Why you should care

Because fighting the world’s deadliest infectious diseases might require flipping our current strategy on its head.

A volunteer who serves the homeless at a free kitchen in Oakland, California, George Cash makes sure to get his flu shot every year — and every year, the impish-eyed former fireman spends the next few days suffering from flu-like symptoms. He feels sweaty and nauseous. He loses his appetite. With this year’s flu season in full swing, he says he can’t help but feel “wary.”

But one day, Cash may no longer need to experience these side effects, thanks to a recent shift in focus from viruses, bacteria and other invaders to patients and their symptoms instead. The big idea? Sometimes it’s not just a germ that throws the body into diseased disruption, but also the body’s own hyperactive response — its fevers, vomiting and aches. And so, the thinking goes, if you could calm, sedate or otherwise redirect the immune system, you could knock out many of the disease’s most pernicious effects. “It’s a paradigm shift,” says Conrad Liles, an associate chair of medicine at the University of Washington.

Best-case scenario? This new class of so-called immunomodulatory drugs could replace vaccines altogether and let Americans, 200,000 of whom are hospitalized with the flu every year, dispense with the annual ritual of getting a flu shot. While mass vaccination campaigns have proven effective for diseases like polio and the measles, they still typically protect against a few strains of the virus, which mutates very fast. In contrast, an immunomodulatory drug would span a spectrum of flu strains. Also, by the way, the drugs could be cheaper and more accessible to those in the developing world.

What if statins could treat the flu or Ebola?

Researchers still need to conduct large-scale clinical trials, of course. The handful of small human studies published so far have been mixed, and it’s not as though immunomodulators could be a panacea: They can’t prevent infection, have some side effects, like insomnia and the increased risk of liver damage, and could make it harder to boot the disease-causing agent from the body. On top of that, disease-causing invaders could still eventually adapt to immunomodulatory drugs and evolve in response. All of which is why experts say the most effective approach would likely involve using them alongside vaccines.

Scientists began investigating immunomodulation as an anti-flu strategy during the 2009 swine flu epidemic. Back then, autopsies revealed that victims who had suffered the worst symptoms had also experienced the strongest deluge of immune proteins called cytokines — a phenomenon dubbed the “cytokine storm.” That storm also raged in patients with infectious diseases like SARS, Ebola, malaria and sepsis. Since then, studies have shown evidence that the cytokine storm ravages the endothelial cells that envelop blood vessels — and can eventually cause fatal organ failure.

That’s why scientists have concluded that symptoms of some infectious diseases stem not only from the disease-causing agent — the virus or bacterium — but also from the patients’ own overzealous immune response. Targeting the proteins angiopoietin 1 and 2 can reverse endothelial damage. As it turns out, drugs like cholesterol-lowering statins and blood pressure-lowering angiotensin-receptor blockers (ARBs) do just that. What if they could also help treat infectious diseases like the flu or Ebola?

Sure enough, a study published in The Journal of Infectious Diseases in 2012 found that giving statins to patients hospitalized with seasonal flu significantly lowered their risk of death, while a Clinical Infectious Diseases study reported similar findings in pneumonia patients. And when physicians in Sierra Leone treated around 100 Ebola patients with a statin or ARB, only three died, David Fedson reported in the International Journal of Infectious Diseases earlier this year.

Experimental drugs that raise levels of the protein IFITM3 — which traps all known flu viruses — boosted resistance to infection in mice.

Fedson believes a “bottom-up” approach of targeting the immune system with such drugs could save more lives in an epidemic than conventional “top-down” strategies, like surveillance and vaccine development. In February, The New England Journal of Medicine reported that these had only a modest effect on the Ebola epidemic, with death rates in most treatment units hovering at or above 60 percent. Similarly, timely, affordable H1N1 vaccines and antivirals failed to reach more than 90 percent of the global population, Fedson noted in a 2013 Antiviral Research review article.

Scientists are also working to prevent flu infection in the first place — without a vaccine. Ohio State University researchers recently reported in PLOS Pathogens that experimental drugs that raise levels of the protein IFITM3 — which traps all known flu viruses and renders them unable to replicate — boosted resistance to infection in mice and human lung cells. Janet Waring, a volunteer nurse at St. Vincent de Paul, notes that such a drug “would need to be single-dose” to benefit the poverty-stricken individuals most susceptible to infection, many of whom struggle to maintain a strict medication regimen. But Cash, “still suspicious” of the existing vaccine’s side effects, remains optimistic about any alternative: “It’s a good move.”

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