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.