||Acid-fast bacilli. Microorganisms that retain
certain applied stains after being rinsed with an acid solution.
Most acid-fast organisms detected in patient specimens are mycobacteria.
When viewed under the microscope using the Zhiel-Neelson staining
method, M. tuberculosis bacteria appear red on a blue
background. When AFB are seen on a stained smear of sputum or
other specimen, a diagnosis of TB disease should be suspected,
and the concentration of organisms per unit area of slide (the
smear grade) correlates with the degree of infectiousness. The
diagnosis of TB disease is usually not confirmed until a culture
is grown and M. tuberculosis is identified. A positive
nucleic acid amplification (NAA) test is useful as a confirmatory
|Agarose gel electrophoresis
|| A laboratory method used to separate molecules. IS6110-based
RFLP uses agarose gel electrophoresis to separate DNA fragments
|| Bacille Calmette Guérin. A BCG isolate is commonly used as
a control strain in spoligotyping assays.
|| An isolate of the Beijing strain of M. tuberculosis
is commonly used as a control strain in spoligotyping assays,
since it has an unusual octal designation: 00000000000371.
|| Contact between a source case and someone else that is not
prolonged and often that occurs in a nontraditional setting.
The common teaching that TB is not transmitted by casual contact
needs to be revised in light of genotyping studies that show
it occurs more commonly than was once thought.
|Chain of recent transmission
|| Patients with TB who have transmitted M. tuberculosis
among themselves recently. Genotyping provides additional information
to traditional epidemiologic links to define chains of recent
transmission, since patients who are involved in the same chain
of recent transmission will almost always have M. tuberculosis
isolates that have matching genotypes.
|| Clinical Laboratory Improvement Amendments. The CLIA program
is operated by the Department of Health and Human Services to
ensure quality laboratory testing.
|| A person who has shared the same air space with a person
who has infectious TB disease and is among those of highest
priority of triaged contacts based on historical, social, and
epidemiologic data to warrant investigation.
|| A genotyping cluster is two or more M. tuberculosis
isolates that share matching genotypes. An epidemiologic cluster
is two or more persons with TB who share known epidemiologic
links. See Cluster investigation, Epidemiologic cluster,
Genotyping cluster, epidemiologically confirmed genotyping cluster.
|| An investigation to identify epidemiologic links between
TB patients whose isolates have matching genotypes. A cluster
investigation may consist of reviewing information from medical
records and interviewing case managers and outreach workers.
It can also involve interviewing TB patients. The term has also
been used to describe an investigation of TB patients who share
epidemiologic links before genotyping results are known.
|| An investigation of persons who have come into contact with
a patient with infectious TB. The goals of a contact investigation
are to identify additional persons with active TB, to determine
if transmission occurred between the TB patient and the contacts,
and to identify person with latent TB infection who are candidates
|| Transmission of TB from a patient who resides in one TB program
jurisdiction to a person who lives in another TB program jurisdiction.
Since genotyping results are not automatically shared between
TB program jurisdictions, special attention needs to be paid
to this possibility.
|Drug susceptibility test
|| A laboratory test to determine if a M. tuberculosis
isolate is susceptible to a specific drug used to treat TB.
|| A laboratory approach that provides a description of the
genetic makeup of a M. tuberculosis complex isolate.
|| A strain of M. tuberculosis that has circulated in
a relatively closed population for many years. Patients who
are infected with endemic strains are often not involved in
the same chain of recent transmission (i.e., within the previous
2 years), even though the genotypes of the isolates from the
patients match. (See Braden 1997.)
|| Two or more persons with TB who share known epidemiologic
links. Many scientists use the term “cluster” to refer only
to isolates with matching genotypes, but the term “epidemiologic
cluster” has become common enough to include as a legitimate
|Epidemiologically confirmed genotyping cluster
|| Genotyping cluster that contains TB patients with known epidemiologic
|Epidemiologic (Epi) link
|| A characteristic that two TB patients share that explains
where and when TB could have been transmitted between them.
An epidemiologic link could be a location where the two persons
spent time together or a relationship that brought them together.
A known epidemiologic link is defined as either a) one of the
patients named the other as a contact during one of the patient’s
infectious period or b) the two patients were at the same place
at the same time during one of the patient’s infectious period.
A possible epidemiologic link is defined as either a) the two
patients spent time at the same place but the timing of when
they were there or the timing of the infectious period was not
definite enough to meet the criteria for a known epidemiologic
link; OR b) the two patients lived in the same neighborhood
around the same period of time; OR c) the two patients worked
in or were at the same geographic area around the same period
of time and shared social or behavioral traits that increased
the chances of transmission.
|| A group of people who shared the same air space with a TB
patient during the patient’s infectious period. An outbreak
investigation focuses on defining the exposed cohort for infectious
TB patients in order to identify contacts that need to be screened
for TB and latent TB infection.
|| Cultures or reports of cultures of M. tuberculosis
that are not accurate. False-positive cultures occur when M.
tuberculosis bacteria from one specimen, instrument, or
culture inadvertently contaminate another specimen or culture
or when clerical errors occur and specimens are mislabeled or
misreported. Clinical equipment (e.g., bronchoscopes, sputum
collection booths, and ultrasonic nebulizers), if inadequately
cleaned, can become contaminated and be the source of false-positive
cultures. Cross-contamination can occur in the laboratory during
batch processing, pipetting, transfer of bacilli from a broth-culture
system, work in a faulty exhaust hood, or species-identification
|| Refers to TB genotyping using IS6110-based RFLP analysis.
|| Synonym for Genotyping cluster.
|| The designation that results from one or more of the three
genotyping techniques used for M. tuberculosis: spoligotyping,
MIRU analysis, and IS6110-based RFLP.
|| A group of isolates that share the same genotyping pattern.
This term is also applied to the TB patients who produced the
isolates with the same pattern. The genotyping laboratories
will report a PCR cluster designation for isolates with spoligotypes
and MIRU types that match other isolates from the same TB program.
The laboratories will report a PCR/RFLP cluster designation
for isolates in the same PCR cluster that also have the same
|| Two or more M. tuberculosis isolates that share the
|| Also referred to as DNA genotyping. A laboratory approach
used to determine if M. tuberculosis isolates are genetically
|| The H37Rv M. tuberculosis strain is commonly used
as a control strain in laboratory assays.
|| A condition in which the immune system is not functioning
normally. According to some style experts, immunocompromised
is the broader term, and immunosuppression is restricted
to states with iatrogenic causes, including causes that result
from therapy for another condition. Immunocompromised persons
are at greatly increased risk for progressing to TB disease
after infection with M. tuberculosis. Immunocompromised
conditions also make TB disease more difficult to diagnosis,
increasing the likelihood of a false-negative result for a test
for M. tuberculosis (e.g., TST).
|| The first TB patient identified in cluster. The index case
is not necessarily the source case.
|| The time period during which a person with TB disease is
considered infectious and capable of transmitting M. tuberculosis
to persons who share the same air space. See Chapter 4,
Combining Genotyping and Epidemiologic Data to Improve
Our Understanding of Tuberculosis Transmission, for details.
|| Insertion sequence 6110 (read “I- S-sixty-one-ten”)
is a genetic marker apparently unique to members of the M.
tuberculosis complex. IS6110-based restriction fragment
length polymorphism (RFLP) analysis was the first widely used
method for genotyping M. tuberculosis isolates.
|| The geographic extent of a TB program’s coverage. The jurisdiction
of a county health department is that county.
|| Latent tuberculosis infection.
|| A family of isolates of M. tuberculosis found commonly
among immigrants from Manila. The spoligotype and MIRU genotype
of Manila strain isolates are similar, yet in most cases, patients
infected with the Manila strain do not represent recent transmission.
IS6110-based RFLP is helpful in distinguishing between
Manila strain isolates within a PCR cluster.
|| Two or more M. tuberculosis isolates that share the
same genotype. See Chapter 4, Combining Genotyping
and Epidemiologic Data to Improve Our Understanding of Tuberculosis
Transmission, for more information.
|MDR and MDR TB
|| Multidrug-resistant and multidrug-resistant tuberculosis.
M. tuberculosis strains that are resistant to at least
isoniazid (INH) and rifampin.
|| Mycobacterial interspersed repetitive unit analysis (read
“MIR-ooh”). MIRU is a PCR-based genotyping assay. The CDC genotyping
program requires the regional genotyping laboratories to perform
MIRU analysis on every isolate submitted. See Chapter 3,
CDC Tuberculosis Genotyping Laboratory Procedures,
for more information.
|M. tuberculosis complex
|| Often abbreviated MTC, a group of closely related
mycobacterial species that can cause LTBI and TB disease (i.e.,
M. tuberculosis, M. bovis, M. africanum, M. canetti, M. microti,
and the BCG strain). Most TB in the United States is caused
by M. tuberculosis.
An isolate that has a unique genotype (i.e., a genotype
pattern that does not match the pattern of any other isolate
in a TB program’s database).
|| A setting where TB transmission took place that is not considered
a traditional transmission setting, such as the home or workplace.
Common nontraditional transmission settings identified during
cluster investigations have included bars and social clubs,
churches/temples, and drug/crack houses.
|| Organisms that can no longer be grown in culture. Genotyping
techniques that are based on the PCR test can by performed on
nonviable cultures. IS6110-based RFLP, on the other hand,
requires viable cultures that can be grown until they provide
|| National Tuberculosis Controllers Association.
|| National Tuberculosis Genotyping and Surveillance Network.
This network was established by CDC in 1996 to assess the utility
of molecular genotyping for improving tuberculosis prevention
and control. The NTGSN study included seven laboratories and
seven sentinel surveillance sites in the United States. Sentinel
surveillance sites included the states of Arkansas, Maryland,
Massachusetts, Michigan, and New Jersey and six counties in
California (Alameda, Contra Costa, Marin, San Mateo, Santa Clara,
and Solano); and four counties in Texas (Dallas, Tarrant, Cameron,
|| To simplify the recording of the results of spoligotyping,
the results are given as an octal representation. The octal
designation uses base 8, which contains the numbers 0--7. Any
spoligotyping banding pattern can be converted to an octal designation,
and any octal designation can be converted back to give the
original hybridization pattern. See Chapter 3, CDC Tuberculosis
Genotyping Laboratory Procedures, for details.
|| An increase in the number of TB cases in time and space over
that which is expected. See Chapter 6, Applying
Genotyping Results to Tuberculosis Control Practices, for
|| An investigation of an outbreak with the goals of a) identifying
and treating all cases of active TB so that transmission stops
and b) identifying all cases of LTBI that would benefit from
treatment and assuring that it is completed so the outbreak
does not continue in the future.
|| Polymerase chain reaction. The CDC genotyping program uses
two PCR-based techniques --- spoligotyping and MIRU analysis.
Only a small amount of culture is needed for PCR-based genotyping,
and the PCR test can be completed in 1day (because the PCR tests
are batched, the actual turn-around time from receipt of a specimen
to reporting the results can be longer).
|PCR cluster designation
|| The genotyping laboratories will assign a PCR cluster designation
to M. tuberculosis isolates that have matching genotypes
by the two PCR tests, spoligotyping and MIRU analysis. See Chapter
4, Combining Genotyping and Epidemiologic Data
to Improve Our Understanding of Tuberculosis Transmission,
|PCR/RFLP cluster designation
|| The genotyping laboratories will assign a PCR/RFLP cluster
designation to M. tuberculosis isolates that belong to
the same PCR cluster and are demonstrated to have the same RFLP
pattern. See Chapter 3, CDC Tuberculosis Genotyping
Laboratory Procedures, for details.
|| The transmission of TB that has occurred in the recent past,
as opposed to reactivation of a latent TB infection. Although
the precise time period that distinguishes TB that resulted
from “recent” transmission and TB that resulted from reactivation
of a latent infection is not well defined, “recent” transmission
is often considered to be within the last 2 years.
|Reinfection vs. relapse
|| A case of relapsed TB represents a worsening of an infection
after a period of improvement and is caused by the same strain
of M. tuberculosis. TB that represents a reinfection
is caused by a second infection with a strain that is different
from the strain that caused the initial infection. Genotyping
the initial and the subsequent M. tuberculosis isolate
can distinguish these two possibilities.
|| Restriction fragment length polymorphism. A genotyping technique
based on measuring the number and length of specific DNA fragments
that are cut using specific restriction enzymes. The RFLP technique
used to genotype M. tuberculosis is based on the IS6110
|| Report of a Verified Case of TB. National surveillance data
on patients with tuberculosis is recorded onto this report form.
|| The process of submitting only selected isolates for genotyping.
Because of the cost of submitting all isolates for genotyping
(i.e., “universal genotyping”), some programs may initially
have to select only high-priority isolates to be submitted for
genotyping. See Chapter 5, Developing a Tuberculosis Genotyping
Program, for more information.
|| A patient with infectious TB who is thought to be the source
of another patient’s TB infection. Also referred to as the source
|| Spacer oligonucleotide genotyping. A genotyping technique
based on spacer sequences found in the direct repeat region
in the M. tuberculosis chromosome. See Chapter 3, CDC
Tuberculosis Genotyping Laboratory Procedures, for more
|| Usual or suspected settings for TB transmission, such as
the home or workplace. See also Nontraditional setting.
|| Tuberculin skin test.
|| A genotype designation that does not match that of any other
isolate in a TB program’s database.
|| The policy of submitting all M. tuberculosis isolates
for genotyping. See Chapter 5, Developing a Tuberculosis
Genotyping Program, for more information.
|| Variable number tandem repeat analysis. VNTR is a type of
MIRU analysis. See also MIRU.