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TB Notes 3, 2003
UPDATES FROM THE SURVEILLANCE, EPIDEMIOLOGY,
AND OUTBREAK INVESTIGATIONS BRANCH
Plans for Implementation of Universal TB
CDC anticipates that the Universal TB Genotyping Program will be
implemented by fall 2003. CDC will contract with laboratories to
serve as national resources for the provision of TB genotyping services.
The laboratories will perform rapid polymerase chain reaction (PCR)
tests on at least one isolate for every culture-positive case and,
when requested by TB control programs, will perform IS6110-based
restriction fragment length polymorphism (RFLP) on isolates that
match by PCR.
Universal access to rapid diagnostic tools for identifying the
similar genetic strains among persons with TB should greatly enhance
TB control programs and promote the elimination of TB. The use of
genotyping to differentiate Mycobacterium tuberculosis (Mtb)
strains has been shown to improve TB control in a number of ways.
For example, genotyping has enhanced and expedited contact investigations
(CIs) by demonstrating unsuspected relationships between patients,
identifying new and unusual settings of transmission, and establishing
priorities in CIs. Genotyping has assisted in the control of outbreaks
by allowing them to be detected earlier, promoting thorough investigations,
and again, establishing priorities in CIs. Genotyping has also helped
identify cross-jurisdictional transmission and laboratory cross-contamination,
and has been used to evaluate patterns and prevalence of Mtb strains.
Finally, genotyping has been used as a tool to evaluate TB control
efforts. Completeness of routine CIs can be assessed, and progress
toward TB elimination can be evaluated (by the monitoring of genetic
clustering as a surrogate marker for recent TB transmission). The
recently-ended National TB Genotyping and Surveillance Network (NTGSN)
project, a pilot project undertaken to evaluate the usefulness of
genotyping in TB control settings, provided a wealth of information
about this technology. The success of this project demonstrated
the value of using IS6110-based RFLP for TB control and paved
the way for this current programmatic effort. Rapid new PCR tests
for TB genotyping hold even greater promise for promoting TB control.
The National Tuberculosis Controllers Association (NTCA) and CDC
have established a technical advisory and planning workgroup that
provides advice regarding the development of the framework and infrastructure
of the Universal TB Genotyping Program to ensure its effective operation.
In order to help TB control programs maximally use the opportunity
of universal genotyping, we are developing user-friendly protocols
and flow diagrams that will help programs address technical, logistical,
laboratory, and epidemiologic issues, and we are also developing
an NTCA/CDC Guide to the Application of Genotyping to Tuberculosis
Prevention and Control (see next article). In addition to the
Guide, TB programs will be provided with templates to help them
develop program implementation plans for genotyping. The templates
for such plans as well as forms and updates to the Guide will be
posted on the Web board.
In addition, we plan to perform operational research in order to
pilot test universal genotyping. The pilot test would evaluate protocols,
data elements, and functional requirements for systems for the collection
and transmission of data between partners, integration of genotyping
and program data to ensure that genotyping results are readily accessible
for field application, and tracking and notification of specimens
and results. The additional costs of a genotyping program would
also be quantified.
We hope these steps will build the foundation for effective implementation
of universal genotyping, which holds great promise for enhancing
TB control and prevention.
—Reported by Lisa Rosenblum, MD
Div of TB Elimination
Guide to the Application of Genotyping to
Tuberculosis Prevention and Control:
A Handbook for TB Controllers, Epidemiologists,
and Other Program Staff
In 1996, CDC established the National Tuberculosis Genotyping and
Surveillance Network (NTGSN) to determine the usefulness of specific
genotyping techniques in understanding the epidemiology of TB in
the United States (Castro KG, Jaffe HW. Emerg Infect Dis
2002;8:1188-91). Some of the results of this 5-year project were
published in a special issue of Emerging Infectious Diseases
in November 2002.
The success of NTGSN and the experience gained from it led to a
commitment by CDC to support the implementation of universal genotyping
of Mycobacterium tuberculosis isolates, i.e., the genotyping
of at least one isolate from every culture-positive case in the
United States. After the implementation of universal genotyping,
TB programs will receive genotyping results on all initial patient
isolates within 2 weeks of submission of the isolate for typing.
CDC recognizes that building laboratory capacity at the state and
local levels is crucial to the implementation of universal genotyping.
Policies and procedures to enable TB program staff to interpret
genotyping results correctly and to respond effectively to results
To coordinate the building of TB program capacity for interpreting
and responding to genotyping results, the National Tuberculosis
Controllers Association (NTCA) and CDC formed a workgroup on genotyping.
Members of that group are developing a Guide to the Application
of Genotyping to Tuberculosis Prevention and Control to provide
direction toward understanding genotyping and how it can be used
in routine TB prevention and control practices. It is hoped that
this Guide will serve as the first step in the implementation of
The Guide is organized as follows: Section 1, Overview of the
Genotyping Process, describes how genotyping of M. tuberculosis
is accomplished. Section 2 explains how the universal genotyping
program will be implemented and how universal genotyping will provide
timely results to TB programs. Interpreting genotyping results is
covered in Section 3, and how to apply results to TB prevention
and control practices is detailed in Section 4. Specific information
about developing a state plan to implement universal genotyping
is provided in Section 5. Appendices A and B contain a glossary
and a list of useful resources.
Currently the Guide is being reviewed by the members of the workgroup.
After incorporating comments from reviewers, we plan to publish
the Guide in the early fall of 2003.
—Reported by Scott J.N. McNabb, PhD, MS
Div of TB Elimination
Enhanced Surveillance to Identify Missed
Opportunities for TB Prevention in the Foreign-born: Closing the
The first study involving all 22 sites of the Tuberculosis Epidemiologic
Studies Consortium (TBESC) will begin this fall. The study’s goal
is to identify missed opportunities for TB prevention in foreign-born
persons, the population that now accounts for more than half of
the TB cases reported annually in the United States and Canada (currently
about 15,000 for the United States and approximately 2,000 in Canada).
This will be the first large population-based epidemiologic study
of TB in foreign-born persons in the U.S. and Canada. It will involve
in-person interviews with approximately 1,500 persons in 16 states
and two Canadian provinces. The three co-principal investigators
for the study are Amy Davidow, Ph.D., assistant professor of preventive
medicine and community health, New Jersey Medical School; Randall
Reves, M.D., medical director, Denver Metro Tuberculosis Clinic,
and president, National TB Controllers Association; and Dolly Katz,
PhD, senior epidemiologist, Division of Tuberculosis Elimination,
The TBESC was established in September 2001 to conduct TB research
and to strengthen TB public health infrastructure in the U.S. and
Canada. The sites include academic institutions, medical centers,
and TB control programs across the U.S. and Canada. The TBESC currently
has 13 research projects in development or underway.
The TBESC selected the epidemiology of TB in foreign-born persons
as a top research priority because of its critical importance to
TB elimination in the U.S. and Canada. In the past decade, TB in
North America has increasingly become a disease of persons born
outside the U.S. and Canada. In 2002, for the first time, TB cases
among foreign-born persons accounted for the majority (51%) of the
15,078 TB cases reported in the United States. In Canada, foreign-born
persons have accounted for the majority of TB cases since 1990.
The reason for the increasing concentration of TB among foreign-born
persons is that TB case numbers and rates have dropped much more
sharply among native-born persons than among foreign-born persons.
Among U.S.-born persons, for example, TB rates per 100,000 persons
dropped from 8.2 in 1992 (19,225 cases) to 2.8 in 2002 (7,252 cases),
a decline of almost 66%. Rates among foreign-born persons were 34.5
(7,270 cases) in 1992 and 23.6 (7,544) in 2002, a 31.6% decline.
The goal of the TBESC study of TB in foreign-born persons is to
close that gap.
As with native-born persons, reducing the incidence of TB among
foreign-born persons depends upon increasing the yield from the
three basic TB control activities of (1) detection and treatment
of active TB, (2) contact investigations, and (3) targeted testing
and treatment for latent TB infection.
However, these activities need to be tailored to the special circumstances
of foreign-born persons, which often involve complicating factors
such as visa status, drug resistance, social and economic hardships,
linguistic barriers, and cultural beliefs that deter diagnosis and
interfere with adherence to therapy and cooperation with contact
investigations. Although current national surveillance data for
the U.S. and Canada have identified the increasing importance of
TB among the foreign-born, these data lack the level of detail needed
to identify the proportion of TB cases that could have been prevented
by improvements in each of the three basic TB control activities.
The TBESC study will focus on in-person interviews with a random
sample of approximately 1,500 foreign-born persons living in the
22 sites of the Tuberculosis Epidemiologic Studies Consortium (TBESC)
who were diagnosed with TB in 2003-2004. Epidemiologic data collected
for each case will describe the means of diagnosis (through screening
for disease or due to symptomatic disease), time from arrival to
disease onset to diagnosis and initiation of treatment, immigration
status, country of origin, migration in the U.S. or Canada, access
and barriers to care (including insurance coverage and cultural
barriers), treatment outcomes, and other information that will shed
light on missed opportunities for prevention. Additional information
will be collected from health department records, national surveillance
databases, and record linkage with CDC’s Division of Global Migration
The study’s protocol development team includes a community representative
who will help craft the protocol and questionnaire with an eye to
the concerns and sensitivities of persons from different cultural
and linguistic backgrounds. In addition, the team is seeking advice
from community outreach groups on how best to inform the target
communities about the upcoming project and encourage their participation.
Data obtained from case interviews will provide unique epidemiologic
information collected consistently from site to site. These data
will be used to identify interventions that can improve each of
the three basic TB control activities and inform public health efforts
to eliminate TB among foreign-born persons in the U.S. and Canada.
—Reported by Dolly Katz, PhD
Div of TB Elimination