See-Through Zebrafish Offer a Window Into the Chilling Creep of Meningitis

A uniquely unpleasant way to go.

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Oct 1 2015, 10:00am

Image: Duke University

Meningitis doesn't get nearly the attention it deserves, at least compared to nature's many other cruel and not so unusual illnesses. Largely credit the fact that among healthy first-world populations, the infection is rare; globally, however, it kills around 600,000 people annually. That's about how many people die annually in the US from its leading killer: heart disease.

The various forms of meningitis (viral, bacterial, fungal) prey on those with weak immune systems: children, the elderly, and those with existing illnesses. HIV patients and and organ-transplant patients are a particularly at-risk group.

The cruelty of meningitis largely has to do with its assault on the nervous system. Whatever the precise source of infection, the result is an often catastrophic swelling of the tissues surrounding the brain and spinal column. With help from conveniently see-through zebrafish larvae, researchers at Duke University have now captured in eerie detail the front-lines of a battle for the brain of an organism infected by the cryptococcus fungus. This is meningitis in action.

The name cryptococcus derives from "hidden sphere" and, indeed, the fungus persists as tiny balls, the more benign forms of which are sometimes found buried in soil. In the videos, cryptococcus cells are the red guys, while the blue spheres are macrophages. You can sort of see the macrophages give chase to the invading fungal cells—futilely it seems.

"What's impressive is that, unlike in a mouse or rabbit, you can actually see the organism producing disease in the live animal," said John R Perfect, an infectious disease specialist and co-author of a new study describing the zebrafish imaging technique, in a statement. "Day-by-day, it's growing and moving throughout the body. You can't see this anywhere else."

As the infection progresses in a human host, non-specific symptoms such as fever and headache give way to common meningitis warning signs, such as stiff neck, nausea and vomiting, photophobia (sensitivity to light), and altered mental status. Untreated, the infection will go on to cause coma, brain damage, and eventually death. It's not an especially pleasant progression.

Cryptococcus infections are treatable, largely thanks to a drug known as flucytosine. Flucytosine is generic and quite old, but, like current outrage drug Daraprim, is what's known as a "market failure." That is, despite being generic, the drug has only a single approved manufacturer. Other manufacturers could concoct a generic version, but don't. Its target market, largely HIV patients vulnerable to opportunistic infections, doesn't scream dollar signs.

As a result, an individual within that target market is faced with a tab of around $10,500 to $21,000 for a two-week treatment course. (Based on a price of about $40 per 500 mg pill and 50 to 150 mg per kilogram taken daily for a 100 kilogram patient.)

In any case, the zebrafish imaging technique demonstrated here can be used generally, offering new insights into not just cryptococcus infections, but all sorts of gnarly things, including other fungal and bacterial infections. That's no promise of cheaper treatments, but one can imagine some future new and improved antifungal treatment that doesn't require swallowing 20 or so pills every day for two weeks. That would be helpful.