Carla A. Winston

Tuberculosis Among Foreign-Born Persons in the United States

CONTEXT Foreign-born persons accounted for 57% of all tuberculosis (TB) cases in the United States in 2006. Current TB control strategies have not sufficiently addressed the high levels of TB disease and latent TB infection in this population. OBJECTIVE To determine the risk of TB disease and drug-resistant TB among foreign-born populations and the potential impact of adding TB culture to overseas screening procedures for foreign-born persons entering the United States. DESIGN, SETTING, AND PARTICIPANTS Descriptive epidemiologic analysis of foreign-born persons in the United States diagnosed with TB from 2001 through 2006. MAIN OUTCOME MEASURES TB case rates, stratified by time since US entry, country of origin, and age at US entry; anti-TB drug-resistance patterns; and characteristics of TB cases diagnosed within 3 months of US entry. RESULTS A total of 46,970 cases of TB disease were reported among foreign-born persons in the United States from 2001 through 2006, of which 12,928 (28%) were among recent entrants (within 2 years of US entry). Among the foreign-born population overall, TB case rates declined with increasing time since US entry, but remained higher than among US-born persons--even more than 20 years after arrival. In total, 53% of TB cases among foreign-born persons occurred among the 22% of the foreign-born population born in sub-Saharan Africa and Southeast Asia. Isoniazid resistance was as high as 20% among recent entrants from Vietnam and 18% for recent entrants from Peru. On average, 250 individuals per year were diagnosed with smear-negative, culture-positive TB disease within 3 months of US entry; 46% of these were from the Philippines or Vietnam. CONCLUSION The relative yield of finding and treating latent TB infection is particularly high among individuals from most countries of sub-Saharan Africa and Southeast Asia.

Isoniazid, Rifampin, Ethambutol, and Pyrazinamide Pharmacokinetics and Treatment Outcomes Among a Predominantly HIV-Infected Cohort of Adults with Tuberculosis from Botswana

BACKGROUND We explored the association between antituberculosis drug pharmacokinetics and treatment outcomes among patients with pulmonary tuberculosis in Botswana. METHODS Consenting outpatients with tuberculosis had blood samples collected 1, 2, and 6 h after simultaneous isoniazid, rifampin, ethambutol, and pyrazinamide ingestion. Maximum serum concentrations (C(max)) and areas under the serum concentration time curve were determined. Clinical status was monitored throughout treatment. RESULTS Of the 225 participants, 36 (16%) experienced poor treatment outcome (treatment failure or death); 155 (69%) were infected with human immunodeficiency virus (HIV). Compared with published standards, low isoniazid C(max) occurred in 84 patients (37%), low rifampin C(max) in 188 (84%), low ethambutol C(max) in 87 (39%), and low pyrazinamide C(max) in 11 (5%). Median rifampin and pyrazinamide levels differed significantly by HIV status and CD4 cell count category. Only pyrazinamide pharmacokinetics were significantly associated with treatment outcome; low pyrazinamide C(max) was associated with a higher risk of documented poor treatment outcome, compared with normal C(max) (50% vs. 16%; P < .01). HIV-infected patients with a CD4 cell count <200 cells/microL had a higher risk of poor treatment outcome (27%) than did HIV-uninfected patients (11%) or HIV-infected patients with a CD4 cell count 200 cells/microL (12%; P = .01). After adjustment for HIV infection and CD4 cell count, patients with low pyrazinamide C(max) were 3 times more likely than patients with normal pyrazinamide C(max) to have poor outcomes (adjusted risk ratio, 3.38; 95% confidence interval, 1.84-6.22). CONCLUSIONS Lower than expected antituberculosis drug C(max) occurred frequently, and low pyrazinamide C(max) was associated with poor treatment outcome. Exploring the global prevalence and significance of these findings may suggest modifications in treatment regimens that could improve tuberculosis cure rates.

Factors associated with vaccination of medicare beneficiaries in five U.S. communities: Results from the racial and ethnic adult disparities in immunization initiative survey, 2003.

OBJECTIVES: To examine vaccination in seniors in the five U.S. communities of the Racial and Ethnic Adult Disparities in Immunization Initiative.

Relationship Between Mycobacterium tuberculosis Phylogenetic Lineage and Clinical Site of Tuberculosis

BACKGROUND Genotyping of Mycobacterium tuberculosis has revealed 4 major phylogenetic lineages with differential distribution worldwide. It is not clear whether different lineages are associated with different sites of infection (eg, pulmonary tuberculosis versus extrapulmonary tuberculosis). We sought to determine whether M. tuberculosis lineage is associated with the site of tuberculosis disease. METHODS We conducted a cross-sectional analysis of all culture-confirmed cases of tuberculosis with routinely determined M. tuberculosis spoligotype-defined lineage reported to the US National Tuberculosis Surveillance System from 2004 through 2008. Odds ratios (ORs) were used to assess the relation between disease site and M. tuberculosis lineage, after adjustment for age, sex, human immunodeficiency virus infection status, region of birth, and race/ethnicity. RESULTS Of 53972 reported culture-positive tuberculosis cases, 32000 (59.3%) were cases of M. tuberculosis that included complete spoligotype-based data on lineage. Of these, 23844 (74.5%) were exclusively pulmonary, 5085 (15.9%) were exclusively extrapulmonary, and 3071 (9.6%) were combined pulmonary and extrapulmonary. The percentages of tuberculosis cases that were exclusively extrapulmonary differed by lineage: East Asian, 13.0%; Euro-American, 13.8%; Indo-Oceanic, 22.6%; and East-African Indian, 34.3%. Compared with East Asian lineage, the odds of exclusively extrapulmonary tuberculosis relative to exclusively pulmonary tuberculosis were greater for Euro-American (adjusted OR, 1.3; 95% confidence interval [CI], 1.1-1.4), Indo-Oceanic (adjusted OR, 1.7; 95% CI, 1.5-1.9), and East-African Indian (adjusted OR, 1.6; 95% CI, 1.4-1.9) lineages. CONCLUSIONS Phylogenetic lineage of M. tuberculosis is associated with the site of tuberculosis disease.

Pediatric and Adolescent Tuberculosis in the United States, 2008–2010

OBJECTIVE: We examined heterogeneity among children and adolescents diagnosed with tuberculosis (TB) in the United States, and we investigated potential international TB exposure risk. METHODS: We analyzed demographic and clinical characteristics by origin of birth for persons <18 years with verified case of incident TB disease reported to National TB Surveillance System from 2008 to 2010. We describe newly available data on parent or guardian countries of origin and history of having lived internationally for pediatric patients with TB (<15 years of age). RESULTS: Of 2660 children and adolescents diagnosed with TB during 2008–2010, 822 (31%) were foreign-born; Mexico was the most frequently reported country of foreign birth. Over half (52%) of foreign-born patients diagnosed with TB were adolescents aged 13 to 17 years who had lived in the United States on average >3 years before TB diagnosis. Foreign-born pediatric patients with foreign-born parents were older (mean, 7.8 years) than foreign-born patients with US-born parents (4.2 years) or US-born patients (3.6 years). Among US-born pediatric patients, 66% had at least 1 foreign-born parent, which is >3 times the proportion in the general population. Only 25% of pediatric patients with TB diagnosed in the United States had no known international connection through family or residence history. CONCLUSIONS: Three-quarters of pediatric patients with TB in the United States have potential TB exposures through foreign-born parents or residence outside the United States. Missed opportunities to prevent TB disease may occur if clinicians fail to assess all potential TB exposures during routine clinic visits.

Estimated Rate of Reactivation of Latent Tuberculosis Infection in the United States, Overall and by Population Subgroup

We estimated the rate of reactivation tuberculosis (TB) in the United States, overall and by population subgroup, using data on TB cases and Mycobacterium tuberculosis isolate genotyping reported to the Centers for Disease Control and Prevention during 2006-2008. The rate of reactivation TB was defined as the number of non-genotypically clustered TB cases divided by the number of person-years at risk for reactivation due to prevalent latent TB infection (LTBI). LTBI was ascertained from tuberculin skin tests given during the 1999-2000 National Health and Nutrition Examination Survey. Clustering of TB cases was determined using TB genotyping data collected by the Centers for Disease Control and Prevention and analyzed via spatial scan statistic. Of the 39,920 TB cases reported during 2006-2008, 79.7% were attributed to reactivation. The overall rate of reactivation TB among persons with LTBI was estimated as 0.084 (95% confidence interval (CI): 0.083, 0.085) cases per 100 person-years. Rates among persons with and without human immunodeficiency virus coinfection were 1.82 (95% CI: 1.74, 1.89) and 0.073 (95% CI: 0.070, 0.075) cases per 100 person-years, respectively. The rate of reactivation TB among persons with LTBI was higher among foreign-born persons (0.098 cases/100 person-years; 95% CI: 0.096, 0.10) than among persons born in the United States (0.082 cases/100 person-years; 95% CI: 0.080, 0.083). Differences in rates of TB reactivation across subgroups support current recommendations for targeted testing and treatment of LTBI.

Seasonality of Tuberculosis in the United States, 1993–2008

BACKGROUND Although seasonal variation in tuberculosis incidence has been described in several recent studies, the mechanism underlying this seasonality remains unknown. Seasonality of tuberculosis disease may indicate the presence of season-specific risk factors that could potentially be controlled if they were better understood. We conducted this study to determine whether tuberculosis is seasonal in the United States and to describe patterns of seasonality in specific populations. METHODS We performed a time series decomposition analysis of tuberculosis cases reported to the Centers for Disease Control and Prevention from 1993 through 2008. Seasonal amplitude of tuberculosis disease (the difference between the months with the highest and lowest mean case counts), was calculated for the population as a whole and for populations with select demographic, clinical, and epidemiologic characteristics. RESULTS A total of 243 432 laboratory-confirmed tuberculosis cases were reported over a period of 16 years. A mean of 21.4% more cases were diagnosed in March, the peak month, compared with November, the trough month. The magnitude of seasonality did not vary with latitude. The greatest seasonal amplitude was found among children aged <5 years and in cases associated with disease clusters. CONCLUSIONS Tuberculosis is a seasonal disease in the United States, with a peak in spring and trough in late fall. The latitude independence of seasonality suggests that reduced winter sunlight exposure may not be a strong contributor to tuberculosis risk. Increased seasonality among young children and clustered cases suggests that disease that is the result of recent transmission is more influenced by season than disease resulting from activation of latent infection.

Viewpoint: evaluating the impact of malaria control efforts on mortality in sub-Saharan Africa.

Objective  To describe an approach for evaluating the impact of malaria control efforts on malaria‐associated mortality in sub‐Saharan Africa, where disease‐specific mortality trends usually cannot be measured directly and most malaria deaths occur among young children.

Epidemiology of Tuberculosis Among US- and Foreign-Born Children and Adolescents in the United States, 1994–2007

OBJECTIVES We examined trends in tuberculosis (TB) cases and case rates among US- and foreign-born children and adolescents and analyzed the potential effect of changes to overseas screening of applicants for immigration to the United States. METHODS We analyzed TB case data from the National Tuberculosis Surveillance System for 1994 to 2007. RESULTS Foreign-born children and adolescents accounted for 31% of 18,659 reported TB cases in persons younger than age 18 years from 1994 to 2007. TB rates declined 44% among foreign-born children and adolescents (20.3 per 10,000 to 11.4 per 100,000 population) and 48% (2.1 per 100,000 to 1.1 per 100,000) among those who were born in the United States. Rates were nearly 20 times as high among foreign-born as among US-born adolescents. Among foreign-born children and adolescents with known month of US entry (88%), more than 20% were diagnosed with TB within 3 months of entry. CONCLUSIONS Marked disparities in TB morbidity persist between foreign- and US-born children and adolescents. These disparities and the high proportion of TB cases diagnosed shortly after US entry suggest a need for enhanced pre- and postimmigration screening.

Tuberculosis in Older Adults in the United States, 1993–2008

OBJECTIVES: To describe older adults with tuberculosis (TB) and compare demographic, diagnostic, and disease characteristics and treatment outcomes between older and younger adults with TB.