Preventing tuberculosis among HIV-infected pregnant women in Lesotho: the case for rolling out active case finding and isoniazid preventive therapy.

BACKGROUND: The Lesotho Ministry of Health issued guidelines on active case finding (ACF) for tuberculosis (TB) and isoniazid preventive therapy (IPT) in April 2011. ACF has been recommended in maternal and child health (MCH) settings globally, however, the feasibility of implementing IPT within MCH in countries with high concurrent HIV and TB epidemics is unknown. DESIGN/METHODS: The study evaluated the implementation of ACF and IPT guidelines in MCH settings in 2 health facilities in Lesotho. This descriptive prospective study analyzed data collected during routine services. Categorical data and continuous variables were summarized using descriptive statistics. The χ test or Wilcoxon rank-sum test was used to ascertain significant associations between categorical and continuous variables, respectively. RESULTS: Data from 160 HIV-positive and 640 HIV-negative women were reviewed. Within this study population, 99.8% of women were screened for TB, and 11.4% HIV-positive women compared with 2.3% HIV-negative women were reported to have symptoms of TB (P < 0.001). IPT was initiated in 124/158 (78.5%) HIV-positive pregnant women, 64.5% women completed a 6-month IPT regimen, 2 (1.6%) died of causes unrelated to IPT/TB, and 31.5% were lost to follow-up. Predictors of IPT initiation among HIV-positive women included gestational age at the first antenatal visit (unadjusted odds ratio, -0.93; 95% confidence interval: -0.88 to 0.98), and receipt of antiretroviral therapy for treatment rather than for prevention of mother-to-child transmission prophylaxis only (odds ratio, 4.59; 95% confidence interval: 1.32 to 15.93). CONCLUSIONS: Implementation of ACF and IPT is feasible within the MCH setting. Uptake of IPT during pregnancy among HIV-positive women was high, but with a high rate of loss to follow-up.

Gender-related barriers and delays in accessing tuberculosis diagnostic and treatment services: a systematic review of qualitative studies.

Background. Tuberculosis (TB) remains a significant global public health problem with known gender-related (male versus female) disparities. We reviewed the qualitative evidence (written/spoken narrative) for gender-related differences limiting TB service access from symptom onset to treatment initiation. Methods. Following a systematic process, we searched 12 electronic databases, included qualitative studies that assessed gender differences in accessing TB diagnostic and treatment services, abstracted data, and assessed study validity. Using a modified "inductive coding" system, we synthesized emergent themes within defined barriers and delays limiting access at the individual and provider/system levels and examined gender-related differences. Results. Among 13,448 studies, 28 studies were included. All were conducted in developing countries and assessed individual-level barriers; 11 (39%) assessed provider/system-level barriers, 18 (64%) surveyed persons with suspected or diagnosed TB, and 7 (25%) exclusively surveyed randomly sampled community members or health care workers. Each barrier affected both genders but had gender-variable nature and impact reflecting sociodemographic themes. Women experienced financial and physical dependence, lower general literacy, and household stigma, whereas men faced work-related financial and physical barriers and community-based stigma. Conclusions. In developing countries, barriers limiting access to TB care have context-specific gender-related differences that can inform integrated interventions to optimize TB services.

Barriers and delays in tuberculosis diagnosis and treatment services: does gender matter?

Background. Tuberculosis (TB) remains a global public health problem with known gender-related disparities. We reviewed the quantitative evidence for gender-related differences in accessing TB services from symptom onset to treatment initiation. Methods. Following a systematic review process, we: searched 12 electronic databases; included quantitative studies assessing gender differences in accessing TB diagnostic and treatment services; abstracted data; and assessed study validity. We defined barriers and delays at the individual and provider/system levels using a conceptual framework of the TB care continuum and examined gender-related differences. Results. Among 13,448 articles, 137 were included: many assessed individual-level barriers (52%) and delays (42%), 76% surveyed persons presenting for care with diagnosed or suspected TB, 24% surveyed community members, and two-thirds were from African and Asian regions. Many studies reported no gender differences. Among studies reporting disparities, women faced greater barriers (financial: 64% versus 36%; physical: 100% versus 0%; stigma: 85% versus 15%; health literacy: 67% versus 33%; and provider-/system-level: 100% versus 0%) and longer delays (presentation to diagnosis: 45% versus 0%) than men. Conclusions. Many studies found no quantitative gender-related differences in barriers and delays limiting access to TB services. When differences were identified, women experienced greater barriers and longer delays than men.

The ethics of testing a test: randomized trials of the health impact of diagnostic tests for infectious diseases.

In the last decade, many new rapid diagnostic tests for infectious diseases have been developed. In general, these new tests are developed with the intent to optimize feasibility and population health, not accuracy alone. However, unlike drugs or vaccines, diagnostic tests are evaluated and licensed on the basis of accuracy, not health impact (eg, reduced morbidity or mortality). Thus, these tests are sometimes recommended or scaled up for purposes of improving population health without randomized evidence that they do so. We highlight the importance of randomized trials to evaluate the health impact of novel diagnostics and note that such trials raise distinctive ethical challenges of equipoise, equity, and informed consent. We discuss the distinction between equipoise for patient-important outcomes versus diagnostic accuracy, the equity implications of evaluating health impact of diagnostics under routine conditions, and the importance of offering reasonable choices for informed consent in diagnostic trials.

Undiagnosed tuberculosis among HIV clinic attendees: association with antiretroviral therapy and implications for intensified case finding, isoniazid preventive therapy, and infection control.

OBJECTIVES: 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: 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.

Diagnostic accuracy of a urine lipoarabinomannan enzyme-linked immunosorbent assay for screening ambulatory HIV-infected persons for tuberculosis.

OBJECTIVE: To assess the diagnostic accuracy of the urine lipoarabinomannan (LAM) test among ambulatory HIV-infected persons. DESIGN: 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.

Active tuberculosis case-finding among pregnant women presenting to antenatal clinics in Soweto, South Africa.

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.

Tuberculin testing and risk of tuberculosis infection among New York City schoolchildren.

OBJECTIVES: 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: 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.