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U.S. Department of Health and Human Services

  

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TB Notes 3, 2003

UPDATES FROM THE SURVEILLANCE, EPIDEMIOLOGY, AND OUTBREAK INVESTIGATIONS BRANCH

Plans for Implementation of Universal TB Genotyping

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 are essential.

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 universal genotyping.

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 Gap

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, CDC.

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 and Quarantine.

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

 


Released October 2008
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