Monday, October 15, 2012

The worst virus

kw: book reviews, nonfiction, medicine, viruses

What ancient disease is 100% fatal without treatment? For that matter, even more "modern" diseases such as Ebola and Marburg are not 100% fatal. This image shows the face of the most-feared disease in history.

These look like hollow-point bullets, but they are far worse. This is the rabies virus. It is rare enough in the First World that many doctors have never seen a case of human rabies. In the U.S., about 3 cases (fatalities) occur yearly, in spite of the existence of an effective treatment. However, worldwide, the death toll is about 55,000. Sad to say, that still makes it a "rare" disease, and in many countries there is little incentive to spend money to vaccinate all the dogs, or keep on hand sufficient amounts of the post-exposure vaccine to treat more than a fraction of the human cases.

The husband-wife team of Bill Wasik and Monica Murphy have written Rabid: A Cultural History of the World's Most Diabolical Virus. While there is medical information aplenty, the emphasis is on the effect of Rabies and other zoonoses on human society during at least the past 4,000 years. Rabies not only has a folklore all its own, the peculiar way the disease progresses has also spawned two major cultural threads: vampires and werewolves. I'll leave the details to your imagination.

The folk horrors are not based on human cases of Rabies, but on observations of dogs. The Mad Dog phenomenon is well known. Humans infected with the virus, once it reaches the brain, exhibit hydrophobia, but very rarely bite or attack others. Also, the saliva of human cases contains little of the virus. Humans are dead-end hosts. The two hosts most responsible for spreading the disease are dogs and bats, although the virus can infect any mammal, and any mammal can catch it from any infected mammal, although I suspect a mouse or shrew would have a hard time piercing the skin of an elephant or rhino and infecting it.

The course of infection is unusual, and fortuitously led to a way to produce a post-exposure vaccine for humans, developed by Louis Pasteur in 1880-85. A bite, whether by dog, bat, raccoon or skunk (the most common hosts), deposits virus-laden saliva in the wound. Immediate cauterization is known to destroy the contagion, and this is the only historical remedy that has any chance of working. It is still used in the Third World. Within a day or so, however, the virus particles have found their way to a nerve and are making their way toward the brain. They travel at a rate of about 2 cm per day, so a bite on the hand or food could be dealt with by amputation, but this seems to be very rare. Once the viruses reach the brain, death is certain, in an average of four days.

The Milwaukee Protocol, developed by Dr. Rodney Willoughby in 2004, offers only a smidgen of hope. That is the year a girl survived brain infection with Rabies, while a medically induced coma and intensive supportive therapy kept her alive as her body developed an immune response strong enough to drive out the virus. Since that time about 8% of patients given this therapy have survived. A 92% death rate is marginally better than a 100% death rate.

The Pasteur vaccine and more recent (and less painful) vaccines develop the body's immune response during the time of nerve transmission, preventing the virus from reaching the brain. These vaccines, and the preventive vaccine given to most dogs in the West, are responsible for the very low Rabies death rate here. If 70% of dogs worldwide could be vaccinated, and human vaccines were made globally available, the world incidence of Rabies death would be about 70. To reduce it further would require some kind of vaccination program for raccoons and skunks and bats. How would you vaccinate billions of bats?

Rabies is but one of many zoonoses, or human diseases that originated in animals. I suspect all human diseases actually began as zoonoses. The ones most anciently associated with us began when we were another species! They evolved along with us. The most familiar zoonosis is influenza. Many kinds of flu virus circulate among birds and swine, in particular, but also among other animals. Most years, the Northern winter season leads to a sweep of flu across the globe and claims as many as half a million lives worldwide. The 1918 "Spanish flu" (that originated in swine) was unusually virulent and killed 40 million worldwide. For a sense of scale, malaria kills between 700,000 and 1.2 million yearly, depending on which "authority" you believe. The most famous recent zoonosis is AIDS, which seems to have jumped the ape-human barrier several times in the early 1900s, and now kills about 2 million yearly, having outstripped malaria since the 1980s.

In the book's closing chapter, the authors introduce an interesting twist. Knowing that the Rabies virus crosses the blood-brain barrier, how does it do it? Diseases such as meningitis, once they get into the brain, are usually fatal, and brain infections in general are intractable because none of our antibiotics can get into the brain except by direct injection. Who wants to have a hole bored in their skull? (I do, if it will save my life!). Pieces of the Rabies virus envelope can apparently hitchhike into the brain on "trusted" proteins. Thus this most fearsome of diseases may soon be harnessed to help us conquer other brain infections.

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