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5
Diagnosis of Drug-Resistant TB
Key Messages
• apid diagnostic methods would permit more immediate initiation
R
of effective treatment, thus reducing the amount of time that MDR
TB patients are infective.
• olecular-genetic methods, including gel-based biological micro-
M
chips, can reduce diagnostic intervals to as little as 1−2 days.
• aboratory information management systems allow use of diag-
L
nostic results to maximum advantage and monitoring of treatment
results.
• he effectiveness of these laboratory information management
T
systems would be enhanced if information could be shared in
common public health databases even if the information manage-
ment systems were based in different technology and software
platforms.
Presentations on the diagnosis of drug-resistant TB addressed rapid
diagnostic methods, the use of biochip technology, and the need for
improved laboratory capacity.
49
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50 DRUG-RESISTANT TUBERCULOSIS IN RUSSIA
RAPID DIAGNOSTIC METHODS1
CTRI of the Russian Academy of Medical Sciences uses both conven-
tional and newer, rapid methods of mycobacteria identification (see Box
5-1 for an overview of current TB diagnostic methods). The conventional
methods used are fluorescent microscopy and culture, which can require up
to 10 weeks for culturing and an additional 4 weeks for drug susceptibility
testing. During this time, physicians and patients must wait to determine
how to treat the patient’s TB, and this delay provides an opportunity for
the disease to spread. To shorten this time, CTRI has been using commercial
products that rely on culturing and on molecular-genetic methods. These
products can determine which strains are resistant or sensitive to specific
drugs through colorimetric methods, with automatic detection and no use
of test tubes, and reduce the time required to obtain drug susceptibility
results to 6−13 days.
The molecular-genetic methods rely on detection of mutations in the
DNA of M.tb. that convey drug resistance. One such method uses biochips
developed in Russia (see the next section). It involves the extraction of
M.tb. DNA, two-stage polymerase chain reaction (PCR), hybridization with
amplicons labeled with fluorescent marks on the biochip, and detection of
results using an analyzer with subsequent computer processing.
A comparison of biochip and culture data showed a concordance of 95
percent for rifampicin resistance, 88.5 percent for isoniazid resistance, and
87 percent for fluoroquinolone resistance. These are reassuring numbers,
said Larionova, since not all mutations responsible for resistance are found
using biochips.
Other molecular-genetic methods used to detect drug resistance involve
DNA-strip or related technologies. They rely on DNA extraction, ampli-
fication by PCR, hybridization on strips, and visualization and estimation
of results. These methods are highly safe, easy to use, and cost-effective.
Results are available within 1−2 days and can be obtained from either solid
or liquid media. A comparison of results from biochips and DNA strips
demonstrated full concordance.
The above technologies allow for the detection of MDR and XDR
TB during a patient’s examination and the administration of adequate
chemotherapy regimens to shorten the sputum conversion period, improve
treatment outcomes, and prevent the spread of disease. Experience at CTRI
indicates that 64 percent of new MDR TB cases convert after 2 months of
treatment and 87 percent after 6 months of treatment.
New methods are also being used to diagnose infection with nontuber-
1 This
section is based on the presentation of Elena Larionova, Central TB Research Institute,
Russian Academy of Medical Sciences.
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51
DIAGNOSIS OF DRUG-RESISTANT TB
BOX 5-1
Some Diagnostic Methods Currently in Use for TBa
Microscopy smear. Experience has shown that microscopy can de-
tect TB, but the sensitivity is variable and can be very low.
Culture/phage based. Culturing bacteria takes longer than a smear
test but is more sensitive. Smear-negative but culture-positive tests allow
for earlier treatment and a reduction in transmission.
Molecular, bacteria based (e.g., PCR). Many reports on the per-
formance of PCR in diagnosing TB have appeared since 1985. Positive
results from these types of tests do not guarantee live bacteria, and
repeatability issues have arisen. Specificity and sensitivity depend on
the kind of sample, the kind of test, and the manufacturer. PCR may not
be much better than culture for “difficult samples” such as pleural fluid or
urine, and the sample preparation method can generate problems. Ac-
cording to Paul van Helden, Stellenbosch University, PCR also can be
very expensive unless a cartridge-based test is used, and even the cost
of a cartridge-based PCR test, at about US$40 or more per person, is
unaffordable in the developing world. PCR has a number of applications
beyond the diagnosis of TB. Scientists and clinicians can use it as a
basic research tool, to assign isolates of M.tb. to a particular strain, and
to obtain drug resistance information. Furthermore, many applications
can be automated to reduce costs. In the future, for example, multiple
fluorescent probes might generate considerable information simultane-
ously, said van Helden.
DNA based. As mentioned in Chapter 2 (Box 2-1), since the work-
shop was held in Moscow, a new, fully automated DNA test (Xpert MTB/
RIF) for TB has been validated and subsequently recommended by the
WHO for broad implementation as the initial diagnostic for individuals
suspected of having MDR TB or HIV−TB coinfection. The test simultane-
ously detects TB and rifampicin drug resistance (a reliable indicator for
MDR TB) in sputum. WHO reports that FIND has negotiated a reduced
price for 116 low- and middle-income countries (including South Africa,
Russia, India, and China) of US$16.86 per test cartridge. The test pro-
vides results in 100 minutes, allowing proper treatment to begin imme-
diately (WHO, 2010d).
SOURCE: IOM, 2011.
aThe information provided in this box was originally presented by Paul van Helden, Stellen-
bosch University, and summarized in the IOM Drug Forum’s second workshop on the subject
of drug-resistant TB held in 2010 in Pretoria, South Africa (IOM, 2011).
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52 DRUG-RESISTANT TUBERCULOSIS IN RUSSIA
BOX 5-2
New Methods for Species Identification of
Nontuberculosis Mycobacteriaa
Infection by nontuberculosis mycobacteria is the cause of mycobac-
teriosis, a frequent opportunistic infection in patients with AIDS. New
liquid culture-based automatic systems and molecular-genetic systems
have made it possible to identify both NTM infection and the species of
NTM involved.
The gold standard for NTM detection today is sequencing of the bac-
terial genome, but not all laboratories are equipped with DNA sequenc-
ers. Restriction fragment length polymorphism analysis using PCR is
much more commonly employed, and several commercially available
test systems exist.
Mass spectrometry is another technology used to identify NTM spe-
cies. Smirnova is involved in an effort to identify NTM strains by direct
protein profiling using mass spectra for ribosomal proteins. She and her
colleagues have collected 35 strains of NTM and have characterized
each using several methods, including microbiological, PCR-based, and
mass spectrographic techniques. Accumulation of mass spectrometry
data for conserved proteins will allow for the creation of a database that
can be used for species identification.
Little information about mycobacteriosis is available in Russia, said
Smirnova, and species identification of mycobacterial cultures is rarely
performed in bacteriological laboratories. In addition, no molecular-
genetic systems are available for the quick and inexpensive identification
of NTM. Spectrographic determination may offer a way to fill this gap.
culosis mycobacteria (NTM) and to identify the species of NTM involved.
Box 5-2 summarizes a presentation on this subject.
In the discussion period, Maria Y. Giovanni of the National Institute
of Allergy and Infectious Diseases (NIAID), U.S. National Institutes of
Health (NIH), noted that NIAID supports a comprehensive program of
research and development in diagnostics. She also suggested that all diag-
nostics still need to be faster, easier to use, and less expensive. Kathleen
Eisenach, University of Arkansas, pointed out that the Institute of Tropical
Medicine in Antwerp does quality control testing for drug susceptibility
tests worldwide. A panel of isolates, including MDR TB strains, is circu-
lated to laboratories once or twice a year, which provides an opportunity
for proficiency testing. “These coordinated efforts help us have confidence
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DIAGNOSIS OF DRUG-RESISTANT TB
Many other questions surround the diagnosis and treatment of NTM
infection. How can drug susceptibility testing for NTM be performed?
Who should treat patients with mycobacteriosis, where should they be
treated, and how, given that mycobacteriosis is not TB? Physicians are
insufficiently educated in the diagnosis and treatment of patients with
mycobacteriosis, and delays in diagnosis and treatment can lead to
severe and progressing disease.
In the discussion period, Carlos Pérez-Vélez of the National Jewish
Hospital, Denver, Colorado, commented on the treatment of mycobac-
teriosis at the hospital, which typically has 10 such patients who have
been referred from around the world. An interdisciplinary team of pul-
monologists and infectious disease specialists manages these patients,
who usually require prolonged courses of multiple antibiotics. Success
for these patients depends on susceptibility testing, the management
of adverse effects from antibiotics, and pharmacokinetic studies of indi-
vidual patients. “The same doses in people of similar weight [and other
characteristics] can vary, so sub-therapeutic dosing is really a problem
in nontuberculous mycobacterial infections,” said Pérez-Vélez. Many pa-
tients with MDR TB actually have an NTM infection that is resistant to
isoniazid and rifampin, and some people have a mixed infection, he
noted. These mixed infections can be very difficult to diagnose, since one
bacterium can outgrow and overshadow another.
aThe information presented in this box is based on the presentation of Tatiana Smirnova,
Central TB Research Institute, Russian Academy of Medical Sciences.
in the drug susceptibility testing that is being performed at all levels in all
countries,” she said.
Several participants discussed the prospects for diagnostics that use
sputum or some other sample and do not involve culturing. Coetzee noted
that several technologies do not require culturing and have produced good
results. However, they do not work as well in HIV-infected patients, who
have a lower smear-positive rate than other TB patients.
Several participants compared the cost of diagnostics with the cost of
treatment. Given the expense of second-line drugs, even quite expensive
diagnostics may be cost-effective. “A day of capreomycin, even at discount
rates, costs $3 to $5,” said Cassell. Therefore, she suggested, it makes no
sense to wait for a $1 test. Accurate diagnostics also could obviate the need
for expensive follow-up tests.
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54 DRUG-RESISTANT TUBERCULOSIS IN RUSSIA
Keshavjee pointed out that airline security systems now rely on mass
spectrometers to detect bomb-making chemicals within a few seconds. In
an ideal world, a TB diagnostic would produce results instantly so that the
proper treatment could be initiated at the point of care. Even if diagnostic
technologies are not perfect, they can suggest a treatment at the point of
care, and that treatment can be modified once more definitive results are
available.
BIOCHIP TECHNOLOGY FOR TB DIAGNOSIS2
Gel-based biological microchips were developed by Andrei Mirzabekov
at the Engelhardt Institute of Molecular Biology in the early 1980s, and
much progress has been made on their further development since then, said
Zimenkov. Today, biochips are based on three-dimensional gel pads on a
plastic surface rather than two-dimensional glass surfaces, which increases
the sensitivity of analysis and leads to excellent discrimination levels. Point
mutations are detected by DNA hybridization on the biochip, with fluores-
cence intensities being compared to determine whether tested DNA bears
a particular mutation. Software is user-friendly for medical personnel, and
the biochip analyzer has been certified in clinical trials.
In 2001 the Institute of Molecular Biology received support from the
International Science and Technology Center (ISTC) to study the applica-
tion of biochips in TB diagnostics for fast discrimination and strain typing
of MDR TB in Russia. Biochips were developed to detect mutations leading
to resistance to rifampicin and isoniazid. The chips were able to identify
more than 95 percent of rifampicin-resistant TB strains and more than 80
percent of isoniazid-resistant strains. Since being certified in 2004, the bio-
chip has been used in more than 10,000 analyses.
The use of biochips has had a major impact on treatment. When bio-
chips were used to determine second-line treatments in MDR TB cases,
healing, or bacterial conversion, was approximately twice as rapid as when
classical methods were used, according to Zimenkov (Kuzmin et al., 2006).
Similar results were obtained in a comparison of three groups: one con-
sisting of people resistant to one or two drugs who received the standard
treatment, one consisting of MDR TB patients who received the standard
treatment, and a third treated after biochip analysis (Morozova, 2008).
A more recently developed biochip detects mutations involved in resis-
tance to fluoroquinolones in about 80 percent of strains. Thus far it has
been used in more than 3,000 analyses in Russia and other countries. New
2 Thissection is based on the presentation of Danila Zimenkov, Engelhardt Institute of
Molecular Biology.
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DIAGNOSIS OF DRUG-RESISTANT TB
chips being developed detect additional mutations involved in fluoroqui-
nolone resistance.
Biochips also are being used to perform automated analyses of repeated
units in the DNA of M.tb., allowing different strains to be distinguished.
For example, the technology can distinguish bovis strains from Beijing
strains in about a day. The technology can now distinguish among more
than 100 strains of the bacterium, making it possible to determine the
extent to which strains are mixed in patients. This technology is being
extended to produce a biochip for mycobacteria differentiation.
In the discussion period, several workshop participants expressed inter-
est in the biochip, which was developed in part through a partnership with
Argonne Laboratory in the United States. Jeffrey Drazen, New England
Journal of Medicine, urged that quantitative research techniques be used
to study the biochip to determine its sensitivity and specificity relative to
standard diagnostic techniques. Drazen said that this type of information
would move the field from descriptive to quantitative research and would
be a positive step forward in terms of the scientific development of diag-
nostic techniques.
NEED FOR IMPROVED LABORATORY CAPACITY3
WHO’s Global Laboratory Initiative (GLI) has identified the need for
an urgent and massive scale-up of TB laboratory services. According to
the GLI, “The global lack of TB laboratory capacity constitutes a global
crisis, requiring a paradigm shift in providing laboratory policy guidance,
quality assurance and knowledge creation within a global and integrated
laboratory network.” Some of the challenges and successes of improving
laboratory diagnostic capacity are illustrated in Box 5-3.
Several critical issues surround global laboratory capacity, Nordenberg
said:
• L
aboratory capacity is desperately insufficient.
• L
aboratory capacity-building efforts rarely consider data and infor-
mation management.
• L
aboratory programs are focused on specimens and therefore have
information system requirements very different from those of clini-
cal or public health programs.
• E
merging diagnostics can change surveillance methods or the sen-
sitivity and specificity of both TB and drug-resistant TB testing,
3 This section is based on the presentation of Dale Nordenberg, Novasano Health and
Science.
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56 DRUG-RESISTANT TUBERCULOSIS IN RUSSIA
which in turn affects surveillance trend estimates and outbreak
control.
• T
here is a critical need to integrate the information systems of
laboratories, clinics, and public health programs.
• T
here is a critical need as well for “operations” systems to track
such activities as infection control programs and therapeutic supply
chains.
BOX 5-3
Diagnostics and Laboratory Infrastructure in South Africaa
Dr. Coetzee discussed South Africa’s latest efforts to organize labo-
ratory services for the effective diagnosis of drug-resistant TB. In South
Africa, simultaneous infection with HIV and TB has created a widening
gap between smear positivity and TB cases. As a result, smear micros-
copy is rapidly failing as a diagnostic tool and will soon become unusable,
Coetzee said, emphasizing that new diagnostics are desperately needed
to combat drug-resistant TB. In 2006 WHO held a meeting in South Af-
rica that generated a recommendation to develop and implement rapid
diagnostics throughout the country. In response, South Africa invested
heavily in line probe assays (LPAs).b Currently, line probes are running
in 15 laboratories, and they will be available in 10 more before the end
of 2010. However, this scaling up of LPA capacity is an extremely difficult
task. A significant challenge is the country’s workforce constraints, in
particular the small number of molecular biologists. The probes also were
placed in laboratories with good ventilation and working environments,
and such facilities are among the top few percent of African laboratories,
said Coetzee.
The performance of the implemented line probes has been high. How-
ever, the reading of the line probes had to be standardized. “We found
inter-observer errors in PhDs, so you can imagine what the rate would
have been in technicians,” said Coetzee. The line probes are scanned
and interfaced with the laboratory information system, which has pro-
duced standardized results.
The National Health Laboratory Service has about 350 laboratories,
and all of the public-sector laboratories have been consolidated into one
organization. This consolidation has enormous benefits for surveillance.
The development of an algorithm for the early detection of MDR TB was
a politically challenging process, Coetzee said. In the end, however, a
policy was established that a line probe will be administered to every new
smear-positive patient. If a patient is smear negative and culture positive,
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DIAGNOSIS OF DRUG-RESISTANT TB
The challenge, said Nordenberg, is that these issues apply not just
to one or two but to thousands of laboratories. To stop the spread of
TB globally, the world needs rapid, accurate diagnostics, particularly in
resource-poor settings. Also needed are drugs that will shorten treatment,
be effective against both susceptible and resistant strains, be compatible
with antiretroviral therapies, and improve the treatment of latent infection;
a vaccine that is safe and effective for children, adolescents, and adults,
the culture will undergo a line probe. This is an expensive process, but
less so than first-line drug susceptibility testing.
The infrastructure in much of South Africa is rural, with scattered
electricity and water supplies. However, cell phone reception is often
available. The country has begun using cell phone printers, through
which messages can be exchanged. With the rollout of the line probes,
TB facilities throughout the country began using a new form that makes it
possible to follow patients longitudinally through the system and monitor
their adherence to the TB control program. Information from the forms
is migrated to a central data warehouse in Johannesburg to produce a
single consistent view of the data. Information includes all demographic
data, all test results, all drug susceptibility test results, and billing infor-
mation. The new system is still being piloted, but Coetzee said the hope
is that it will improve adherence to policy.
Making the transition from specimen-based to patient-based data
has been difficult. Demographic information is often inadequate or inac-
curate. Data security and the user interface required considerable work.
Some of the data contained in approximately 12 million records had to
be checked visually.
The system also is being used for other infectious diseases in South
Africa, such as cholera and meningitis. Notification of an outbreak is
automatic through web-based portals. Reports can be generated by
province, by district, by subdistrict, or by clinic. South Africa is now en-
hancing its reporting for national health programs focused on HIV, TB,
cervical cancer, and sexually transmitted diseases. It also is working
to improve the spatial reporting of infectious diseases to assist various
health authorities.
aThe information in this box is based on the presentation of Dr. Coetzee.
bLine probe assay technology involves the isolation of DNA from sputum specimens for the
rapid detection of MDR TB.
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58 DRUG-RESISTANT TUBERCULOSIS IN RUSSIA
including people with HIV; and efficient and sustainable information supply
chains (discussed below).
The New Diagnostics Working Group of the STOP TB Partnership has
identified several critical attributes of TB diagnostics (WHO, 2009), finding
that such diagnostics should:
• s
implify and improve the detection of TB, including smear-negative,
extrapulmonary, and childhood TB, through increased sensitivity
and specificity and improved accessibility;
• o
ffer simple, accurate, safe, and inexpensive tests that can be per-
formed at the point-of-care level of the health care system and
produce same-day results;
• e
nable more effective monitoring of TB treatment for both latent
and active cases;
• r
apidly identify resistance to both first- and second-line TB drugs;
and
• r
eliably identify latent TB infection and determine the risk of pro-
gression to active disease, enabling the rational use of preventive
therapy.
Nordenberg suggested that information should itself be seen as an
intervention. The supply chain needs to get the right therapeutics to the
right patient. If a diagnosis is not used to drive treatment, a major oppor-
tunity is being missed. If cases are identified earlier, less resistance will
develop, patients will be less costly to treat, and fewer people will spread
the infection. Thus, the return on investing in information infrastructure
is very high. “Without that investment, all the investment in diagnostics is
compromised,” said Nordenberg.
The data produced by diagnostics can have a major impact on pub-
lic health, but they need to be collected, managed, and shared. Doing so
means moving across what Nordenberg called the “information chasm”
from laboratories to epidemiological and public health impact. Crossing
that chasm requires laboratory information management systems. Such a
system is a tool that supports the work of laboratories as opposed to that of
clinicians or health epidemiologists. A laboratory information management
system needs to perform a diverse set of functions—test requisition, test
receipt documentation, sample management, testing and validation, report
distribution, report receipt documentation, test scheduling, sample collec-
tion, chain of custody, reagent management, quality assurance, and others.
These functions are not in the domain of a clinician or epidemiologist. With
influenza, for example, various types of tests can be performed on a given
specimen. A laboratory information management system has to document
and be the repository of results from this complex analytic process.
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DIAGNOSIS OF DRUG-RESISTANT TB
About 80 percent of the 50 public health laboratories across the United
States have a laboratory information management system, after about 7
years of implementation efforts. Each state is implementing its own system,
while approximately five to seven different primary systems cover the 50
states. The laboratories perceive that they have differing needs with regard
to public health priorities, bench methodologies, and technologies. This
is also the case internationally; some countries in Africa, for example, are
implementing two or three different systems, even within the same city.
With the emergence of new technologies and new diagnostics, more-
over, local laboratories are conducting more of their analyses locally and
sending fewer specimens to regional or national laboratories for analysis.
As a result, local laboratories are starting to build their own data-sharing
networks. These networks need to be integrated with clinical, public health,
and other research activities. They also need to be able to handle not just
TB but also other infectious diseases. A public health laboratory is typically
responsible for a broad spectrum of programs, and a laboratory informa-
tion management system needs to support that mission. Nordenberg used
influenza as an example. More than 60 tests are used to describe and
manage an influenza epidemic. To facilitate data exchange, the national
laboratory community has made more than 500 specific data-related coding
decisions. Nordenberg emphasized the importance of being able to share
diagnostic data, which requires such collaboration.
Even though laboratories are working with different technology
platforms, they are identifying common data that they will share, so the
information kernel is standard. This kernel, derived from a description
harmonized by a community, must adjust dynamically as new scientific
methodologies and technologies emerge. Even before the first version of a
product has been fully implemented, new versions can appear that overlap
with the previous versions. At any given time, multiple versions may be in
use. Only through ongoing collaboration can a systems approach produce
an alignment of vision, mission, and execution.
Nordenberg emphasized that a public health information supply chain
is not an abstract concept, but something that must be engineered through
a comprehensive, logistics-based approach. In particular, a disciplined
approach to data and information provisioning will enable measurement of
the quality and impact of the data, allowing performance to be improved.
A systems approach, in contrast to an ad hoc approach, can produce
several additional capabilities. A systems approach is scalable, so that it
can meet the need for robust information supply chains in thousands of
laboratories across the globe. It is intentionally designed to be dynamic so
that it can be optimized through continuous performance improvement.
And it provides the ability to integrate data across laboratories, clinical
programs, and public health programs. A systems approach transcends a
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60 DRUG-RESISTANT TUBERCULOSIS IN RUSSIA
vertical, single-disease approach and can support diverse health care priori-
ties and programs.
Nordenberg outlined additional important capabilities of a laboratory
information management system:
• i
t must be sustainable;
• i
t must be cost-effective;
• i
t must leverage and build local expertise;
• i
t must be driven by public health and science, not just by
technology;
• i
t must be governed by stakeholders; and
• i
t must provide a clear path to robust capability while accommo-
dating a diversity of baseline capacity.
An information supply chain is distinct from the other supply chains
required to manage a TB or MDR TB program, such as people, hard goods,
diagnostics, therapeutics, reagents, and so forth. Nordenberg noted that
information is often overlooked when laboratory capacity is being built. As
a result, systems are frequently developed in an ad hoc manner, and there
is a divide between the technology platform and the ability to get the data
where they are needed.
The components of an information supply chain are information prod-
ucts, a source of raw materials, human resources, and standard operating
procedures, each of which must be articulated with the others. Information
products are motivated by the questions that drive decision making, and all
supply chains must reflect a clear idea of the products they need to produce.
The sources of raw materials are the data systems that provide the data for
information products. Human resources are the staff that build and operate
the systems and develop the information products. Standard operating pro-
cedures are the processes used to manage the data to produce information.
“The information supply chain is a complex endeavor,” said Nordenberg.
“It’s much easier to buy a piece of technology, or buy a system, install it,
collect the data, and then hope you get out of it what you need. But usually
you are going to be disappointed.”
To realize the full benefits of information systems, the laboratory, clinic,
and public health entities in a given area need to work together. Nordenberg
illustrated this point: “If you can get a laboratory result in 2 days or in 3
weeks, but then it takes another week to get the result of that test to some-
body, that’s going to have serious costs in terms of delayed diagnosis and
increased spread.” Especially with TB, the cost of a broken information
supply chain can be calculated in both human and financial terms.
Nordenberg offered several recommendations regarding information
supply chains:
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DIAGNOSIS OF DRUG-RESISTANT TB
• C
ountry plans for information supply chains should be developed
to support TB and MDR TB control.
• L
aboratories should collaborate multinationally and sustainably to
develop shared best practices.
• P
lans should be developed to migrate laboratories at all levels of
information technology capability to the same target capability.
• A
tight linkage should exist between diagnostics development and
data activities.
• T
echnology adoption and information capability should be tracked
to guide programs.
• M
etrics related to time from specimen acquisition to diagnosis and
treatment should be developed and tracked.
• I
nformation plans should be assessed annually to respond to new
developments in such areas as diagnostics, drugs, and intervention
programs.
• H
IV and TB data systems should be integrated to support the man-
agement of coinfected patients.
• E
ducational programs should impart a clear understanding of the
specific needs of laboratories versus clinical and epidemiological
activities.
During the discussion of information systems, Coetzee, Nordenberg,
and Renzhong Li of China’s Center for Disease Control and Prevention
discussed the degree of integration between the clinical and laboratory sys-
tems in different countries. In South Africa, said Coetzee, the systems are
not integrated. Even large hospitals have systems that handle only admin-
istrative and not clinical data. A new patient management system is being
implemented for lower-level clinics, which will help integrate the treatment
of HIV infection and TB. Also, there are limited interfaces between hospital
management systems and patient management systems. Much HIV testing
is no longer done at laboratories but at the point of care, which means that
previously available surveillance data have been lost. In China, said Li, data
from patient care are available but not from the laboratory system.
A workshop participant asked how data from private practitioners
in many countries can be integrated in the same system, since the same
platform probably will not be used to communicate results. Nordenberg
observed that the same situation exists in the United States, where a wide
diversity of independently run systems exists in both the public and private
sectors. He reiterated that effort is focused on creating an information ker-
nel that is constant so the data can be shared even though the technologies
differ. He also noted that the web-based patient-level system in China is
remarkably successful, reaching thousands of different entities—from the
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62 DRUG-RESISTANT TUBERCULOSIS IN RUSSIA
county, to the prefecture, to the province, to the national level—across the
country.
A participant pointed out that the ideal situation is to get data from
laboratories to clinicians rapidly so that treatment can begin. In some
countries, this information flows via cell phone, although provisions must
be made to ensure privacy. Also, private practitioners and laboratories need
to be integrated into public systems.
Nordenberg responded that the most efficient way to scale up com-
munications is through web-based systems. Implementing thousands of
information systems across laboratories of varying capacity is difficult. But
the problem of connectivity can be and is being solved through web-based
communications. In the short term, cell phone infrastructures can suffice,
particularly if systems are set up using passwords to protect privacy, accord-
ing to Nordenberg. It is also important, he said, for laboratories to share
best practices. For example, if different diagnostics have differing sensitivity
and specificity, how does that affect estimates of incidence? How can data
be shared within or across countries? How are reporting forms designed?
A workshop participant asked whether the widely varying results of
drug susceptibility testing in China argue for the use of individualized rather
than standardized treatments for MDR TB. Nordenberg asked whether the
laboratory results are fed into the patient information system. Li responded
that the patient data are referred to the TB dispensary. Nordenberg also
pointed out that, despite the excellent patient information system, the lack
of an integrated laboratory system in China makes it difficult to look at
population trends in resistance. The challenge, he said, is to run a program
focused both on resistance patterns and on patients.
