TB Notes Newsletter

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Clinical and Health Systems Research Branch Updates

Study 26 Reaches Enrollment Goal

Study 26 has reached its patient enrollment goal. As of 2:32 pm on January 29, 2008, the Tuberculosis Trials Consortium (TBTC) was very happy to report that 8000 patients were enrolled in USPHS/TBTC Study 26. TBTC wishes to thank the volunteer patients, community members, health professionals, and scientists involved in conducting and supporting this study.

—Reported by Elsa Villarino, MD
Div of TB Elimination

Tuberculosis Diagnosis at Death Among HIV-Infected Persons: US Metropolitan Statistical Areas, 1998–2003

TB remains a potentially deadly disease for those living with HIV infection. Deaths can occur during TB treatment, or prior to TB disease diagnosis, which is referred to as “TB diagnosis at death.” HIV increases the risk of death during TB treatment, especially for those having multidrug-resistant (MDR) TB. National TB Surveillance System data for 1997–1999 show that 40% of HIV-infected persons with MDR TB died during treatment, compared with 8% of HIV-uninfected persons with MDR TB (Moore M, unpublished data, January 2003). Analysis of National TB Surveillance System data excluding California from 1997 to 2005, adjusted for MDR TB, age, residency in a longterm care facility, US birth, race/ethnicity, sex, substance abuse, and other disease characteristics indicates that HIV-infected persons’ odds of death during TB treatment was five times higher than that of HIV-uninfected persons (Marks SM and Magee E, unpublished data, March 2008). The same study also revealed that HIV-infected patients had a five times greater odds of being diagnosed at death, adjusted for age, US birth, sex, race/ethnicity, and other disease characteristics. The current study examines trends in TB diagnosis at death among HIV-infected persons in the 10 most HIV-prevalent US metropolitan statistical areas (MSAs) during 1998–2003. Diagnosis of TB at death may reflect lack of ready access to TB or HIV prevention, diagnosis, and treatment services. Identifying groups or areas with high rates of TB diagnosis at death in HIV-infected persons may help pinpoint disparities in access to HIV care, access and provision of TB care, or both.

To identify those diagnosed at death, we used 1998–2003 data on “status at diagnosis of TB” from the National TB Surveillance System for 20 MSAs having the highest reported TB/HIV co-morbidity in numbers of patients. We report results individually, but anonymously, for the top 10 MSAs having the highest TB/HIV co-morbidity. HIV status was classified into positive (from a documented test, previous HIV/AIDS diagnosis, or self report), negative (from a documented test within the past year), or unknown (indeterminate results, refused testing, not offered testing, results unknown, unknown). We first compared the risk of being diagnosed with TB at death for HIV-infected versus HIV-uninfected patients (excluding those from the three California sites since the state of California only provides CDC access to AIDS case registry and TB registry matching results; data are limited to reported AIDS cases, and exclude HIV negativity or unknown status). Then, we examined those groups of TB patients having unknown HIV status, comparing those diagnosed at death with those diagnosed while alive. For known HIV-infected TB patients, we then identified factors associated with TB diagnosis at death by using multivariate log-binomial analysis to obtain adjusted prevalence ratios.

In rank order from highest to lowest prevalence, the top 10 TB/HIV-prevalent MSAs were New York City, Miami, Los Angeles, Houston, Chicago, Atlanta, Ft. Lauderdale, Newark, Dallas, and Washington, DC. In these 10 MSAs, TB/HIV patients comprised 14% of all TB patients, or 25% of those with known HIV status (range: 7%–32% of all patients or 17%–37% of patients with known HIV status). HIV-infected TB patients in the top 10 MSAs had the following demographics: male (72%), non-Hispanic black (58%), foreign born (36%), Hispanic (25%), missing race/ethnicity (8%), non-Hispanic white (7%), Asian/Pacific Islander (2%), age 65 or over (2%), and American Indian/Alaska Native (0.1%).

Regardless of HIV status, 2.0% of all patients in the top 10 MSAs were diagnosed with TB at death (range: 1.0%–3.4%). The percentage of HIV-infected TB patients who were diagnosed at death varied from year to year by MSA, but appeared to decline over time. The median and average TB diagnoses at death per year for HIV-infected patients in the top 10 MSAs was 3.2%, but averaged 6.6% in MSA 10; 5.6% in MSA 3; and 4.4% in MSA 6.

HIV-infected patients had on average 4.9 times (95% confidence interval [CI]: 3.8-6.2) greater risk than HIV-uninfected patients to have been diagnosed at death (vs. while alive) during 1998–2003. This significantly greater unadjusted risk of TB diagnosis at death for HIV-infected patients was true at all but one of the MSAs (RR range 2.7–8.4) (Figure).

Those diagnosed at death were 1.75 times (95% CI: 1.64-1.86) more likely to be missing HIV status information. This association held true for seven of the nine highest non-California TB/HIV-prevalent MSAs, with RRs ranging from 1.6 to 11.5. We found that Asians (RR=1.6, 1.5–1.6), non-Hispanic whites (RR=1.4, 1.3–1.4), and foreign-born persons (RR=1.1, 1.05–1.12) were significantly more likely, and non-Hispanic blacks (RR=0.6, 0.6–0.7), males (RR=0.8, 0.78–0.83), and Hispanics (RR=0.9, 0.86–0.92) less likely to have unknown HIV status.

From multivariate analysis, we found (as expected) that HIV-infected TB patients aged 65 or over had 3.7 times greater risk of diagnosis with TB at death than younger HIV-infected patients. HIV-infected Hispanics had half the risk as non-Hispanics and HIV-infected foreign-born patients had nearly half the risk as US-born patients to be diagnosed at death. In three MSAs, there was a 2.1-2.7 times greater risk of being diagnosed at death than in the remaining MSAs. In one MSA, there was a 70% lower risk of diagnosis at death than in the other MSAs. MDR TB was not significantly associated with being diagnosed at death, nor was TB disease that was strictly extrapulmonary.

The following limitations apply to this study. Deaths during TB treatment or TB diagnoses at death may not be deaths caused by TB, which requires verification through autopsies (which have declined from 41% of hospital deaths in 1961 to 5%–10% in the mid-1990s in the United States)1, from specimens obtained just prior to death, or from lab results received after death. In Italy, an autopsy study of 350 AIDS patients found 20 (6%) patients with TB were undiagnosed while alive.2 In the absence of US autopsy studies, one US study found that 22% of a 1997 TB/HIV cohort died, and 44% of the deaths were from TB; the study used sputum smears at death to diagnose pulmonary TB and tissue cultures for extrapulmonary TB.3 Some sociodemographic factors of known HIV-infected patients could not be examined because some data were missing for those diagnosed with TB at death: data on injecting and noninjecting drug use for 28%-29%, and data on alcohol abuse for 29% (compared with 5%-6% missing data for those factors of those diagnosed while alive). Similarly, we found that homelessness data were missing for 9% of those dead at diagnosis (vs. 3% of those alive), residence in a longterm care facility data for 2% (vs. 0.2% of those alive), and residence in a correctional facility data for 1% (vs. 0.2% of those alive).

While TB mortality in HIV-infected persons has declined over time because of reductions in US TB incidence and prevalence, implementation of highly active antiretroviral therapy (HAART),4,5 and improvements in TB and HIV case management,6 HIV-infected TB patients had nearly five times the unadjusted risk of being diagnosed with TB at death as HIV-uninfected persons in the highest TB/HIV-prevalent MSAs from 1998–2003. Among HIV-infected persons, TB patients aged ≥ 65 years had three times the risk of younger patients, and those residing in three high TB/HIV-prevalent areas had risks of diagnosis at death two to three times higher than those in other areas.

TB diagnosis at death reflects both the risk of death with undiagnosed TB and the risk of a diagnosis of TB after death. HIV-infected patients aged 65 or older might have a greater risk of death with undiagnosed TB because of missed diagnoses due to age-related immunosuppression,7 which reduces the sensitivity of the tuberculin skin test (TST) and results in atypical clinical and radiographic presentation. On the other hand, HIV-infected Hispanics were half as likely to be diagnosed with TB at death as other race/ethnic groups, and foreign-born patients 40% as likely. To possibly explain this, first we note that diagnosis of TB after death generally requires either a specimen taken for examination just prior to death or an autopsy (half of which are performed when patients die in or upon arrival at a hospital).8 Second, uninsured TB patients stay fewer days in a hospital9 and are less likely than those insured to have usual diagnostic services and access to care. Thus, it is possible that Hispanics, who are less likely to have insurance than other groups,10 were not hospitalized or examined prior to death or autopsied after death. Alternatively, it is possible that Hispanics are more likely to be diagnosed with TB while alive because of frequent screening efforts taking place in Hispanic or foreign-born communities because of immigration requirements. We might expect both of the above-mentioned possibilities to be occurring.

Additional data collection is needed for those diagnosed with TB at death. The extent to which autopsies include HIV testing is unknown. Post-mortem medical record reviews may help achieve completion of data collection on alcohol abuse, injecting drug use, or noninjecting drug use. Efforts are needed to obtain missing information on homelessness, residence in a long-term–care facility, or residence in a correctional facility for known HIV-infected TB patients diagnosed at death.

Since a diagnosis of TB at death is a late diagnosis, it should be considered a sentinel event for evaluation of missed prevention opportunities. Alternatively, favorable practices should be identified at locations where there are lesser risks of diagnoses at death. Among TB patients, routine voluntary HIV testing (including opt-out testing in clinical settings) and referral to HIV care are needed, along with routine screening of known HIV-infected persons for symptoms of TB disease, testing for latent TB infection (LTBI), and LTBI treatment completion to prevent deaths in HIV-infected persons at risk for TB. It may also be helpful to track the effect of HAART on reductions in TB diagnosed at death among HIV-infected persons.

—Reported by Suzanne M. Marks, MPH, MA;
Todd Wilson, MS; and Valerie Robison, DDS, PhD

References

1. CDC, National Center for Health Statistics. The autopsy, medicine, and mortality statistics. Vital and Health Statistics 2001;3(32):1.
    
2. D’Arminio Monforte A, Vago L, Gori A, Antinori S, Franzetti F, Antonacci CM, Sala E, Catozzi L, Testa L, Esposito R, Nebuloni M, Moroni M. Clinical diagnosis of mycobacterial diseases versus autopsy findings in 350 patients with AIDS. European Journal of Clinical and Microbiological Infectious Diseases 1996; 15(6):453-8.
    
3. Leonard MK, Larsen N, Drechsler H, Blumberg H, Lennox JL, Arrellana M, Filip J, and Horsburgh CR. Increased survival of persons with tuberculosis and human immunodeficiency virus infection, 1991-2000. Clinical and Infectious Disease 2002;34:1002-1007.
    
4. Jones JL, Hanson DL, Dworkin MS, DeCock KM, and the Adult/Adolescent Spectrum of HIV Disease Group. HIV-associated tuberculosis in the era of highly active antiretroviral therapy. The adult/adolescent spectrum of HIV disease group. International Journal of TB and Lung Disease 2000;4(11):1026-1031.
    
5. The Antiretroviral Therapy Cohort Collaboration. Incidence of tuberculosis among HIV-infected patients receiving highly active antiretroviral therapy in Europe and North America. Clinical Infectious Diseases 2005;41:1772-1782.
    
6. Munsiff SS, Ahuja SD, Driver CR. Public-private collaboration for multidrug-resistant tuberculosis control in New York City. International Journal of Tuberculosis and Lung Disease 2006;10(6):639-648.
    
7. Nijhuis EW, Nagelkerken L. Age-related changes in immune reactivity: the influence of intrinsic defects and of a changed composition of the CD4+ T cell. Exp Clin Immunogenetics 1992;9(4):195-202.
    
8. Hoyert DL, Kung HC, Xu J. Autopsy patterns in 2003. National Center for Health Statistics. Vital Health Statistics 2006;20(32).
    
9. Marks SM, Taylor Z, Ros Burrows N, Qayad MG, Miller B. Hospitalization of homeless persons with tuberculosis in the United States. American Journal of Public Health 2000;90(3):435-438.
    
10. CDC. Health disparities experienced by Hispanics–United States. MMWR 2004;53(40):935-941.

New Publications Available Soon!

Look for a new series expected to be released over the next few months, entitled Promoting Cultural Sensitivity: A Practical Guide for Tuberculosis Programs Providing Services to Foreign-born Persons. The series comprises five modules, each focused on a distinct cultural group: Chinese, Hmong, Mexican, Somali, and Vietnamese. Each guide contains chapters on the selected group’s history and immigration; culture; health issues; and common perceptions, attitudes, and beliefs about TB. A product of DTBE’s 2003 ethnographic study of foreign-born persons in the United States, the series aims to help TB program staff provide culturally competent TB care to some of our highest priority foreign-born populations.

Intended Audience

Intended for health care providers, community-based workers, program planners, administrators, health educators, and resettlement agencies that work with the five selected foreign-born populations, the guides are designed to increase the knowledge and cultural sensitivity of providers serving these populations. The ultimate aim is to foster culturally competent TB care and services for foreign-born populations in the United States.

About the Guides

Each guide in the series includes the following:

• A 2-page summary of program tips
• Chapters on history and immigration; culture; health issues; and common perceptions, attitudes, and beliefs about TB
• A concluding summary
• Appendices, including additional resources for working with TB patients and interpreters and a glossary of terms
• Useful resources
• References

Some of the information in the guides, such as the practical tips, can be applied directly, while other sections are more informative and will help providers better understand the background and sociocultural context of the population. A deeper understanding of pertinent issues will heighten the cultural sensitivity of TB care providers, enhance communication, and improve the overall effectiveness of organizations and staff in cross-cultural settings.

The content of these guides was gathered in two ways. First, an in-depth review of TB-related epidemiologic, behavioral, and ethnographic literature on the cultural group was performed. Secondly, in 2003, DTBE undertook a qualitative study to describe ethnographic aspects of the increasing burden of TB among five foreign-born populations. Selected major findings from the study are presented in each of the guides.

The Hmong guide will be the first to be released, followed by the Somali guide. All guides are expected to be in print by late spring or early summer. Limited hard copies and CD-ROMS will be available. PDF versions of the guides will be accessible on the DTBE website, starting with the Hmong guide . (PDF)

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