A pox on your house? How fighting one disease brought back another

Some were surprised to read that after a pro basketball player swatted a bat out of the air, he had to have rabies vaccinations.

This is not a surprise to many medical folks who have had to give rabies prophylaxis after bat exposures. Most of the few human rabies cases in the U.S. are transmitted by bats, although raccoons are more often diagnosed with the disease. Because rabies is fairly easy to transmit and nearly always fatal to humans, we are very aggressive about prevention. Rabid wild animals can have unusually aggressive behavior and can transmit rabies to humans and to their pets. With human populations mixing more and more freely with wild animal populations, the risk of rabies exposures increases. We're obviously not about to hold down every wild raccoon and vaccinate them, but humans, being rather clever animals, have found a way to vaccinate animals in high-risk areas.

One program aims to create a "vaccine barrier" in the Appalachians by dropping oral rabies vaccines into these areas either by plane or by hand. The program is aimed primarily at raccoons but other animals are affected as well. The vaccine itself is fiendishly clever, but, as the CDC reports, is not without some unintended results.

The vaccine was created by taking a glycoprotein antigen from the rabies virus and inserting it into Vaccinia virus, the same one used for smallpox inoculation.  Further explanation requires a historical digression.

Smallpox killed and disfigured millions of people around the world until its eradication in 1979 through a massive vaccination program. It is unclear when parts of Asia and Asia Minor began using immunotherapy to prevent smallpox deaths, but in the early 18th century, Lady Mary Worthley Montagu, an English aristocrat stationed in Istanbul, made note of the practice and brought it back to England.

In these pre-vaccination days, smallpox pustules would be lanced, and their contents inserted into the skin of healthy people, producing a (hopefully) minor, localized infection which would then protect people from severe smallpox infection. Smallpox inoculation saved many lives but was not without risk. Later in the century, Edward Jenner developed the practice that ultimately replaced it: vaccination. This practice was based on the observation that milkmaids previously infected with cowpox ("vaccinia"), a usually-minor infection in humans, were relatively safe from smallpox. Two hundred years later, smallpox was gone.

Vaccinia is not one of the safer vaccines. In people with defective immune systems, the normally mild infection can be severe, so eradicating smallpox not only saved people from smallpox but from needing the vaccine (it is still used in specialized settings such as the military). But vaccinia has not outlived its usefulness.

How do you vaccinate millions of wild animals? Most vaccines must be injected, but there are exceptions, such as the human oral polio vaccine. In this case, a little genetic engineering convinced vaccinia to produce an important rabies antigen. When eaten, the virus in taken up in the lymphatic tissue in the throat, and immunity to rabies develops. The vaccinia infection caused by the vaccine is usually mild and transient.

So in areas where it's needed, little ketchup package-shaped vaccines are dropped from planes or spread by hand. They are wrapped in tasty fishmeal, and animals readily bite into them. But raccoons aren't the only curious animals out there. Dogs are pretty curious, too.  Because this vaccine contains a live virus, the CDC maintains a surveillance system to watch for human infections. They found one.

A woman in Pennsylvania was out picking berries when her dog brought her a vaccine packet it had found. Some of the vaccine material dripped on to her hands which had been abraded by the berry brambles. She was perfectly inoculated by the special vaccinia virus. In most people, this would only be of passing interest, but the woman suffers from inflammatory bowel disease and takes powerful drugs to suppress her immune system. Within four days of exposure, she had pox on her hand.


Photo from the CDC, via Dr. C. Encarnacion.

She sought help even before she developed the rash so doctors were able to track her disease carefully.  Unlike normal patients, she did not develop antibodies to fight her infection, and it started to spread.  Her immunosuppressive medications were stopped, and she was treated with specific immunoglobulin treatments and recovered without lasting ill effects.

This case of human vaccinia infection is notable for it's rarity.  Only one other person has ever developed an infection from the vaccine.  The rabies problem is real, and this is a fascinating solution, but as the CDC points out, education needs to improve in areas where the vaccine is used.  

This one case walks us from Lady Worthley Montagu's 18th century observations, to Jenner's discovery, the eradication of smallpox, and the co-opting of the same organism via recombinant DNA techniques to help fight an entirely different disease.  Science doesn't get any more interesting than this.


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Here in Arizona a bat strain of rabies has changed through mutation or genetic drift so that it can spread more easily in other species such as foxes and skunks. The CDC and USDA wildlife services have been using the oral vaccine and trapping and vaccinating skunks (apparently the oral vaccine is not effective in skunks for some reason) to try to prevent the evolution of a new strain in wildlife. I posted about it this spring after a particularly bad National Geographic article made people think that the Rabies virus had changed and started to spread via an airborne route.
The technology used to develop the oral rabies and the ability to monitor genetic drift and mutation in the different variants of rabies virus are fascinating. The USDA also started trapping and monitoring bats this summer to try to track down the reservoir for rabies in this area.

Now there's a zebra. Smart lady to get checked out right away. Presumably, notwithstanding her immunosuppressive therapy, she's now at least partly immune to both rabies and smallpox.

That's pretty fascinating. If I had pox like that showing up I'd probably think I had some how managed to get small pox and have a nervous breakdown.

Presumably, notwithstanding her immunosuppressive therapy, she's now at least partly immune to both rabies and smallpox.

Actually, the MMWR report had this interesting bit:

The patient remained Orthopoxvirus IgM
negative throughout her illness.

So I guess I wouldn't assume she's safe from smallpox.

I live in an area (eastern Ontario) that had one of the highest rates of rabies endemism in North America due to the Arctic Strain that was widespread amongst our foxes and also seen in other animals. The OMNR oral vaccination campaign (vaccine baits were dropped from planes) pretty much wiped it out. It was a great success. Unfortunately we now have Raccoon rabies coming in from New York. I'm not sure what the prognosis for a successful intervention is on that front if it does become established.

WTF? Why did the basketball player swat the bat out of the air? Because he could? What a dick. Serves him right.

Seriously, Strider? Maybe because there's a potentially infectious animal disrupting a game and endangering a stadium full of people?

Read the article before you judge next time.

"endangering a stadium full of people?" Hyperbole much?

Thank you for an interesting, excellent post.

By Catharine (not verified) on 07 Nov 2009 #permalink

Is the rabies glycoprotein recognized by TLR2? I'm wondering about whether inflammatory monocytes are activated by this, and produce type I interferons, and whether that is typical of a rabies response or not (I'd guess not, since I think rabies is toxin-mediated, and those are often deadly without the immune system going haywire).

Yah, Twewi? Bats are not disease carrying vermin to be feared and destroyed. Not all carry rabies. Notice Pal mentioned prevention and not treatment for the b-ball player. The basketball player could've waited for somebody with a net to catch it and NOT swatted it down.