Tuberculosis among Newly Arrived Immigrants and Refugees in the United States.

Rationale: U.S. health departments routinely conduct post-arrival evaluation of immigrants and refugees at risk for tuberculosis (TB), but this important intervention has not been thoroughly studied.Objectives: To assess outcomes of the post-arrival evaluation intervention.Methods: We categorized at-risk immigrants and refugees as having had recent completion of treatment for pulmonary TB disease overseas (including in Mexico and Canada); as having suspected TB disease (chest radiograph/clinical symptoms suggestive of TB) but negative culture results overseas; or as having latent TB infection (LTBI) diagnosed overseas. Among 2.1 million U.S.-bound immigrants and refugees screened for TB overseas during 2013-2016, 90,737 were identified as at risk for TB. We analyzed a national data set of these at-risk immigrants and refugees and calculated rates of TB disease for those who completed post-arrival evaluation.Results: Among 4,225 persons with recent completion of treatment for pulmonary TB disease overseas, 3,005 (71.1%) completed post-arrival evaluation within 1 year of arrival; of these, TB disease was diagnosed in 22 (732 cases/100,000 persons), including 4 sputum culture-positive cases (133 cases/100,000 persons), 13 sputum culture-negative cases (433 cases/100,000 persons), and 5 cases with no reported sputum-culture results (166 cases/100,000 persons). Among 55,938 with suspected TB disease but negative culture results overseas, 37,089 (66.3%) completed post-arrival evaluation; of these, TB disease was diagnosed in 597 (1,610 cases/100,000 persons), including 262 sputum culture-positive cases (706 cases/100,000 persons), 281 sputum culture-negative cases (758 cases/100,000 persons), and 54 cases with no reported sputum-culture results (146 cases/100,000 persons). Among 30,574 with LTBI diagnosed overseas, 18,466 (60.4%) completed post-arrival evaluation; of these, TB disease was diagnosed in 48 (260 cases/100,000 persons), including 11 sputum culture-positive cases (60 cases/100,000 persons), 22 sputum culture-negative cases (119 cases/100,000 persons), and 15 cases with no reported sputum-culture results (81 cases/100,000 persons). Of 21,714 persons for whom treatment for LTBI was recommended at post-arrival evaluation, 14,977 (69.0%) initiated treatment and 8,695 (40.0%) completed treatment.Conclusions: Post-arrival evaluation of at-risk immigrants and refugees can be highly effective. To optimize the yield and impact of this intervention, strategies are needed to improve completion rates of post-arrival evaluation and treatment for LTBI.

The Predictive Performance of a Pneumonia Severity Score in Human Immunodeficiency Virus-negative Children Presenting to Hospital in 7 Low- and Middle-income Countries.

BACKGROUND: In 2015, pneumonia remained the leading cause of mortality in children aged 1-59 months. METHODS: Data from 1802 human immunodeficiency virus (HIV)-negative children aged 1-59 months enrolled in the Pneumonia Etiology Research for Child Health (PERCH) study with severe or very severe pneumonia during 2011-2014 were used to build a parsimonious multivariable model predicting mortality using backwards stepwise logistic regression. The PERCH severity score, derived from model coefficients, was validated on a second, temporally discrete dataset of a further 1819 cases and compared to other available scores using the C statistic. RESULTS: Predictors of mortality, across 7 low- and middle-income countries, were age <1 year, female sex, ≥3 days of illness prior to presentation to hospital, low weight for height, unresponsiveness, deep breathing, hypoxemia, grunting, and the absence of cough. The model discriminated well between those who died and those who survived (C statistic = 0.84), but the predictive capacity of the PERCH 5-stratum score derived from the coefficients was moderate (C statistic = 0.76). The performance of the Respiratory Index of Severity in Children score was similar (C statistic = 0.76). The number of World Health Organization (WHO) danger signs demonstrated the highest discrimination (C statistic = 0.82; 1.5% died if no danger signs, 10% if 1 danger sign, and 33% if ≥2 danger signs). CONCLUSIONS: The PERCH severity score could be used to interpret geographic variations in pneumonia mortality and etiology. The number of WHO danger signs on presentation to hospital could be the most useful of the currently available tools to aid clinical management of pneumonia.

Incidence and etiology of acute lower respiratory tract infections in hospitalized children younger than 5 years in rural Thailand.

BACKGROUND: Pneumonia remains a leading cause of under-five morbidity and mortality globally. Comprehensive incidence, epidemiologic and etiologic data are needed to update prevention and control strategies. METHODS: We conducted active, population-based surveillance for hospitalized cases of acute lower respiratory tract infections (ALRI) among children <5 years of age in rural Thailand. ALRI cases were systematically sampled for an etiology study that tested nasopharyngeal specimens by polymerase chain reaction; children without ALRI were enrolled as controls from outpatient clinics. RESULTS: We identified 28,543 hospitalized ALRI cases from 2005 to 2010. Among the 49% with chest radiographs, 76% had findings consistent with pneumonia as identified by 2 study radiologists. The hospitalized ALRI incidence rate was 5772 per 100,000 child-years (95% confidence interval: 5707, 5837) and was higher in boys versus girls (incidence rate ratio 1.38, 95% confidence interval: 1.35-1.41) and in children 6-23 months of age versus other age groups (incidence rate ratio 1.76, 95% confidence interval: 1.69-1.84). Viruses most commonly detected in ALRI cases were respiratory syncytial virus (19.5%), rhinoviruses (18.7%), bocavirus (12.8%) and influenza viruses (8%). Compared with controls, ALRI cases were more likely to test positive for respiratory syncytial virus, influenza, adenovirus, human metapneumovirus and parainfluenza viruses 1 and 3 (P ≤ 0.01 for all). Bloodstream infections, most commonly Streptococcus pneumoniae and nontyphoidal Salmonella, accounted for 1.8% of cases. CONCLUSIONS: Our findings underscore the high burden of hospitalization for ALRI and the importance of viral pathogens among children in Thailand. Interventions targeting viral pathogens coupled with improved diagnostic approaches, especially for bacteria, are critical for better understanding of ALRI etiology, prevention and control.

Estimating the impact of newly arrived foreign-born persons on tuberculosis in the United States.

BACKGROUND: Among approximately 163.5 million foreign-born persons admitted to the United States annually, only 500,000 immigrants and refugees are required to undergo overseas tuberculosis (TB) screening. It is unclear what extent of the unscreened nonimmigrant visitors contributes to the burden of foreign-born TB in the United States. METHODOLOGY/PRINCIPAL FINDINGS: We defined foreign-born persons within 1 year after arrival in the United States as "newly arrived", and utilized data from U.S. Department of Homeland Security, U.S. Centers for Disease Control and Prevention, and World Health Organization to estimate the incidence of TB among newly arrived foreign-born persons in the United States. During 2001 through 2008, 11,500 TB incident cases, including 291 multidrug-resistant TB incident cases, were estimated to occur among 20,989,738 person-years for the 1,479,542,654 newly arrived foreign-born persons in the United States. Of the 11,500 estimated TB incident cases, 41.6% (4,783) occurred among immigrants and refugees, 36.6% (4,211) among students/exchange visitors and temporary workers, 13.8% (1,589) among tourists and business travelers, and 7.3% (834) among Canadian and Mexican nonimmigrant visitors without an I-94 form (e.g., arrival-departure record). The top 3 newly arrived foreign-born populations with the largest estimated TB incident cases per 100,000 admissions were immigrants and refugees from high-incidence countries (e.g., 2008 WHO-estimated TB incidence rate of ≥100 cases/100,000 population/year; 235.8 cases/100,000 admissions, 95% confidence interval [CI], 228.3 to 243.3), students/exchange visitors and temporary workers from high-incidence countries (60.9 cases/100,000 admissions, 95% CI, 58.5 to 63.3), and immigrants and refugees from medium-incidence countries (e.g., 2008 WHO-estimated TB incidence rate of 15-99 cases/100,000 population/year; 55.2 cases/100,000 admissions, 95% CI, 51.6 to 58.8). CONCLUSIONS/SIGNIFICANCE: Newly arrived nonimmigrant visitors contribute substantially to the burden of foreign-born TB in the United States. To achieve the goals of TB elimination, direct investment in global TB control and strategies to target nonimmigrant visitors should be considered.

High prevalence of cryptococcal infection among HIV-infected patients hospitalized with pneumonia in Thailand.

BACKGROUND: Cryptococcal meningitis (CM) is a major cause of death among HIV-infected patients. Cryptococcal antigenemia (CrAg+) in the absence of CM can represent early-stage cryptococcosis during which antifungal treatment might improve outcomes. However, patients without meningitis are rarely tested for cryptococcal infection. We evaluated Cryptococcus species as a cause of acute respiratory infection in hospitalized patients in Thailand and evaluated clinical characteristics associated with CrAg+. METHODS: We tested banked serum samples from 704 human immunodeficiency virus (HIV)-infected and 730 HIV-uninfected patients hospitalized with acute respiratory infection from 2004 through 2009 in 2 rural provinces in Thailand for the presence of CrAg+. Retrospective chart reviews were conducted for CrAg+ patients to distinguish meningeal and nonmeningeal cryptococcosis and to identify clinical characteristics associated with CrAg+ in patients with and without evidence of CM. RESULTS: CrAg+ was found in 92 HIV-infected patients (13.1%); only tuberculosis (19.3%) and rhinovirus (16.5%) were identified more frequently. No HIV-uninfected patients were CrAg+. Of 70 CrAg+ patients with medical charts available, 37 (52.9%) had no evidence of past or existing CM at hospitalization; 30 of those patients (42.9% of all CrAg+) had neither past nor existing CM, nor any alternate etiology of infection identified. Dyspnea was more frequent among CrAg+ patients without CM than among CrAg- patients (P = .0002). CONCLUSIONS: Cryptococcus species were the most common pathogens detected in HIV-infected patients hospitalized with acute respiratory infection in Thailand. Few clinical differences were found between antigenemic and nonantigenemic HIV-infected patients. Health care providers in Thailand should evaluate HIV-infected patients hospitalized with acute respiratory infection for cryptococcal antigenemia, even in the absence of meningitis.

Overseas screening for tuberculosis in U.S.-bound immigrants and refugees.

BACKGROUND: In 2007, a total of 57.8% of the 13,293 new cases of tuberculosis in the United States were diagnosed in foreign-born persons, and the tuberculosis rate among foreign-born persons was 9.8 times as high as that among U.S.-born persons (20.6 vs. 2.1 cases per 100,000 population). Annual arrivals of approximately 400,000 immigrants and 50,000 to 70,000 refugees from overseas are likely to contribute substantially to the tuberculosis burden among foreign-born persons in the United States. METHODS: The Centers for Disease Control and Prevention (CDC) collects information on overseas screening for tuberculosis among U.S.-bound immigrants and refugees, along with follow-up evaluation after their arrival in the United States. We analyzed screening and follow-up data from the CDC to study the epidemiology of tuberculosis in these populations. RESULTS: From 1999 through 2005, a total of 26,075 smear-negative cases of tuberculosis (i.e., cases in which a chest radiograph was suggestive of active tuberculosis but sputum smears were negative for acid-fast bacilli on 3 consecutive days) and 22,716 cases of inactive tuberculosis (i.e., cases in which a chest radiograph was suggestive of tuberculosis that was no longer clinically active) were diagnosed by overseas medical screening of 2,714,223 U.S.-bound immigrants, representing prevalences of 961 cases per 100,000 persons (95% confidence interval [CI], 949 to 973) and 837 cases per 100,000 persons (95% CI, 826 to 848), respectively. Among 378,506 U.S.-bound refugees, smear-negative tuberculosis was diagnosed in 3923 and inactive tuberculosis in 10,743, representing prevalences of 1036 cases per 100,000 persons (95% CI, 1004 to 1068) and 2838 cases per 100,000 persons (95% CI, 2785 to 2891), respectively. Active pulmonary tuberculosis was diagnosed in the United States in 7.0% of immigrants and refugees with an overseas diagnosis of smear-negative tuberculosis and in 1.6% of those with an overseas diagnosis of inactive tuberculosis. CONCLUSIONS: Overseas screening for tuberculosis with follow-up evaluation after arrival in the United States is a high-yield intervention for identifying tuberculosis in U.S.-bound immigrants and refugees and could reduce the number of tuberculosis cases among foreign-born persons in the United States.

Multidrug-resistant tuberculosis outbreak among US-bound Hmong refugees, Thailand, 2005.

In January 2005, tuberculosis (TB), including multidrug-resistant TB (MDR TB), was reported among Hmong refugees who were living in or had recently immigrated to the United States from a camp in Thailand. We investigated TB and drug resistance, enhanced TB screenings, and expanded treatment capacity in the camp. In February 2005, 272 patients with TB (24 MDR TB) remained in the camp. Among 17 MDR TB patients interviewed, 13 were found to be linked socially. Of 23 MDR TB isolates genotyped, 20 were similar according to 3 molecular typing methods. Before enhanced screening was implemented, 46 TB cases (6 MDR TB) were diagnosed in the United States among 9,455 resettled refugees. After enhanced screening had begun, only 4 TB cases (1 MDR TB), were found among 5,705 resettled refugees. An MDR TB outbreak among US-bound refugees led to importation of disease; enhanced pre-immigration TB screening and treatment decreased subsequent importation.

Assessing the performance of overseas tuberculosis screening programs: a study among US-bound immigrants in Vietnam.

BACKGROUND: Tuberculosis cases in foreign-born persons account for more than 50% of all tuberculosis cases in the United States. The Institute of Medicine has recommended enhancing overseas screening as one measure to support tuberculosis elimination efforts. We assessed the ability of overseas tuberculosis screening (chest radiograph followed by 3 acid-fast bacilli sputum smears for persons with abnormal chest radiographs [suggestive of active tuberculosis]) to detect pulmonary tuberculosis disease among US-bound immigrants with abnormal chest radiographs. METHODS: During October 1998 to October 1999, 14 098 US immigrant visa applicants were screened overseas in Vietnam. Adult applicants with abnormal chest radiographs were enrolled to assess screening test characteristics among this group using mycobacterial culture as the gold standard for pulmonary tuberculosis disease diagnosis. Risk factors for pulmonary tuberculosis disease were also evaluated. RESULTS: Among 1179 adult applicants with abnormal chest radiographs, 82 (7.0%) had positive acid-fast bacilli smear results, and 183 (15.5%) had positive Mycobacterium tuberculosis culture results (pulmonary tuberculosis disease). The sensitivity, specificity, and positive and negative predictive values of serial acid-fast bacilli screening among this group were 34.4% (63/183), 98.1% (977/996), 76.8% (63/82), and 89.1% (977/1097), respectively. Risk factors for pulmonary tuberculosis disease included younger age (18-34 years), no history of tuberculosis or treatment, reported symptoms, and cavitation or consolidation on chest radiograph. CONCLUSIONS: The ability of current overseas screening to detect tuberculosis among immigrants with abnormal chest radiographs is low. Improved diagnostic methods, enhanced screening measures, and postmigration follow-up are essential to control tuberculosis among immigrants and support US and global tuberculosis elimination.