| AFB |
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 test. |
| Agarose gel electrophoresis |
A laboratory method used to separate molecules. IS6110-based RFLP
uses agarose gel electrophoresis to separate DNA fragments by size. |
| BCG |
Bacille Calmette Guérin. A BCG isolate is commonly used as a control
strain in spoligotyping assays. |
| Beijing strain |
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. |
| Casual contact |
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. |
| CLIA |
Clinical Laboratory Improvement Amendments. The CLIA program is operated
by the Department of Health and Human Services to ensure quality laboratory
testing. |
| Close contact |
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.
|
| Cluster |
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. |
| Cluster investigation |
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. |
| Contact investigation |
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 for treatment. |
| Cross-jurisdiction transmission |
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. |
| DNA genotyping |
A laboratory approach that provides a description of the genetic makeup
of a M. tuberculosis complex isolate. |
| Endemic strain |
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.) |
| Epidemiologic cluster |
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 term. |
| Epidemiologically confirmed genotyping cluster |
Genotyping cluster that contains TB patients with known epidemiologic
links. |
| 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. |
| Exposed cohort |
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. |
| False-positive culture |
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 procedures. |
| Fingerprinting |
Refers to TB genotyping using IS6110-based RFLP analysis. |
| Genetic cluster |
Synonym for Genotyping cluster. |
| Genotype |
The designation that results from one or more of the three genotyping
techniques used for M. tuberculosis: spoligotyping, MIRU analysis,
and IS6110-based RFLP. |
| Genotyping cluster |
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
RFLP pattern. |
| Genotyping match |
Two or more M. tuberculosis isolates that share the same genotype. |
| Genotyping |
Also referred to as DNA genotyping. A laboratory approach used to determine
if M. tuberculosis isolates are genetically related. |
| H37Rv strain |
The H37Rv M. tuberculosis strain is commonly used as a control
strain in laboratory assays. |
| Immunocompromised |
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). |
| Index case |
The first TB patient identified in cluster. The index case is not necessarily
the source case. |
| Infectious period |
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. |
| IS6110 RFLP |
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. |
| Jurisdiction |
The geographic extent of a TB program’s coverage. The jurisdiction of
a county health department is that county. |
| LTBI |
Latent tuberculosis infection. |
| Manila strain |
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. |
| Matching genotypes |
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. |
| MIRU |
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. |
| Nonmatching genotype |
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). |
| Nontraditional setting |
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. |
| Nonviable cultures |
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 sufficient material. |
| NTCA |
National Tuberculosis Controllers Association. |
| NTGSN |
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, and Hidalgo). |
| Octal designation |
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. |
| Outbreak |
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 more information. |
| Outbreak investigation |
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. |
| PCR |
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, for details. |
| 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. |
| Recent transmission |
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. |
| RFLP |
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 insertion sequence. |
| RVCT |
Report of a Verified Case of TB. National surveillance data on patients
with tuberculosis is recorded onto this report form. |
| Selective genotyping |
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. |
| Source patient |
A patient with infectious TB who is thought to be the source of another
patient’s TB infection. Also referred to as the source case. |
| Spoligotyping |
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 information. |
| Traditional settings |
Usual or suspected settings for TB transmission, such as the home or
workplace. See also Nontraditional setting. |
| TST |
Tuberculin skin test. |
| Unique genotype |
A genotype designation that does not match that of any other isolate
in a TB program’s database. |
| Universal genotyping |
The policy of submitting all M. tuberculosis isolates for genotyping.
See Chapter 5, Developing a Tuberculosis Genotyping Program, for
more information. |
| VNTR |
Variable number tandem repeat analysis. VNTR is a type of MIRU analysis.
See also MIRU. |
