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TB Notes 2, 1999

Updates from the Research and Evaluation Branch

Comparable Specificity of Tubersol and Aplisol | Preliminary Findings: Patient-Provider Communication During TB Contact Investigations | Outcomes of TB Contact Investigations

Comparable Specificity of Tubersol and Aplisol - Summary

The following is a summary of a recently published journal article: Villarino ME, Burman W, Wang YC, et al. Comparable specificity of 2 commercial tuberculin reagents in persons at low risk for tuberculous infection. JAMA 1999;281(2):169-171.

The detection of latent TB infection is the basis of preventive therapy and a key indicator of TB transmission. Worldwide, and for more than 60 years, the tuberculin skin test has been used to diagnose latent TB infection. In the United States, two companies manufacture tuberculin for commercial sale: Parkdale Pharmaceuticals, which makes Aplisol, and Pasteur Mérieux Connaught USA, which makes Tubersol. Despite the fact that federal regulations exist for the standardization of tuberculin manufacturing and testing, there have been reports in the medical literature as well as personal perceptions that one or both of these commercial tuberculin reagents may be associated with a high rate of false-positive reactions (i.e., reactions read as positive in persons who are presumed to not be latently infected with TB). To investigate this possibility, we studied the two commercial tuberculin skin test reagents and the standard tuberculin purified protein derivative (PPD-S1) to determine whether either of the commercial reagents is more likely than PPD-S1 to produce false-positive results. PPD-S1 is the nation’s biologic standard for tuberculin PPD and is stored and released for use by the Food and Drug Administration.

We conducted the study at health departments in Denver, CO, Marion County, IN, and Seattle-King County, CA, and universities in Atlanta, GA, San Diego, CA, and Tucson, AZ, and included persons between the ages of 18 and 50, born in the United States or Canada, with no history of exposure to or infection with TB and no known immunodeficiency that would interfere with their ability to react to skin testing. Participants received four tuberculin skin reagents. When they returned to the study site for skin test reading (48 to 72 hours after receiving the injections), two experienced study personnel interpreted and recorded the results using a standard protocol. The study was double blind: each expert test-reader knew neither the identity of the test reagent each participant had received, nor the results of the other reader.

The median age of the study participants was 27, and 65% were female; 49% of participants were students, 69% were white, and most (81%) were born in a western or central U.S. state (also includes Vancouver), with 19% born in an eastern U.S. state (also includes Ontario and Quebec). There were no clinically significant adverse events as a result of skin testing, and of 1,596 persons enrolled, 1,555 (97%) were eligible and included in our analysis. Among our study population, we found that reactions observed after testing with Aplisol were slightly larger (mean = 3.4 mm) than those observed after testing with Tubersol (mean = 2.1 mm). However, these reaction sizes were not significantly different from the reactions observed after testing with PPD-S1 (mean = 2.5 mm), nor did they significantly change the proportion of skin tests interpreted as positive or negative. Assuming that all participants in our study were truly not infected with TB, and using a 10-mm cut-off, our study shows that the specificities of the two commercial products were high (Aplisol = 98.2% and Tubersol = 99.2%) and not significantly different from that of PPD-S1 (98.9%).

Clusters of unexpected positive tuberculin skin test results have been previously reported. However, none of these previous reports involved testing with the two commercial products simultaneously. Thus, the reports cannot exclude the possibility of false-negative reactions associated with one of the products, or of another kind of error associated with tuberculin skin tests when they are not performed under the same conditions. Skin testing variation related to human factors can only be controlled to a finite degree. In clinical practice, these factors cannot be eliminated completely and should always be recognized as potential sources for false-positive tuberculin skin test results. However, the main conclusion of the study is that the choice of commercial product has little impact on test performance and that either product can be used with confidence to correctly classify persons as infected or uninfected with M. tuberculosis.

—Reported by Elsa Villarino, MD, MPH
Division of TB Elimination



Comparable Specificity of Tubersol and Aplisol | Preliminary Findings: Patient-Provider Communication During TB Contact Investigations | Outcomes of TB Contact Investigations

Preliminary Findings from Two Contact Investigation Studies

 1. Patient-Provider Communication During TB Contact Investigations

During 1998, a study was undertaken to explore factors associated with the identification of contacts during contact investigation (CI). Focus groups were conducted at three U.S. sites (San Francisco, CA; San Diego, CA; and Dallas, TX) between August and December. TB staff conducting CI interviews, as well as pulmonary smear-positive patients currently receiving treatment for active TB, were recruited for participation in focus groups. Patients were recruited into one of three groups based on their country of origin and information recorded in their charts: a) U.S.-born patients who identified at most three contacts ("few"), b) U.S.-born patients who identified at least eight contacts ("many"), or c) Mexico-born patients ("Mexico-born"). Patients from Mexico were included in the study to explore their cultural attitudes and behaviors regarding TB and the CI for comparison with the U.S.-born participants. Study objectives were a) to determine what factors are associated with the identification of few contacts, b) to identify patients’ perspectives about CI, c) to identify barriers to eliciting contacts’ names during a CI, and d) to identify staff skills and qualities that are important for successful CI interviewing. Analysis and reporting of the data will be completed in the coming months. Preliminary findings follow.

Thirteen focus groups were conducted with 18 CI staff and 54 patient participants. Of the 31 U.S.-born patients, 65% had a history of substance abuse and 36% had a history of homelessness, according to patient chart records. The median number of contacts identified was two in the "few" group and 12 in the "many" group. By comparison, of the 23 Mexico-born patients, 17% had a history of substance abuse and 13% had a history of homelessness. The median number of contacts identified was six.

Preliminary findings indicate that, despite being currently treated for active TB, patients lacked accurate knowledge about TB and how it is transmitted. Some patients believed that TB could be spread by sharing eating utensils, drinking from the same bottle, and shaking hands with a person with TB. Others, while they did not indicate specific misunderstandings, had many questions regarding risk factors, treatment implications, and even their own diagnosis. With respect to the CI, however, patients showed a good understanding of its purpose and importance. Most patients, including those recruited into the "few" and "substance abuse" groups, claimed to have provided the names of contacts with ease, in spite of the perceived stigma attached to TB and fears of being alienated or losing a job. They expressed feelings of moral and personal obligation to provide the information requested of them. Among the minority of participants who reported reluctance to provide names, fear of alienation, mistrust of the health department, and a sense of invasion of privacy were identified as concerns.

Staff participants emphasized that, in addition to having a nonjudgmental approach, good listening and communication skills were key components of successful CI interviews. Communication with patients from other cultures was noted as one of the biggest challenges for many CI interviewers. When asked about training needs, many reported a desire for training on cross-cultural issues and working with interpreters. Staff also expressed a need for periodic updates on new developments in areas that impact their patients.

These preliminary findings were unanticipated. It was hypothesized that patients recruited into the "few" groups were reluctant to provide names, but the results showed otherwise — that most of the patients reported identifying contacts willingly and with ease. This held true even with groups that had a history of substance abuse and/or homelessness who, according to the information in their charts, had identified three or fewer contacts. One possible explanation is that CI information in the charts was incorrect or incomplete; that is, some names that were provided may not have been recorded because the patient could not provide locating information on the contact. Another possible explanation is that patients and staff may not share the same understanding of what a "contact" is. For example, patients could have readily provided the names of persons with whom they spent time but who were not considered to have been exposed to TB by staff and thus not followed up. This explanation is plausible, particularly in light of the finding that many patients held misconceptions about TB and its transmission. If, for instance, a patient believes TB is spread by drinking from the same bottle, he may identify all of (yet only) his drinking buddies. This would potentially result in the patient’s listing many names and feeling compliant, just as some patients appeared to feel in the focus groups when recalling their behavior in the CI interviews.

The findings from this study will lead to training recommendations. For example, one key finding — that patients, even those who were near completion of therapy, had questions and even misconceptions about TB and how it is transmitted — clearly underscores the importance of communicating and educating effectively on a level that patients understand. CI staff need to make a conscious effort to tailor their language and explanations to the patient and avoid the use of jargon. Staff should be cautious of "information overload," particularly if the CI takes place during the emotional aftermath of a TB diagnosis. Listening carefully while asking the patient to repeat what s/he has understood is essential.

Additionally, heightened cultural sensitivity and awareness are extremely important for successful communication with persons who may have lifestyles, orientations, educational levels, and economic and/or cultural backgrounds different from those of the staff. Working with non–English-speaking foreign-born persons raises further communication challenges, as often the interpreters are family members or friends. To ensure accurate communication, staff should be trained in working effectively with both professional and nonprofessional interpreters.

Although preliminary, the findings from this study illustrate the valuable types of information that can be gained from conducting focus groups. It was known that CI interviews do not always yield contacts, and that the nature and source of the problem needed to be explored. The focused yet flexible characteristic of these groups facilitated obtaining in-depth information about some of the factors associated with the identification of few or no contacts. Using an objective approach, the researchers used guided discussions with both staff and patients to obtain their perspectives on the issue. Typical of focus groups, the findings that have been generated are qualitative and are in the form of opinions and thoughts associated with beliefs, attitudes, and feelings about particular issues — findings that are not ordinarily generated by quantitative epidemiologic studies.

The findings have allowed us to view this CI issue from both the staff’s and the patients’ perspectives. They will be incorporated into training elements and recommended for incorporation into training curricula being developed by the Communications and Education Branch of DTBE. The recommendations may also be used by local health departments to enhance the quality of their CI training programs.

Questions regarding this study should be addressed to Robin Shrestha-Kuwahara at (404) 639-8123.

—Reported by Robin Shrestha-Kuwahara, MPH
Division of TB Elimination



Comparable Specificity of Tubersol and Aplisol | Preliminary Findings: Patient-Provider Communication During TB Contact Investigations | Outcomes of TB Contact Investigations

2. Outcomes of TB Contact Investigations

The Prevention Effectiveness Section of the Research and Evaluation Branch in DTBE collected data from June 1998 through January 1999 for the Outcomes of TB Contact Investigations (CI) Study. The study objectives were to 1) describe the policies and procedures of TB programs and health departments conducting CI, 2) describe outcomes of CI, 3) identify case and contact characteristics affecting outcomes of CI, 4) identify factors associated with preventive therapy (PT) completion for all contacts and high risk contacts, and 5) document resources used in CI. Eleven TB program sites participated, selected to form a representative sample of persons completing preventive therapy: Fulton County, GA; Chicago, IL; Houston, TX; Los Angeles County, CA; Shelby County, TN; New York City, NY; Newark, NJ; San Diego County, CA; San Francisco, CA; Santa Clara County, CA; and King County, WA. This is the first comprehensive study on how contact investigations vary by location, program characteristics, and patient characteristics. Analysis and dissemination of data to the sites will be completed in coming months. Preliminary results follow.

Procedures for CI differed among the sites, including who performs CI, who supervises it, and what data are collected. Contact investigation was performed by outreach workers at six sites, by public health nurses at one site, and by both outreach workers and public health nurses at four sites. TB program personnel directly supervised CI workers at six sites, while other health department staff supervised the workers at the remaining sites. Data collected on contacts varied, since contact classifications and components of summary data forms differed. The most common information collected about contacts included age, gender, and close or casual status, in addition to TB skin test (TST) dates and results, chest x-ray (CXR) date and results, and PT start date. Only two sites recorded the date of a contact's last exposure to the infectious case for determination of follow-up TST date. Risk factors for disease (especially HIV status) and for nonadherence (e.g., substance abuse, homelessness) were not often recorded.

In analyzing data on 13,000 contacts of 1,048 pulmonary, AFB sputum-smear–positive cases, we found a median of five contacts per case (average of 12, range 0-822 contacts per case). Cases listing a greater number of contacts were more likely to be female, foreign-born, or Hispanic. The 88 cases listing zero contacts were more likely to be male, U.S.-born, substance abusers, or homeless persons.

Since all 11 sites either distinguished between close and casual contacts or only recorded data on close contacts, data on approximately 5,100 close contacts were selected for analysis. Of these close contacts, 10% had a history of a positive TST, 11% received no TST, and 79% had a TST placed. Of those having a TST placed, 2% were determined to have active TB, 5% were converters (had an initial negative TST, then a positive TST at follow-up), 33% were newly-identified TST positives, 58% were TST negative, and 2% had unknown TST results. The 58% who were TST negative included those receiving only one TST; 43% of those initially testing negative had no record of a follow-up TST. Of TST positives, 82% were recommended to take PT, of whom 93% started PT. For a third of those started on PT, completion status was either "refused/uncooperative," "lost to follow up," or "unknown." Fifty-seven percent of those started on PT completed, but only 44% of those eligible for PT completed. Those started on PT who didn't complete took a median of 2-3 months before stopping. Asian and foreign-born persons were more likely to complete PT. Children under 6 years of age were not more likely than adults and older children to complete PT. For other high-risk groups (HIV positive, homeless, substance abusers) conclusions cannot be made about PT completion because of limited data. HIV status was known for only 13% of close contacts analyzed. Only half of all close contacts known to be at high risk for disease (HIV positive, children aged 5 or younger, diabetics) were placed on presumptive treatment for latent TB infection, regardless of TST result.

From these preliminary results, several conclusions can be made. First, there is a need to determine common elements of data collection for contacts, especially high-risk factors for disease and nonadherence. Second, CI training curricula need to address differences in testing, placement on PT, and follow-up through completion of therapy. Third, interviewing skills should be assessed for identifying contacts among U.S.-born persons, males, substance abusers, or homeless persons. Fourth, a strategy for assessing all contacts, both TST negative and TST positive, for high-risk factors should be developed. Fifth, HIV counseling, testing, and coordination of care for contacts at risk for HIV should be provided, along with presumptive treatment of latent TB infection for known HIV-positive persons. Sixth, contacts need to be prioritized by high-risk status and followed up through PT completion accordingly. Ensuring PT completion is part of the contact investigation process. And finally, methods to evaluate the quality of CI need to be developed.

The finding that foreign-born contacts were more likely to complete PT than U.S.-born contacts bodes well for TB control in the United States, given that each year a larger percentage of U.S. cases are foreign born (and foreign-born cases are likely to have foreign-born contacts). However, since 95% of contacts were placed on self-administered, rather than directly observed, preventive therapy, we don't know with certainty whether foreign-born contacts were more likely to have completed or were more likely to have reported completing PT.

Completion rates may be higher with a 2-month PT regimen, based on the observation that half of those who did not complete PT managed to take 2-3 months of therapy prior to stopping. Current CDC/ATS recommendations include shorter alternatives to a 9-month INH PT regimen for HIV-positive adults: 1) a daily 2-month rifampin and pyrazinamide regimen for those not taking protease inhibitors, and 2) a daily 2-month rifabutin and pyrazinamide regimen for those taking certain protease inhibitors. While new guidelines are being developed, a 2-month regimen may also be used as an alternative to the standard 6-month INH regimen for HIV-negative adults, especially in settings where provision of longer courses of preventive therapy has not been feasible (i.e., jails). A standard 2-month regimen for adult contacts, regardless of HIV status, should be investigated to determine its programmatic effectiveness and cost.

Provider knowledge of HIV status is essential for the optimal provision of treatment for latent TB infection, given its recommendation for HIV-positive contacts regardless of age, TST results, or history of previous PT. HIV status is also needed to determine the proper drug regimen for HIV-positive adults and for the coordination of care overall. Ideally, TB program staff should be trained and prepared to offer HIV counseling and testing to close contacts at risk for HIV.

In the next few months, analysis of resources used during contact investigation and of organizational factors associated with successful CI outcomes will be presented. Questions regarding the study should be addressed to Suzanne Marks, principal investigator, or Zach Taylor, co-principal investigator, at (404) 639-8123.

—Reported by Suzanne Marks, MPH, MA
Division of TB Elimination


Released October 2008
Centers for Disease Control and Prevention
National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention
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