A tiny filter could have a big impact around the
world in the fight against tuberculosis. Using the traditional microscope-based
diagnosis method as a starting point, a University of Florida lung disease
specialist and colleagues in Brazil have devised a way to detect more cases of
the bacterial infection.
"We're hopeful that
this more sensitive method, which is both simple and inexpensive, will
improve diagnosis in
patients," said lead researcher Kevin Fennelly, M.D., M.P.H., an associate
professor in the UF College of Medicine's department of medicine and
Southeastern Tuberculosis Center,
and the UF Emerging Pathogens Institute.
The new technique, which
involves vacuum filtering
a sputum sample treated with household bleach and other simple chemicals
through a small filter, could dramatically improve TB diagnoses globally,
particularly in settings where the disease is common and resources are limited.
It is especially useful when the presence of only a small number of bacteria in
the test sample makes it hard to detect TB. The researchers are refining the
technique in hopes of developing a cost-effective product that can be used
globally.
Funded by the World Health
Organization and the Núcleo de Doenças Infecciosas infectious disease
institute in Brazil, the study appears online and in an upcoming print edition
of the Journal of Clinical Microbiology.
TB is a treatable disease
caused by a microbe called Myocardium tuberculosis. It most often affects the
lungs, but can also target organs such as the brain, spine and kidneys.
Symptoms of active disease include a chronic cough, sputum production and
coughing up blood. TB spreads from person to person through the air.
Once the leading cause of
death in the U.S., TB has been largely under control in Western nations. Still,
more than 11,000 U.S. cases were reported in 2010, the latest year for which
there is comprehensive data. That year, almost 9 million people around the
world were diagnosed with TB and almost 1.5 million died from it. TB causes
more deaths than any other bacterial infection and
is the most common killer of people living with HIV.
"TB is still a
tremendously important disease worldwide and control efforts are greatly
hindered by lack of simple, inexpensive diagnostics that could be used at the
point of care," said Elizabeth Talbot, M.D., a Dartmouth College
infectious diseases and TB diagnostics expert who was not involved in the UF
research. "What Dr. Fennelly has done is capitalize on existing
infrastructure of microscopy to try to improve performance of that prevalent
diagnostic tool."
The most widely used way
to confirm TB infection is to use a microscope to
identify and count disease-causing bacteria in sputum smeared onto a glass
slide. This so-called direct-smear method also helps health professionals
figure out how likely people are to pass on the disease, what treatment
decisions should be made, and how well patients are responding to treatment.
Although the method has been in continuous use for more than a century, it can
be unreliable, catching cases only about half of the time, on average.
Part of the problem is
that sometimes sputum samples don't contain many bacteria, making it hard to
detect TB. Concentrating bacteria onto a small area could help improve
detection accuracy, and although previous efforts have led to improvements,
they tend to require expensive equipment or technical know-how. In some cases,
gains were offset by loss of sample or safety concerns. So the quest for a
low-cost, simple, effective method led back to the trusty microscope.
In the early 1980s
researchers vacuum-filtered sputum samples to trap TB bacteria onto
quarter-sized filters that were then viewed under a microscope. But the filters
hung over the sides of standard microscope slides, posing a health hazard and
preventing proper inspection. So Fennelly and his team decided to try
smaller-than-a-dime filters that fit neatly onto microscope slides and that
concentrated the bacteria even more.
Among 314 patients in
Brazil suspected as having TB, but not yet in treatment, the small-filter
method detected 89 percent of cases, compared with 60 percent detection when
samples were concentrated by the currently used method of rapid spinning, and
56 percent detection when sputum smears were looked at directly under the
microscope.
Furthermore, the
small-filter method identified almost three-quarters of TB-positive cases that
had been incorrectly reported as negative based on the traditional technique.
Fennelly and
collaborators are now teaming with the humanitarian organization Médecins Sans
Frontières, translated as "Doctors Without Borders," to test the
method in western Uganda, where many people have both TB and HIV. They're
comparing it again with the traditional direct-smear method and with a
sophisticated DNA-based test that can also detect whether bacteria are drug
resistant.
Both types of technique
have their place — high-tech tools would be most feasible in referral centers,
but on the front lines, the small-filter microscope method can perform an
invaluable service, the researchers say.
"A point-of-care
dipstick that can say yes or no is the Holy Grail, but we're a long way from
there," Fennelly said. "'Microscope' has become a dirty word in the
TB diagnostics world — but almost every clinical laboratory in the world has
one."
Journal reference: Journal
of Clinical Microbiology
Provided by University
of Florida
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