draw policy conclusions one has to make some additional assumptions. One is that a modern pandemic caused by the leading candidate, influenza A/H5N1 (“bird flu”), would be the like 1918 in character and severity. What we know about H5N1 to date is that differs from 1918 flu in two very important respects. One is that so far it isn’t very contagious. That’s the good difference. The bad difference is that so far H5N1′s CFR is a horrific 60% plus and much of the reason seems to be an associated ARDS. Even if the CFR is overestimated by a factor of ten (unlikely from the evidence to date, but possible) it would be three times worse than 1918. If the pathogenic mechanisms didn’t change — that is, if H5N1 behaved more like the small minority of 1918 cases that could be described as hypervirulent — then the magnitude of the task in treating and managing them would depend on what happens to transmissibility. That’s something we don’t know but it could potentially become much more transmissible while staying highly virulent (the idea that virulence and transmissibility must trade-off is wrong; they may or may not). It’s the serious cases that will tax the health care system and the society.
Still, the point is valid: don’t make the preparedness strategy all about the virus. But here’s where we start to part company with the authors. They suggest adding antibiotics and antibacterial vaccines to the mix because secondary pneumonias will be important, putting in place appropriate surveillance of antibiotic resistance and species prevalence. But that won’t solve the main problem which will be coping with the medical surge and the effects of widespread absenteeism. It’s not all about proper medical therapy, either. That’s important but if the medical care system isn’t able to handle most cases, also irrelevant. The medical care system and many other vital services is so brittle it won’t take much of a pandemic for them to break.
So point taken. But not far enough.