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TB Notes Newsletter

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No. 4, 2011


19th Semiannual Meeting of the Tuberculosis Epidemiologic StudiesConsortium (TBESC)

The legacy of the Tuberculosis Epidemiologic Studies Consortium’s (TBESC) first decade is not only the body of scientific and epidemiologic research produced by its members, but also the awareness that TB research can improve the ability to perform TB control, according to Bob Horsburgh, MD, TBESC co-chair. This, the 19th Semiannual Meeting, was marked not only by scientific sessions to discuss current research, but also by a look-back at important findings over the lifetime of the consortium. Approximately 150 principal investigators, project coordinators, and other TBESC personnel attended the meeting July 20–21, 2011, in Chicago. Meeting participants focused on the steps needed to bring current projects to completion, and on lessons learned over the last 10 years. The Chicago meeting was the final meeting of the first TBESC; members discussed both the past 10 years, as well as the future of TB and LTBI research.

Day one’s scientific sessions featured presentations of current TBESC study results. One highlight of the first day’s presentation was new data from the study “Integration of Mycobacterium tuberculosis genotyping into routine TB program practice: Testing and refinement of a method to prioritize clusters for investigation.” This study was performed to determine the best way to prioritize investigation of two or more TB patients with identical genotypes, or clusters. Determining the best method of cluster prioritization is important in order to determine which clusters likely represent recent transmission and the potential for a larger outbreak, and which ones are unlikely to pose an increased risk for transmission. Wendy Cronin, PhD, reported that of 44 clusters randomly selected among three sites for investigation, 164 epidemiologically linked TB case pairs were identified. In 11 clusters, there were no identified epidemiological links between patients. Of identified epidemiologically linked pairs, 45% occurred in congregate settings, 20% in close social settings, 18% in nonresidential areas, and 17% in household settings. Next steps for the study include evaluating whether the time between cluster cases plays a role in the priority assigned to the cluster.

A study to assess the performance and agreement between the tuberculin skin test (TST) and interferon gamma release assays (IGRAs) in 2- to 14-year-old children immigrating from Vietnam, Mexico, and the Philippines found that 26% of children applying for immigration tested positive by TST, compared to only 6% testing positive by QuantiFERON Gold In-Tube (QFT). Meredith Howley, project coordinator for the study, reported that agreement between the two tests was 74%; positive results increased with age for both tests. Future analysis for this study includes evaluation of the association between the TB status of the family, and the child’s QFT and TST results.

At the end of day one of the conference, participants attended a welcome reception, as they had after the first day of previous TBESC meetings. However, the welcome reception for the final TBESC meeting featured the ukulele, played by Hawaii Field Medical Officer Dick Brostrom; the flute, played by CDC Medical Officer John Jereb; a trivia contest; and a mashed potato bar. A good time was had by all.

On the second day of the conference, presenters provided a retrospective of TBESC findings over the previous 10 years. Paul Colson, PhD, discussed “Improving LTBI Treatment Outcomes.” He stated that a TBESC research intervention to increase the knowledge of physicians in the importance of LTBI treatment was valuable in teaching them the risk of LTBI progression in HIV-infected persons, the interpretation of the TST, and the appropriateness of isoniazid (INH) in all age groups. Another study, performed at all TBESC sites, was designed to find factors associated with acceptance and completion of LTBI treatment. Phase Two of the study found that about 53% of all patients failed to complete treatment; factors associated with failure to complete treatment included a 9-month INH regimen, and being a healthcare worker. Phase Three of the study found that persons who reported that the clinic schedule was not inconvenient, or only slightly inconvenient, were more likely to accept LTBI treatment than persons who reported the schedule was a major inconvenience. Persons with stable housing were 1.7 times more likely to complete LTBI treatment than person who did not report stable housing.

Randall Reves, MD, presented TBESC findings pertaining to TB elimination in the foreign-born and U.S.-born African Americans. He reported that a TBESC study designed to identify missed TB prevention opportunities in the foreign born found that over 85% of foreign-born persons diagnosed in the first year after U.S. entry were diagnosed as a result of screening due to TB symptoms or immigration screening. Of those diagnosed in the first 3 months after U.S. entry, immigration screening was the most likely source of diagnosis. Conversely, in a TBESC study, “National Study of Determinants of Early Diagnosis, Prevention, and Treatment of TB in the African-American Community,” Dr. Reves stated that diagnosis of TB in African Americans occurred due to routine care, screening, or treatment for a comorbid condition, or as a result of a contact investigation.

Other highlights from the second day of the conference included updates from the Publications and Presentations Committee, the Translating Research into Practice Workgroup, and the External Relations Committee.

—Reported by Suzanne Beavers, MD, and Dolly Katz, PhD
Div of TB Elimination

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Steps to Ensure Genotyping Success for TB Programs

Genotyping of culture-positive TB isolates can provide valuable information to state TB programs with regard to TB epidemiology within local populations, TB transmission, multi-jurisdictional clustering, and identification of false-positive specimens. This information can assist in defining program priorities for surveillance, case management, and education and training at state and local levels.

In 1996, the Maryland Center for Tuberculosis Control and Prevention (CTBCP) initiated genotyping of culture-positive TB patients, with a goal that every resident with culture-positive TB would have an isolate genotyped. In 2009 and 2010, the goal was reached and 100% of all Maryland TB culture-positive isolates were genotyped. How this goal was accomplished, and how other states can meet this same goal, is demonstrated below.

Success is dependent upon fostering good, sustainable working relationships among the State Mycobacteriology Laboratory, CTBCP, and private sector hospitals and laboratories. The guiding principle of these relationships was a commitment to improve the public health of all Maryland residents who have contracted TB, through testing, diagnosis, and treatment. Maryland maintains and fosters these relationships through frequent communication both by telephone and fax with all partners, including private providers, hospital laboratories, public laboratories, and county health department staff.

The State Genotyping Coordinator is based within the CTBCP. The State Genotyping Coordinator maintains the database with all the genotyping test results, clusters, and pertinent patient information.  The State Mycobacteriology Laboratory has identified a coordinator, who maintains the isolates on all genotyped patients and collects isolates from private laboratories on Maryland residents. Each coordinator has his or her specific roles and tools to use, and these individuals work closely together.

The State Laboratory Coordinator prepares and sends isolates to the reference genotyping laboratory in Michigan monthly, and provides a list of outgoing isolates to the State Genotyping Coordinator.  The State Genotyping Coordinator enters the names and other pertinent data into the local genotyping database. Both coordinators have access to TB GIMS. Genotyping reports are received by both the laboratory and program coordinators, and results entered into the local database. The genotyping coordinator then assumes primary responsibility for contacting and consulting with local health departments regarding potential links within clusters.  Any suspicions of or questions arising from possible multi-jurisdictional clusters are referred to the CTBCP program chief. Suspected laboratory contaminations are referred by the program genotyping coordinator to both the local health department and the CTBCP program chief for follow-up.

Genotyping begins with the CTBCP surveillance staff generating a list of all culture-positive TB cases for the current year. The list is updated monthly and sent to both the Genotyping Coordinator and the Mycobacteriology Laboratory Coordinator. This list contains the patient’s name, county of residence, and date of culture identification, and indicates if the culture was identified as TB at the state or other laboratory. Other laboratories include private hospitals, commercial or university laboratories, and other public laboratories in other states. The genotyping and laboratory coordinators regularly discuss which isolates have not been received from other laboratories, and determine who will take responsibility for requesting individual isolates from which laboratories to be sent to the State Mycobacteriology Laboratory.

For those isolates not already received at the State Laboratory, the Genotyping Coordinator contacts the local health department(s) to obtain a copy of the laboratory report form for the patient’s TB positive culture. This form provides the name of the laboratory that processed the specimen, the patient’s name and date of birth, the healthcare provider or center that requested the test, the laboratory accession number for the specimen, and the date the specimen was processed.

Several tools have been developed to request specimens from other laboratories. The first tool is a directory that contains the names and contact information of all private and public laboratories that have processed Maryland TB case specimens, the name of each laboratory supervisor or contact person, and their direct telephone and fax numbers. The directory is amended as new laboratories, hospitals, or other institutions are identified that collect or process specimens for Maryland TB cases.

The second tool is a standardized isolate requisition form used for requesting isolates from other laboratories. It contains the patient’s name and date of birth, specimen type and date of specimen collection, and laboratory accession number to help identify the correct specimen needed from the laboratory. The request form also contains space for the laboratory name, address, contact person and their numbers. Lastly the form has the State Mycobacteriology Laboratory Chief’s name, and mailing address for shipping purposes.

For example, when a positive TB isolate needs to be retrieved from a private laboratory, a coordinator calls the facility contact person directly. Once the location of the specimen is confirmed, a requisition form is faxed to the contact person so that the isolate is shipped to the Maryland State Mycobacteriology Laboratory. Sometimes the private laboratory is unaware that the patient is a Maryland resident, or may have sent the isolate to another laboratory instead.  The time spent building relationships with the specific contact personnel working in outside laboratories ultimately saves time and avoids confusion.  These relationships have proven very helpful when false-positive results are suspected. Regular contact makes communication much easier.

Tracking down positive TB cultures processed in other laboratories across the United States is a time-consuming process.  Since 1996, isolates have been obtained from more than 75 laboratories.  In October 2008, Maryland regulators eased the TB isolate tracking process by changing Maryland state regulations.  This third tool, the revised Maryland code (COMAR) C, states that a positive TB culture from a Maryland resident must automatically be sent to the Maryland State Mycobacteriology Laboratory for testing and processing.  This regulation has decreased the number of requests made to larger laboratories, but smaller ones still need reminding.

In 2010, only 93 (57%) isolates from 162 culture positive cases were processed in the State Mycobacteriology Laboratory. The other 69 specimens were processed at private Maryland hospitals, out-of-state hospitals, and commercial or out-of-state laboratories. Using the system described enabled the Maryland State Mycobacteriology Laboratory to retrieve all 162 isolates for genotyping. 

The success of Maryland’s Genotyping Program is a direct result of 17 years spent fostering strong, collaborative working relationships with local health departments, public and private laboratories, and hospitals nationwide.  The development and implementation of a protocol that provides routine access to a surveillance list of culture-positive cases, the laboratory directory, an isolate request form, and the 2008 regulations has provided tools that Maryland has relied on for continued success in the genotyping program.  The national TB GIMS program is another communication resource that provides names and contact information from other public laboratories. The utility of TB GIMS will ensure continued success for Maryland’s Genotyping Program in the future.

—Submitted by Heather Rutz, MCRP, MHS and Rachel A. Vaden
Maryland Department of Health and Mental Hygiene

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