Faculty Bibliography

OBJECTIVES/OBJECTIVE:Initiation of antiretroviral therapy (ART) and the 3I's are strategies to prevent HIV-associated tuberculosis (TB). We describe factors associated with undiagnosed TB among HIV-infected patients attending an HIV clinic in South Africa and discuss implications for the 3 Is. DESIGN/METHODS:Convenience sample of HIV clinic attendees. METHODS:HIV-infected participants were assessed for TB using a symptom screen, sputum-smear microscopy, sputum and blood mycobacterial culture, fine needle aspiration of enlarged lymph nodes, and chest radiography. RESULTS:Four hundred twenty-two participants were enrolled. The median age and CD4+ T-cell count were 37 years [interquartile range (IQR): 31-44 years] and 215 cells per microliter (IQR: 107-347 cells/μL). Forty-seven percent had been on ART for a median duration of 8 months (IQR: 3.3-22.8 months). Three hundred sixty-one participants (85.6%) reported TB symptoms. Twenty-seven participants (6.4%) met criteria for bacteriologically confirmed TB and 50 (11.6%) for any form of TB. Bacteriologically confirmed TB was associated with CD4+ T-cell counts ≤100 cells per microliter (odds ratio: 5.05, 95% confidence interval: 1.69 to 15.12) when compared with CD4+ T-cell counts >200 cells per microliter and hemoglobin {hemoglobin < 10 g/dL [odds ratio 3.12 (95% confidence interval: 1.26 to 7.72)]}. CONCLUSIONS:Undiagnosed TB among HIV-infected ambulatory patients was associated with low CD4+ T-cell counts regardless of ART status. TB screening algorithms which include CD4+ T-cell count and hemoglobin testing may be an effective way to identify HIV-infected clinic attendees at highest risk of undiagnosed TB. Isoniazid preventive therapy and TB infection control are essential for reducing occurrence of HIV-associated TB even after ART initiation.

OBJECTIVE:To assess the diagnostic accuracy of the urine lipoarabinomannan (LAM) test among ambulatory HIV-infected persons. DESIGN/METHODS:Cross-sectional. METHODS:HIV-infected persons consecutively presenting to the HIV Clinic at Tembisa Main Clinic in Ekhuruleni, South Africa, were screened for symptoms of tuberculosis (TB) and asked to provide sputum and blood samples for smears for acid-fast bacilli and mycobacterial culture and a urine specimen for a LAM enzyme-linked immunosorbent assay. Fine needle aspirates were obtained from participants with enlarged lymph nodes and sent for histopathology. Nonpregnant participants underwent chest x-ray. RESULTS:: Four hundred twenty-two HIV-infected participants were enrolled with median age 37 years (interquartile range: 31-44 years), median CD4+ T-cell count 215 cells per microliter (interquartile range: 107-347 cells/μL), and 212 (50%) receiving antiretroviral therapy. Thirty (7%) had active TB: 18 with only pulmonary TB, 5 with only extrapulmonary TB, and 7 with both pulmonary TB and extrapulmonary TB. Twenty-seven percent [95% confidence interval (CI): 12% to 48%] of TB cases were sputum acid-fast bacilli positive. The sensitivity and specificity of the urine LAM compared with the gold standard of positive bacteriology or histopathology were 32% (95% CI: 16% to 52%) and 98% (95% CI: 96% to 99%), respectively. Urine LAM had higher sensitivity in TB cases with higher bacillary burdens, though these differences were not statistically significant. CONCLUSIONS:The sensitivity of urine LAM testing is inadequate to replace mycobacterial culture. In contrast to prior research on the urine LAM, this study was conducted among less sick, ambulatory HIV-infected patients presenting for routine care.

BACKGROUND:Human immunodeficiency virus (HIV) and tuberculosis (TB) are among the leading causes of death among women of reproductive age worldwide. TB is a significant cause of maternal morbidity. Detection of TB during pregnancy could provide substantial benefits to women and their children. METHODS:This was a cross-sectional implementation research study of integrating active TB case-finding into existing antenatal and prevention of mother-to-child transmission services in six clinics in Soweto, South Africa. All pregnant women 18 years of age or older presenting for routine care to these public clinics were screened for symptoms of active TB, cough for 2 weeks or longer, sputum production, fevers, night sweats, or weight loss, regardless of their HIV status. Participants with any symptom of active TB were asked to provide a sputum specimen for smear microscopy, mycobacterial culture and drug-susceptibility testing. RESULTS:Between December 2008 and July 2009, 3963 pregnant women were enrolled and screened for TB, of whom 1454 (36.7%) were HIV-seropositive. Any symptom of TB was reported by 23.1% of HIV-seropositive and 13.8% of HIV-seronegative women (P < 0.01). Active pulmonary TB was diagnosed in 10 of 1454 HIV-seropositve women (688 per 100,000) and 5 of 2483 HIV-seronegative women (201 per 100,000, P = 0.03). The median CD4⁺ T-cell count among HIV-seropositive women with TB was similar to that of HIV-seropositive women without TB (352 versus 333 cells/μL, P = 0.85). CONCLUSIONS:There is a high burden of active TB among HIV-seropositive pregnant women. TB screening and provision of isoniazid preventive therapy and antiretroviral therapy should be integrated with prevention of mother-to-child transmission services.

OBJECTIVES/OBJECTIVE:To assess adherence to a 1996 health policy change, which discontinued mandatory tuberculin skin testing (TST) of new entrants to NYC primary schools and continued mandatory testing of new entrants to secondary schools. METHODS:The proportion tested before (1991-1995) and after (1996-1998) the change in health policy was determined. Factors associated with TST positivity and the cost of continued testing were assessed. RESULTS:A total of 76.6% of 551 636 new entrants to primary schools were tested in 1991-1995; slightly fewer, 71.1% of 339 958, were tested in 1996- 1998. Among new entrants to secondary schools, 31.0% of 106 463 were tested in 1991-1995 and 51.4% of 53 762 were tested in 1996-1998. The proportion who were TST-positive continued to decrease after 1996 to 1.2% among primary and 9.7% among secondary schoolchildren in 1998. Older age and birth outside the United States were associated with TST positivity. The estimated minimum cost of continued testing in primary schools was $123 152 per tuberculosis case prevented. CONCLUSION/CONCLUSIONS:An approach aimed at reducing testing of children at low risk for latent tuberculosis infection did not decrease testing of younger children. More important, older children who were more likely to be born in countries of high tuberculosis incidence were not tested. Additional efforts are needed to increase awareness among medical and school personnel to decrease testing among children who do not have risk factors for latent tuberculosis infection and to increase tuberculin testing of children who are entering school for the first time at the secondary level and do have risk factors for tuberculosis infection.

Rapid diagnostic tests for tuberculosis (TB) are needed to facilitate early treatment of TB and prevention of Mycobacterium tuberculosis transmission. The ICT Tuberculosis test is a rapid, card-based immunochromatographic test for detection of antibodies directed against M. tuberculosis antigens. The objective of the study was to evaluate the performance of the ICT Tuberculosis test for the diagnosis of active pulmonary TB (PTB) with whole blood, plasma, and serum from patients suspected of having PTB and from asymptomatic controls in a setting with a high prevalence of PTB. Seventy patients suspected of having PTB (and who were later confirmed to have or not to have PTB by use of M. tuberculosis culture as the "gold standard") and 42 controls were studied. Twenty-one controls were neither vaccinated with Mycobacterium bovis bacillus Calmette-Guérin (BCG) nor tuberculin skin test (TST) positive (group A controls), and 21 controls were TST positive and/or had previously been vaccinated with BCG (group B controls). Study subjects were drawn from one hospital and one primary health care unit in Rio de Janeiro City, Brazil. One version of the test (ICT-1) was evaluated by using whole blood, plasma, and serum samples. Sera obtained for this study were frozen and later tested with a manufacturer-modified version of the test (ICT-2). Among the patients suspected of having PTB, the sensitivities of the ICT-1 with whole blood, serum, and plasma were 83, 65, and 70%, respectively, and the specificities were 46, 67, and 56%, respectively. Among the group A controls, the specificities of ICT-1 with the three specimen types were 95, 100, and 95%, respectively. Among the group B controls, the specificities of ICT-1 with the three specimen types were 71, 86, and 86%, respectively. Among the patients suspected of having PTB, the sensitivity of ICT-2 was 70% and the specificity was 65%. Among the group A controls, the specificity of ICT-2 was 95%, and among the group B controls, the specificity of ICT-2 was 81%. With a 29% observed prevalence of PTB among patients suspected of having PTB, the positive predictive values of the ICT tests ranged from 39 to 50% and the negative predictive values ranged from 82 to 87%. The ICT Tuberculosis tests were not sufficiently predictive to warrant their widespread use as routine diagnostic tests for PTB in this setting. However, further evaluation of these tests in specific epidemiologic settings may be warranted.