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O CDC de Atalanta …intrigado ! Deveras interessante.
Houston rabies case poses new questions about age-old illness
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At the US Centers for Disease Control and Prevention [CDC], she’s
called the “Texas wild child.” She was a 17-year-old who had run away
from home when she walked into a Houston hospital with a fever and
puzzling neurological symptoms. Her name is veiled by medical privacy
laws, as is the identity of her family back in Missouri; exactly how
she was exposed to the virus that sickened her 3 years ago is a
mystery. Where she is now, no one seems to know. Her disappearance is
part of one of the area’s most intriguing medical mysteries: The CDC
says she is the only known person in the US to survive rabies after
the onset of clinical symptoms, and without prior vaccination or
intensive hospital care.

“Obviously we’re dying to know what happened to her,” said Dr Charles
Rupprecht, who leads the CDC’s rabies program in Atlanta. “We made
calls to the numbers she gave us, but she’s dropped off the grid.” To
Rupprecht, the Texas case is “the door that’s been opened” to
questioning the age-old paradigm of rabies. What if the one thing we
thought we knew about this disease — once contracted, it is a certain
death sentence — isn’t true? “Rabies is one of the few diseases that
we thought we understood, and now we have to undo that,” said Dr Carol
Glaser, who leads the special investigations division of the
California Department of Public Health. “When you think about it, no
other infection has a 100 percent mortality rate. Why should this?”

There have always been clues. Veterinarians know that not all animals
die after exposure — usually from a bite — to the rabies virus,
which is carried in saliva and other bodily fluids. Much depends on
how much of the virus is transmitted, the severity and location of the
bite, and the immune system of the bitten animal. “Abortive rabies is
not unusual in research animals — it happens spontaneously all the
time,” Rupprecht said. [For example, see: Hamir AN, Niezgoda M,
Rupprecht CE: Recovery from and clearance of rabies virus in a
domestic ferret. J Am Assoc Lab Anim Sci. 2011 Mar; 50(2): 248-51;
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3061427. – Mod.CP]
Rupprecht said the blood of certain human populations — maybe 1
percent of raccoon hunters, for example — also tests positive for
rabies antibodies, indicating they have been exposed to the virus
without becoming acutely ill. In the Amazon, where indigenous tribes
are at daily risk of rabies from vampire bats, “it could be in the 10
percent or more range,” he said.
The rabies vaccine, injected in a series of 5 doses, prevents onset of
the disease if given soon enough after exposure. About 35 000 people
receive the expensive shots — the series costs about USD 1600 — in
the US each year. Seldom do more than a handful of people die from
rabies in a year. But once rabies symptoms appear, the vaccine is no
help. “We don’t have poster children. In our field, 99.9 percent of
our cases are in the ground,” Rupprecht said. In that grim fact lies
the significance of the unidentified Texas teenager. The CDC published
her case in February 2010, calling it the 1st reported instance of
abortive human rabies [Presumptive abortive human rabies – Texas,

  1. MMWR Morb Mortal Wkly Rep. 2010 Feb 26; 59(7): 185-90.
    http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5907a1.htm. See Abstract
    reproduced below. – Mod.CP] Though her blood and cerebral spinal fluid
    tested positive for rabies exposure, she never became critically ill,
    and never even needed extraordinary treatment. She recovered and left
    Children’s Memorial Hermann Hospital in Houston under her own steam.
    “Nobody does that. She broke an immunological rule,” said Dr Rodney
    Willoughby of Children’s Hospital of Wisconsin. “It’s almost
    liberating.” Dr Tom Sidwa, who heads the Texas Health Department’s
    rabies program, said public health authorities must now view possible
    rabies cases differently. “Prior to this girl in Houston, anything
    that suggested improvement, they said, ‘That ain’t rabies,’?” he said.
    “They can’t say that anymore.”

Rabies is [caused by] a lyssavirus, a zoonotic brain infection —
meaning it can pass from animals to humans and vice versa — that is
so old and so feared, it has its own mythology. Lyssa was the Greek
goddess of rage and mad dogs; scholars have noted the parallels
between vampire legends and symptoms of rabies in humans, such as
biting, extreme sensitivity to light, and occasionally,
hypersexuality. The disease figures in popular novels (think “Cujo”
and “Old Yeller”) and movies (for instance, “Rage” in 1966 and the
2010 Israeli horror film, “Kalavet”). “This is something out of your
nightmares — it’s very primal,” Rupprecht said. “Rabies and horror
are deeply ingrained in our psyche.”

Until Louis Pasteur developed a vaccine in 1885, there was no
prevention. There is still no cure for rabies, which has an uncommon
ability to subvert the body’s immune system until infection is so far
advanced that death is inevitable. The World Health Organization
estimates that rabies kills 50 000 people annually, most of them
bitten by mad dogs in Africa and Asia. Thanks to widespread
vaccination of pets, there have been only 108 cases of human rabies in
the US in the past 50 years. Texas and California, with 19 and 20
cases respectively, have had the most. Before the Houston case in
2009, there were just 6 well-documented survivors of rabies worldwide,
according to the CDC. 5 received vaccinations before becoming ill. All
were left with some degree of neurological damage.

The 6th, most famous survivor is Willoughby’s former patient, J.G. A
month after being bitten by a bat in Fond du Luc, Wisconsin, in 2004,
the 15-year-old girl was hospitalized with vomiting, slurred speech,
tremors, and excessive salivating. The CDC confirmed rabies-specific
antibodies in her spinal fluid. It was too late for the vaccine.
Willoughby, a pediatric infectious disease specialist, had seen rabid
dogs while growing up in South America, but never a human with the
disease until she “just landed in my lap,” he said. He had only hours
to read up on rabies on the Internet. Scrolling through medical
journal articles from all over the world, he saw that post-mortem
exams often showed surprisingly little evidence of damage to the brain
from rabies. The killing thing seemed to be violent disturbances of
brain function that had caused the autonomic nervous system to go
haywire. “It was a software problem,” Willoughby said. He reasoned
that if he shut down the nervous system long enough to prevent a
meltdown, it might buy time for the “cavalry” — the immune response
— to arrive. “It’s such a simple concept you wonder why no one had
thought of that before,” he said. He told the girl’s parents they
could put their daughter in hospice care to await certain death, or
allow her to be drugged into a coma, hooked up to life support, and a
cocktail of antiviral medicines — an untested regimen that was likely
to fail. It was an easy choice.

The girl became the 1st unvaccinated survivor of rabies the world has
known. She suffered minimal neurological effects, and in 2010 she
graduated from college. Yet, no sooner had Willoughby published her
case than physicians worldwide questioned whether his radical
treatment — now called the Milwaukee protocol — made sense. Doctors
in developing countries have seen thousands of rabies patients and
lost them all. They were skeptical of a single rogue case in the US
that relied on a dream team of specialists and high-tech supportive
care. What proved that the medical coma had worked? Where were the
animal studies that supported it? What if the Wisconsin girl never had
full-blown rabies to begin with? Since that 1st success, 4 other
people around the world — all of them young and unvaccinated — have
contracted rabies and survived after medically-induced comas,
Willoughby said. The latest was an 8-year-old girl in Humboldt County,
California, who fell ill last year [2011]. But 32 other rabies victims
who were subjected to the protocol have died, including a 16-year-old
high school football player in Humble who was bitten by a bat in 2006.
The most recent is a 63-year-old man in Cape Cod, Massachusetts, who
succumbed in January [2012], also after a bat bite. “We made something
up and it worked,” Willoughby said. “Getting it to work again —
that’s been much harder. Either we’re doing something right, or we’re
just lucky.”

The wisdom — and extraordinary expense — of the Milwaukee protocol
has been challenged in the very places where rabies is rampant. In
Southeast Asia, where an estimated 24 000 people die each year from
the virus, doctors tried it on a single patient without success in

  1. “The cost for caring for this patient by a multi-specialist team
    at a university hospital in Thailand could have provided pre-exposure
    rabies vaccination … for at least 16 000 slum-dwelling children in
    Bangkok,” they wrote in the journal of the Royal Society of Tropical
    Medicine and Hygiene. The doctors decided not to subject future
    patients “to intensive therapeutic measures, including respiratory and
    cardiovascular support. Symptomatic and comfort care … will be the
    primary goal for many patients.” “We’re on the horns of an ethical
    dilemma,” Rupprecht said. “But whenever you get the phone call from
    someone who says, ‘Please save my child,’ what are you going to do?”

For centuries, Europeans knew rabies as a disease primarily spread by
dogs, wolves, and other canines. Not until the 1950s did scientists
discover that the virus is carried by insect-eating North American
bats (including the Mexican free-tail bats that nest by the millions
in Central Texas, not the vampire bats of South America), which are
now the most common cause of human exposure to rabies in the state and
much of the US.

The story of that discovery is told in “The Incurable Wound,” a 1957
New Yorker article that is a classic among medical students and
infectious disease specialists. It begins with a West Texas farmer’s
wife who died of rabies after being bitten by a bat she found lying in
the road. It ends with another Texas casualty, a state health
department epidemiologist named George Menzies who succumbed to the
disease after collecting bat specimens from caves in the Hill
Country.

Despite the frequency of rabies in Texas â?” in 2010 and 2011 Texas
led the nation in reported cases in animals â?” no one initially
thought of the disease in March 2009 as Houston doctors puzzled over
their 17-year-old patient, a few blocks from another hospital where a
boy her age had died of rabies three years earlier. The girl had
severe headaches, neck pain and vomiting. Light hurt her eyes. She was
agitated and combative.

The tentative diagnosis: infectious encephalitis, a brain inflammation
of uncertain origin. Under questioning by her doctors, she revealed
she had been camping somewhere between Austin and San Antonio two
months before, and had entered a cave where flying bats had brushed
against her. She didn’t think she had been bitten, but samples of her
blood and spinal fluid were rushed to the CDC anyway.

Four samples tested positive for rabies antibodies. Doctors gave her a
single dose of rabies vaccine before halting the series of five shots,
afraid the vaccine would complicate her own immune response.

Slowly but surely, their patient got better and was discharged three
weeks later, seemingly recovered. Over the next few days, she returned
twice more to the emergency room with headaches, but her symptoms
again resolved and she was not readmitted.

It was the last they were to see of her. During her treatment, the
young woman turned 18 and so by law was then an adult in charge of her
own medical care. According to Dr. Anthony Eshofonie, an
epidemiologist who was working for the Houston Health Department at
the time, she rebuffed attempts by medical personnel to keep track of
her.

“She and her boyfriend were more concerned about their privacy than
their health consequences,” he said.

“She changed her phone, changed her email. She’s what we call â?~lost
to follow-up,’â??” Rupprecht said.

Attempts by the American-Statesman to reach her physician at
Children’s Memorial also failed. A hospital spokesperson said doctors
cannot comment on cases without patient consent.

Asked why the CDC did not try harder to find someone who could alter
the scientific understanding of rabies, Rupprecht said the agency’s
hands were tied. “We’re big believers in states’ rights and personal
freedom. The patient has the right to be left alone.”

Twenty miles from the hospital where she was treated, at the
University of Texas Medical Branch in Galveston, research is now under
way to test the effectiveness of the treatment credited with Jeanna
Giese’s recovery from rabies. The test animals are ferrets, in which
rabies closely mimics the form seen in humans.

The idea is to standardize the Milwaukee protocol â?” what length of
coma to induce, which antivirals to use â?” so that it could be used
anywhere, said Dr. Nigel Bourne, the researcher in charge of the
project, which is funded by the National Institutes of Health.

But progress has been slow. It’s hard to anesthetize ferrets for days
at a time without killing them, and each animal must be monitored 24
hours a day, as if it were in intensive care. “I would like to tell
you we’ve solved all the problems, but we haven’t,” he said.

In the parts of the world where rabies is most prevalent, children are
most often the victims. “I’m in pediatrics â?” that’s one of the
reasons we’re doing this work,” Bourne said.

Meanwhile, in Wisconsin, Willoughby still takes calls from doctors
around the globe. Sometimes they send Willoughby videos of their
patients, dark-eyed children with only days to live. Desperately
thirsty, they choke violently when they try to drink a cup of water
and push it away. Involuntary throat spasms are a telltale sign of
rabies and the origin of its scientific name, hydrophobia â?” fear of
water.

You can see some of these videos on YouTube. They are disturbing,
heartbreaking. They show that far from being lost to madness, victims
are conscious of their surroundings and what is happening to them. And
they help explain the desire to pull out all the stops to save even
one of the thousands of doomed patients, wherever they are.

“It is terrible, truly terrible,” Willoughby said. “I hate this
disease.”

[Byline: Brenda Bell]


Communicated by:
ProMED-mail
promed@promedmail.org

[A description of the “Texas wild child” case was published in MMWR
Morb Mortal Wkly Rep. 2010 Feb 26; 59(7): 185-90;
http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5907a1.htm. Entitled ”
Presumptive abortive human rabies – Texas, 2009,” the abstract is
reproduced below.

“Rabies is a serious zoonotic disease. Recovery has been well
documented in only 6 human patients worldwide. 5 of those patients had
received rabies vaccinations before illness; one had not received
rabies vaccination but survived infection after prolonged intensive
care. In most of these survivors, moderate to profound neurologic
sequelae occurred. In all 6 survivors, rabies was diagnosed based on
exposure history, compatible clinical symptoms, and detection of
rabies virus-neutralizing antibodies (VNA). This report describes the
clinical course and laboratory findings of an adolescent girl with
encephalitis who had not had rabies vaccination and who had been
exposed to bats 2 months before illness. Antibodies to rabies virus
were detected in specimens of the girl’s serum and cerebrospinal fluid
(CSF) by indirect fluorescent antibody test (IFA). However, the
presence of rabies VNA was not detected until after she had received
single doses of rabies vaccine and human rabies immune globulin
(HRIG). Although the patient required multiple hospitalizations and
follow-up visits for recurrent neurologic symptoms, she survived
without intensive care. No alternate etiology was determined, and
abortive human rabies (defined in this report as recovery from rabies
without intensive care) was diagnosed. Public education should
emphasize avoiding exposure to bats and other potentially rabid
wildlife and seeking prompt medical attention after exposure to such
animals. Rabies is preventable if rabies immune globulin and vaccine
are administered soon after an exposure; however, this case also
suggests the rare possibility that abortive rabies can occur in humans
and might go unrecognised.”

The Austin American-Statesman article above provides a useful summary
of the present state of knowledge concerning abortive rabies virus
infection, and which may elicit further information concerning the
enigma of the Texas patient. – Mod.CP

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