Re: 1st case of extremely drug-resistant (XXDR) in USA found in 2007
http://www.promedmail.org/pls/otn/f..._BACK_PAGE,F2400_P1001_PUB_MAIL_ID:1000,80692
Archive Number 20091230.4387
Published Date 30-DEC-2009
Subject PRO/EDR> Tuberculosis, XXDR - USA: FL ex Peru
TUBERCULOSIS, XXDR - USA: FLORIDA ex PERU
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A ProMED-mail post
<http://www.promedmail.org>
ProMED-mail is a program of the
International Society for Infectious Diseases
<http://www.isid.org>
Date: Sun 27 Dec 2009
Source: MSNBC [edited]
<http://abcnews.go.com/Health/wireStory?id=9427607>
It started with a cough, an autumn hack that refused to go away. Then
came the fevers. They bathed and chilled the skinny frame of a
19-year-old Peruvian man visiting to study English. His lungs
clattered; his chest tightened, and he ached with every gasp. During
a wheezing fit at 4 a.m., he felt a warm knot rise from his throat.
He ran to the bathroom sink and spewed a mouthful of blood. I'm
dying, he told himself, "because when you cough blood, it's something
really bad." It was really bad, and not just for him.
Doctors say his incessant hack was a sign of what they have both
dreaded and expected for years, this country's 1st case of a
contagious, aggressive, especially drug-resistant form of
tuberculosis. The Associated Press learned of his case, which until
now has not been made public, as part of a 6-month look at the
soaring global challenge of drug resistance.
His strain -- so-called extremely drug-resistant (XXDR) TB -- has
never before been seen in the U.S., according to Dr. David Ashkin,
one of the nation's leading experts on tuberculosis. XXDR
tuberculosis is so rare that only a handful of other people in the
world are thought to have had it. "He is really the future," Ashkin
said. "This is the new class that people are not really talking too
much about. These are the ones we really fear, because I'm not sure
how we treat them."
"Drug resistance is starting to be a very big problem. In the past,
people stopped worrying about TB, and it came roaring back. We need
to make sure that doesn't happen again," said Dr. Thomas Frieden,
director of the U.S. Centers for Disease Control and Prevention, who
was himself infected with tuberculosis while caring for
drug-resistant patients at a New York clinic in the early '90s. "We
are all connected by the air we breathe, and that is why this must be
everyone's problem."
This April [2010], the World Health Organization sounded alarms by
holding its 1st drug-resistant TB conference in Beijing. The message
was clear; the disease has already spread to all continents and is
increasing rapidly. Even worse, WHO estimates only one percent of
resistant patients received appropriate treatment last year [2008].
"We have seen a huge up-burst in resistance," said CDC epidemiologist
Dr. Laurie Hicks.
The man's strain of TB puzzled doctors. He had never had TB before.
Where did he pick it up? Had he passed it on? And could they stop it
before it killed him? At first, mainstream doctors tried to treat
him. But the disease had already gnawed a golf-ball-sized hole into
his right lung. TB germs can float in the air for hours, especially
in tight places with little sunlight or fresh air. So every time he
coughed, sneezed, laughed or talked, he could spread the deadly germs
to others. "You feel like you're killing somebody, like you could
kill a lot of people. That was the worst part," he said.
Tuberculosis is the top single infectious killer of adults worldwide,
and it lies dormant in one in 3 people, according to WHO. Of those,
10 percent will develop active TB, and about 2 million people a year
will die from it. Simple TB is simple to treat, as cheap as a USD 10
course of medication for 6-9 months. But if treatment is stopped
short, the bacteria fight back and mutate into a tougher strain. It
can cost USD 100 000 a year or more to cure drug-resistant TB, which
is described as multi-drug-resistant (MDR), extensively
drug-resistant (XDR) and XXDR.
There are now about 500 000 cases of MDR tuberculosis a year
worldwide. XDR tuberculosis killed 52 of the 1st 53 people diagnosed
with it in South Africa 3 years ago. Drug-resistant TB is a "time
bomb," said Dr. Masae Kawamura, who heads the Francis J. Curry
National Tuberculosis Center in San Francisco, "a manmade problem
that is costly, deadly, debilitating, and the biggest threat to our
current TB control strategies."
The 19-year-old man underwent 3 months of futile treatment in a Fort
Lauderdale hospital. Then in December 2007, he was sent to A.G.
Holley State Hospital, a 60-year-old massive building of brown
concrete surrounded by a chain-link fence, just south of West Palm
Beach. "They told me my treatment was going to be 2 years, and I have
only one chance at life," He said. "They told me if I went to Peru,
I'm probably going to live one month, and then I'm going to die."
Holley is the nation's last-standing TB sanitarium, a quarantine
hospital that is now managing new and virulent forms of the disease.
[In] 1944, a critically ill TB patient was given a new miracle
antibiotic and immediately recovered. New drugs quickly followed.
They worked so well that by the 1970s in the U.S., it was assumed the
disease was a problem of the past.
Once public health officials decided TB was gone, the disease was
increasingly missed or misdiagnosed. And without public funding, it
made a comeback among the poor. Then immigration and travel
flourished, breaking down invisible walls that had contained TB. Drug
resistance emerged worldwide. Doctors treated TB with the wrong drug
combinations. Clinics ran out of drug stocks. And patients cut their
treatment short when they felt better, or even shared pills with
other family members. There are 2 ways to get drug resistant TB. Most
cases develop from taking medication inappropriately. But it can also
be transmitted like simple TB, a cough or a sneeze. In the 1980s, HIV
and AIDS brought an even bigger resurgence of TB cases. TB remains
the biggest killer of HIV patients today.
For decades, drug makers failed to develop new medicines for TB
because the profits weren't there. With the emergence of resistant
TB, several private drug companies have started developing new
treatments, but getting an entire regimen on the market could take 24
years. In the meantime, WHO estimates each victim will infect an
average of 10 to 15 others annually before they die.
A.G. Holley was back in business. Only 50 beds are funded today, but
those are mostly full. More than half the patients are court-ordered
into treatment after refusing to take their meds on the outside. The
19-year-old patient came voluntarily. In the beginning, he was
isolated and forced to wear a mask when he left his room. He could
touch his Peruvian family only in pictures taped to the wall. He
missed his dad, his siblings, his dog, his parrot, and especially his
mother. "I was very depressed," he said. "I had all this stuff in my
mind." He spent countless hours alone inside the sterile corner room
reserved for patients on extended stays, dubbed "the penthouse"
because it is bigger and lined by a wall of windows.
Early on, the man's treatment was similar to chemotherapy. Drugs were
pumped into his bloodstream intravenously 3 times a day, and he
choked down another 30 pills, including some that turned his skin a
dark shade of brown. He swallowed them with spoonfuls of applesauce,
yogurt, sherbet and chocolate pudding, but once they hit his stomach,
waves of nausea sometimes sent him heaving. He would then have to
force them all down again.
"When he first came in, we really had to throw everything and the
kitchen sink at him," said Ashkin, the hospital's medical director,
who experimented on the man with high doses of drugs, some not
typically used for TB. "It was definitely cutting edge and definitely
somewhat risky because it's not like I can go to the textbooks or ...
journal articles to find out how to do this."
After 17 years of handling complex cases -- including TB in the brain
and spine -- Ashkin had never seen a case so resistant. He believed
he would have to remove part of the man's lung. The 19-year-old man's
adventure in the U.S. had turned into a medical nightmare.
About 60 million people visit the U.S. every year, and most are not
screened for TB before arrival. Only refugees and those coming as
immigrants are checked. The top category of multidrug-resistant
patients in the U.S. -- 82 percent of the cases identified in 2007 --
were foreign-born patients, according to the CDC.
The results are startling among those tested, said Dr. Angel
Contreras, who screens Dominicans seeking to enter the U.S. on
immigrant visas. The high rate of MDR-TB in the Dominican Republic
coupled with high HIV rates in neighboring Haiti are a health crisis
in the making, he said. "They're perfect ingredients for a disaster,"
he said. The patient's homeland, Peru, is also a hotspot for
multidrug-resistant TB. DNA fingerprinting linked his disease to
similar strains found there and in China, but none with the same
level of resistance. "So the question is: Is this a strain that's
evolving? That's mutating? That's becoming more and more resistant?"
asked Ashkin. "I think the answer is yes." Doctors grappling with
these new strains inadvertently give the wrong medicines, and so the
TB mutates to become more aggressive and resistant.
Poor countries also do not have the resources to determine whether a
patient's TB is drug-resistant. That requires sputum culturing and
drug-susceptibility testing, timely, expensive processes that must be
performed in capable labs. WHO is working to make these methods more
available in high-risk countries as well as negotiating cheaper
prices for 2nd-line drugs.
"There's a lot of MDR and XDR-TB that hasn't been diagnosed in places
like South Africa and Peru, Russia, Estonia, Latvia," said Dr. Megan
Murray, a tuberculosis expert at Harvard. "We think it's a big public
health threat." Experts argue if wealthy countries do not help the
worst-hit places develop comprehensive TB programs, it puts everyone
at risk. "You're really looking at a global issue,'" said Dr. Lee
Reichman, a TB expert at the New Jersey Medical School Global
Tuberculosis Institute. "It's not a foreign problem; you can't keep
these TB patients out. It's time people realize that."
The 19-year-old patient spent a year and a half living alone in a
room plastered with bikini-clad blondes, baseball caps and a poster
of Mt. Everest for inspiration. When put side by side, his CAT scans
from before and after treatment are hard to believe. The dark hole is
gone, and only a small white scar tattoos his lung. "They told me the
TB is gone, but I know that TB, it doesn't have a cure. It only has a
treatment like HIV," he said, his English now fluent and his body
weight up 32 pounds from when he 1st arrived. "The TB can come back.
I saw people who came back to the hospital twice and some of them
died. So, it's very scary."
His treatment cost Florida taxpayers an estimated USD 500 000, a
price tag medical director Ashkin says seems like an astronomical
amount to spend on someone who's not an American citizen. But he
questions how the world can afford not to treat this patient and
others sick with similar lethal strains. "This is an airborne spread
disease ... so when we treat that individual, we're actually treating
and protecting all of us," he said. "This is true homeland security."
In July 2009, at age 21, 19 months after checking in, the man
swallowed his last pills, packed a few small suitcases and wheeled
them down the hospital's long corridor. The last time doctors saw
him, he was walking out of the sanitarium into south Florida's soupy
heat.
[Byline: Martha Mendoza and Margie Mason]
--
Communicated by:
Michael P. Owen, Regulatory Microbiologist
U.S. FDA Pacific Regional Lab Northwest
<michael.owen@fda.hhs.gov>
[Multidrug-resistant TB or MDR-TB refers to tuberculosis that is
caused by a strain of _Mycobacterium tuberculosis_ resistant to 2 of
the most effective drugs used to treat TB, isoniazid (INH) and
rifampin. Extensively drug-resistant TB or XDR-TB refers to a
subgroup of MDR-TB caused strains that are additionally resistant to
any of the fluoroquinolone class of drugs (e.g., levofloxacin.
moxifloxacin, or gatifloxacin) and any of the 3 injectable drugs used
to treat tuberculosis (capreomycin, kanamycin and amikacin).
In 2003, 2 middle-class, HIV-negative, Italian women died of
tuberculosis that was caused by strains resistant to every
anti-tuberculosis drug (Migliori GB et al. First tuberculosis cases
in Italy resistant to all tested drugs. Eurosurveillance Weekly
Release 12: 5, 2007). The authors of the report attributed the
development of drug resistance in these patients to medical
mismanagement and inappropriate use of anti-tuberculosis therapy. WHO
referred to these cases as extremely drug-resistant tuberculosis or
XXDR-TB that was defined as TB due to strains resistant to all 1st
and 2nd line anti-TB drugs
(<http://euro.who.int/tuberculosis/publications/20071204_5> and
<http://www.aidsmap.com/en/news/CBA086E0-D64C-43A4-B9A5-D21C57B35E8D.asp>).
1st line anti-TB drugs are: INH, rifampin, pyrazinamide, ethambutol
and streptomycin; and 2nd line drugs are: amikacin, kanamycin,
capreomycin, viomycin, fluoroquinolones, ethionamide, cycloserine,
and para-aminosalicylic acid
(<http://www.ncbi.nlm.nih.gov/pubmed/15971391>). 3rd-line drugs
include the macrolides (such as clarithromycin), clofazimine (that
could have caused the reported discoloration of this patient's skin),
amoxicillin/clavulanic acid, linezolid, imipenem, high-dose
isoniazid, and several new investigational drugs.
Exactly how many 3rd-line anti-TB drugs to which the Peruvian
patient's TB strain was resistant and how many drugs were used in
combination to result in a clinical response and apparently in
sterilization of his sputum is not specified in the news release
above.
The Peruvian patient, who was reportedly visiting the USA to study
English, is fortunate that he likely did not have AIDS, for otherwise
he likely would not have survived TB, which is a major killer of
patients with AIDS. The patient will have to be followed for a period
of time after his course of anti-TB chemotherapy ended to evaluate
for relapse before the patient can be said to be actually "cured."
Standard definitions of "cure" have been designed for MDR-TB, but not
for XXDR-TB: "Sputum cultures should be performed monthly (a minimum
recommendation is every 2 months) during therapy"; "An MDR-TB patient
who has completed treatment according to country protocol and has
been consistently culture-negative (with at least 5 results) for the
final 12 months of treatment"; and "Patients should be followed for 2
years after the initial outcome is assigned to allow detection of
relapse and evaluate the accuracy of the definitions"
(<http://www.ncbi.nlm.nih.gov/pubmed/15971391>).
The Peruvian patient likely acquired XXDR-TB from another as yet
unidentified individual with contagious XXDR-TB; in other words he
has primary drug resistance, rather than secondary drug resistance
that was acquired as a consequence of emergence of drug-resistant
mutants during improper exposure to anti-TB drugs. Peru is said to
currently have a major problem with multidrug-resistant tuberculosis
(MDR-TB)
(<http://ajrccm.atsjournals.org/cgi/content/full/169/12/1336-a>),
although I am unaware of XXDR-TB having been reported in Peru.
The state of Florida can be located on a map of the USA at
<http://healthmap.org/promed?v=40,-97.6,4>. - Mod.ML]
[see also:
Tuberculosis, MDR - China 20090114.0151
2008
---
Tuberculosis, XDR - Austria ex Romania 20080803.2373
Tuberculosis, MDR, XDR - Peru 20080412.1337
Tuberculosis, XDR - Namibia 20080403.1231
Tuberculosis, XDR - UK (Scotland) ex Somalia 20080322.1094
Tuberculosis, MDR, XDR - Worldwide: WHO 20080228.0813
Tuberculosis, MDR - South Africa 20080208.0521
Tuberculosis, MDR - Papua New Guinea 20080206.0478
Tuberculosis, XDR - Botswana, South Africa 20080118.0222
2007
----
Tuberculosis, XDR, MDR: genome sequences 20071122.3780
Tuberculosis - Uganda (02): MDR, susp. RFI 20071004.3284
Tuberculosis - Uganda: deadly strain, RFI 20071002.3255
Tuberculosis, XDR - South Africa (11): fugitives 20071002.3251
Tuberculosis, XDR - South Africa (10): Western Cape 20070627.2071
Tuberculosis, XDR - worldwide (02) 20070623.2034
Tuberculosis, XDR - South Africa (09): Western Cape 20070604.1805
Tuberculosis, XDR, airplane exposure - multicountry (03) 20070601.1778
Tuberculosis, XDR, airplane exposure - multicountry (USA, France,
Canada, Czech Rep.) 20070529.1738
Tuberculosis, XDR - South Africa (08): Western Cape 20070425.1349
Tuberculosis, XDR, 2003-2006 - Europe (Germany, Italy) 20070403.1132
Tuberculosis, XDR - South Africa (07): Eastern Cape 20070326.1044
Tuberculosis, XDR, 1993-2006 - USA 20070322.1005
Tuberculosis, XDR - South Africa (06) 20070319.0959
Tuberculosis, XDR, 1991-2003 - Spain 20070302.0738
Tuberculosis, XDR - South Africa (05) 20070228.0717
Tuberculosis, XDR - South Africa (04) 20070220.0638
Tuberculosis, XDR - South Africa (03) 20070209.0504
Tuberculosis, XDR - worldwide 20070205.0456
Tuberculosis, XDR - South Africa (02) 20070128.0375
Tuberculosis, XDR - South Africa: interventions 20070126.0349]
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