Using Reports of Latent Tuberculosis Infection Among Young Children to Identify Tuberculosis Transmission in New York City, 2006–2012

Using Reports of Latent Tuberculosis Infection Among Young Children to Identify Tuberculosis... Abstract The presence of latent tuberculosis infection (LTBI) in young children indicates recent tuberculosis (TB) transmission. We reviewed surveillance reports of children with LTBI to assess whether more follow-up is needed to prevent TB in this high-risk population. Data on all children under 5 years of age who were reported by health-care providers or laboratories to the New York City Department of Health during 2006–2012 were abstracted from the TB surveillance and case management system, and those with LTBI were identified. Potential source cases, defined as any infectious TB case diagnosed in the 2 years before a child was reported and whose residence was within 0.5 miles (0.8 km) of the child’s residence, were identified. Neighborhood risk factors for TB transmission were examined. Among 3,511 reports of children under age 5 years, 1,722 (49%) had LTBI. The children were aged 2.9 years, on average, and most (64%) had been born in the United States. A potential source case was identified for 92% of the children; 27 children lived in the same building as a TB patient. Children with potential source cases were more likely to reside in neighborhoods with high TB incidence, poverty, and population density. The high proportion of children born in the United States and the young average age of the cases imply that undetected TB transmission occurred. Monitoring reports could be used to identify places where transmission occurred, and additional investigation is needed to prevent TB disease. children, disease transmission, geographic analysis, latent tuberculosis infection, tuberculosis Identification and treatment of young children with latent tuberculosis infection (LTBI) is a priority for tuberculosis (TB) control programs and an emphasis of the recently published World Health Organization End TB Strategy (1). LTBI in young children is indicative of recent transmission of Mycobacterium tuberculosis (2). Furthermore, young children are at greater risk for rapidly progressing to active TB disease as well as developing severe forms of disease (3). Consequently, the New York City (NYC) Health Code mandates the reporting of any positive TB test result in a child under 5 years of age, in addition to children who have or are suspected to have TB disease and children identified as contacts of an infectious TB patient (4). LTBI in children under 5 years of age is reportable because these infections are considered sentinel events indicating recent transmission (2). In NYC, all children with suspected or confirmed TB disease and children who have had contact with an infectious individual are closely case-managed by the health department to ensure appropriate evaluation and adherence to treatment (e.g., patient interviews, monthly review of patient progress). However, children reported to have a positive test for TB infection are not consistently monitored. This policy of not investigating reported cases of LTBI in children under 5 years of age was established in NYC in 2000 (5). Previously, associate investigations were conducted for all children aged ≤3 years reported with LTBI to identify the infectious TB patient who was the source of infection for each child (5). The rationale behind these investigations was that young children had limited sources of exposure and were recently infected with TB (5). However, these investigations were found to require extensive resources and often yielded minimal information on source cases (6–8). For example, in NYC from January 1, 1996, through June 30, 1998, only 2 source cases were identified among the 207 children aged ≤3 years with LTBI who had an associate investigation performed (6). Consequently, active monitoring of children with LTBI ceased in NYC (5). Since that time, the rate of active TB disease has decreased nationally in the United States (9) and locally in NYC (10). Accordingly, the focus for US TB programs has started to shift from maintaining control of TB disease to finding and treating persons with LTBI toward the goal of TB elimination (11). Furthermore, global interest in LTBI has been renewed by the publication of the World Health Organization’s End TB Strategy (1), which aims to increase the number of children started on preventive treatment for LTBI. This emerging attention to LTBI offers a critical opportunity to reassess the burden and management of LTBI among high-priority populations for TB prevention and elimination, especially young children. In this investigation, we characterized young children reported with LTBI in NYC and explored novel strategies for identifying potential source cases for these children. We employed geographic analysis to find infectious TB patients who were in close physical and temporal proximity to young children with LTBI and then evaluated the risk factors for having a potential source case identified. While it is not a means to detect new TB patients as in a traditional associate or source-case investigation (12), we aimed to use readily available surveillance data to explore whether this method could uncover locations with potential TB transmission. METHODS Study population All persons reported to the NYC Department of Health and Mental Hygiene (DOHMH) Bureau of Tuberculosis Control during 2006–2012 who were under 5 years of age at the time of report were abstracted from the Bureau of Tuberculosis Control’s electronic surveillance and case management registry (Consilience Software, Inc., Austin, Texas). Among these children, we identified those with LTBI, defined as having 1) a positive result from a tuberculin skin test or a Food and Drug Administration-approved blood-based test for TB infection and 2) no signs or symptoms of TB disease, such as documentation of cough or an abnormal chest radiograph. The annual number of LTBI cases and the rate of reported LBTI per 100,000 population in children under age 5 years were calculated. All population estimates used in rate calculations were based on DOHMH population estimates that were modified from US Census Bureau intercensal estimates. Identification of potential source cases Each child with LTBI was matched to TB patients who were considered potential sources of infection (definition below). Children who were living in a health-care facility at the time of report or who had known contact with a TB patient were excluded. Children with documented interaction with a TB patient were removed under the assumption that this TB patient would have been the child’s source of LTBI. Potential source cases included patients with active TB disease in NYC who were verified by DOHMH as a TB case during 2004–2013. To capture patients most likely to be infectious, cases were limited to those aged ≥5 years who had a positive culture for M. tuberculosis complex from a respiratory specimen. Cases were also limited to those with a known address living in the community; those with only a correctional or health-care facility address were excluded. A TB patient was defined as a potential source case to a child with LTBI if 1) the patient resided less than 0.5 miles (0.8 km) from the child’s residence and 2) the child was reported to the DOHMH either during the 3-month period prior to the patient’s diagnosis (infectious period) (13) or up to 2 years after the patient’s TB diagnosis (recent transmission of M. tuberculosis (14)). The diagnosis date was defined as the date on which the patient was verified to have active TB disease, per the Centers for Disease Control and Prevention’s case definition (15). A distance of less than 0.5 miles (0.8 km) was selected on the basis of the DOHMH’s programmatic definition of a possible epidemiologic link between individuals (16). We geocoded the address of residence for both children with LTBI and potential source cases, and then matched them by geodesic distance using ArcGIS software, version 10 (Environmental Systems Research Institute, Redlands, California). Characteristics associated with potential source case identification Neighborhood characteristics Children’s neighborhoods of residence (as defined by the NYC United Hospital Fund (UHF) (17)) were categorized according to the TB incidence rate, population density (number of persons per square mile (per 1.6 km2)), and poverty level at the time of report. Based on the year of report to the DOHMH and the annual TB incidence rate within their neighborhoods, children were categorized as residing in neighborhoods with high TB incidence (neighborhood rate (10) > citywide rate (10)), medium TB incidence (citywide rate (10) ≥ neighborhood rate (10) ≥ national rate (9)), or low TB incidence (neighborhood rate (10) < national rate (9)). The population density of each child’s UHF area was calculated by dividing the annual population estimates by the UHF area (in squared miles). Neighborhood-level poverty was characterized for children as the percentage of the population in their UHF neighborhood with a household income below the poverty threshold set by the federal government. In alignment with DOHMH area-based poverty guidelines (18), 5-year American Community Survey poverty data from 2007– 2011 were used to divide UHF neighborhoods into 4 categories indicating the percentage of residents living below the federal poverty limit: low (<10%), medium (10%–19.9%), high (20%–29.9%), and very high (≥30%). Residence characteristics We also described the types of buildings where children lived, since residing in a crowded setting serves as a risk factor for exposure to TB. Every property in NYC is classified using Real Property Assessment Division codes, and we identified the code for each child’s residential building (19). Based on Real Property Assessment Division codes, children’s residence types were divided into 4 mutually exclusive groups: 1) single-family dwelling, 2) 2-family dwelling, 3) building with 6 families or less (e.g., walk-up apartment buildings), and 4) building with more than 6 families (e.g., elevator apartment buildings). These categories were defined on the basis of Real Property Assessment Division categories, which separate NYC building sizes based on the cutpoint of 6 families. Children whose codes indicated a nonresidential building were excluded from further analysis. Statistical analysis Descriptive statistics were generated to characterize the age, sex, and birthplace of the study population. We used the Cochran-Armitage trend test to investigate whether the proportion of children with a potential source case identified differed from 2006 to 2012. To identify factors associated with identification of a possible source case, we compared the year of report to the DOHMH, age at report, birthplace, residence type, neighborhood TB incidence, neighborhood population density, and neighborhood poverty level of children with at least 1 potential source-case match with those characteristics in children who had no source case identified using a modified Poisson regression model with a log-link and robust sandwich variance estimator (20). Characteristics significantly associated with having a potential source case identified were included in an adjusted modified Poisson regression model, and relative risks and 95% confidence intervals were calculated. All analyses were conducted in SAS, version 9.2 (SAS Institute, Inc., Cary, North Carolina). Data presented were obtained as part of routine TB surveillance and case management activities. Analyses were conducted for program evaluation purposes and therefore were not subject to review by the DOHMH Institutional Review Board. RESULTS Among 3,511 children under 5 years of age reported to the DOHMH during 2006–2012, 1,722 (49%) were identified as having LTBI and 1,533 (44%) were eligible for potential source case identification after excluding those who had had known contact with a TB case and those without a valid address of residence in the community (Figure 1). The number and rate of children reported with LTBI decreased steadily from 377 children in 2006 (72.5 reports per 100,000 population aged <5 years) to 128 children in 2012 (23.5 reports per 100,000 population aged <5 years). Children with LTBI had a mean age of 2.9 years at the time of first report (median age at time of first report, 3.0 years), and about half were female (53%) (Table 1). Among the 1,399 (81%) children for whom the country of birth was recorded, the majority were US-born (64%). Among the 3,511 reports of children under age 5 years from 2006–2012, there were 72 confirmed cases of TB disease in children under age 5 years. The majority of children with confirmed TB disease did not have a known link to a source case through source-case or cluster investigations (n = 47; 65%). Figure 1. View largeDownload slide Identification of children with latent tuberculosis (TB) infection among all persons under age 5 years reported to the New York City (NYC) Department of Health and Mental Hygiene Bureau of Tuberculosis Control, New York, New York, 2006–2012. Figure 1. View largeDownload slide Identification of children with latent tuberculosis (TB) infection among all persons under age 5 years reported to the New York City (NYC) Department of Health and Mental Hygiene Bureau of Tuberculosis Control, New York, New York, 2006–2012. Table 1. Demographic Characteristics of All Children Under Age 5 Years Reported to the New York City Department of Health and Mental Hygiene Bureau of Tuberculosis Control With Latent Tuberculosis Infection (n = 1,717), New York, New York, 2006–2012a Characteristic  No. of Children  %  Age at first report, yearsb  2.9 (1.3)  Sexc       Female  903  53   Male  813  47  Birthplacec       US-bornd  890  64   Foreign-born  509  36  Country of birthe       Bangladesh  68  13   China  44  9   Dominican Republic  66  13   Jamaica  19  4   Mexico  55  11   Nigeria  28  6   Pakistan  34  7   Other  195  38  Characteristic  No. of Children  %  Age at first report, yearsb  2.9 (1.3)  Sexc       Female  903  53   Male  813  47  Birthplacec       US-bornd  890  64   Foreign-born  509  36  Country of birthe       Bangladesh  68  13   China  44  9   Dominican Republic  66  13   Jamaica  19  4   Mexico  55  11   Nigeria  28  6   Pakistan  34  7   Other  195  38  a There were 5 children reported more than once with latent tuberculosis infection between 2006 and 2012. This table includes the first reported case for children reported more than 1 time between 2006 and 2012 (n = 1,717). b Values are expressed as mean (standard deviation). c Numbers may not sum to 1,717 because of missing data. d Includes children born in the United States and its territories. e Proportion calculated among children born outside of the United States (n = 509). Table 1. Demographic Characteristics of All Children Under Age 5 Years Reported to the New York City Department of Health and Mental Hygiene Bureau of Tuberculosis Control With Latent Tuberculosis Infection (n = 1,717), New York, New York, 2006–2012a Characteristic  No. of Children  %  Age at first report, yearsb  2.9 (1.3)  Sexc       Female  903  53   Male  813  47  Birthplacec       US-bornd  890  64   Foreign-born  509  36  Country of birthe       Bangladesh  68  13   China  44  9   Dominican Republic  66  13   Jamaica  19  4   Mexico  55  11   Nigeria  28  6   Pakistan  34  7   Other  195  38  Characteristic  No. of Children  %  Age at first report, yearsb  2.9 (1.3)  Sexc       Female  903  53   Male  813  47  Birthplacec       US-bornd  890  64   Foreign-born  509  36  Country of birthe       Bangladesh  68  13   China  44  9   Dominican Republic  66  13   Jamaica  19  4   Mexico  55  11   Nigeria  28  6   Pakistan  34  7   Other  195  38  a There were 5 children reported more than once with latent tuberculosis infection between 2006 and 2012. This table includes the first reported case for children reported more than 1 time between 2006 and 2012 (n = 1,717). b Values are expressed as mean (standard deviation). c Numbers may not sum to 1,717 because of missing data. d Includes children born in the United States and its territories. e Proportion calculated among children born outside of the United States (n = 509). Identification of potential source cases The 1,533 children who were eligible for potential source case identification were matched with 4,958 TB patients who met the eligibility criteria for analysis. Overall, 1,413 children with LTBI (92% of the 1,533 eligible children) matched to 3,045 patients with active TB disease (61% of the 4,958 eligible TB patients). The median number of matches per child with a match was 6 TB patients (interquartile range, 3–15), and a total of 14,066 matches were identified. There were 404 children who matched with 1–3 TB patients. The majority of these children lived in medium- or low-TB-incidence neighborhoods (277 children; 69%) and neighborhoods with fewer than 35,000 persons per square mile (256 children; 63%). On the other end of the spectrum, there were 318 children with more than 15 matches. The majority of these children lived in high-TB-incidence neighborhoods (285 children; 90%) and neighborhoods with 35,000 or more persons per square mile (183 children; 58%). We identified 29 matches between TB patients and children who lived in the same residential building. Among these 29 matches, there were 29 unique TB patients and 27 unique children with LTBI (i.e., 2 children matched with 2 different TB patients who lived in the same residential building). Of the 29 TB patients, 20 were acid-fast bacilli respiratory-smear positive (69%), and 8 showed cavities on a chest radiograph (28%). Of the 27 children, 21 had been born in the United States (78%) and 13 were ≤2 years of age at the time of report (48%). No TB patient and child with LTBI shared a last name or were known to be related. Characteristics associated with potential source-case identification The proportion of children with 1 or more potential source cases identified across the study period decreased from 95% in 2006 to 87% in 2011 (P < 0.01; Figure 2). In unadjusted analyses, almost all risk factors for exposure to or recent transmission of M. tuberculosis, including age at report, residence type, neighborhood TB incidence, neighborhood population density, and neighborhood poverty level, were associated with having a potential source case identified (Table 2). The only exceptions were birthplace and year of report. Figure 2. View largeDownload slide Number of children under age 5 years reported to the New York City Department of Health and Mental Hygiene Bureau of Tuberculosis Control with latent tuberculosis infection who had a potential source case identified by geospatial matching, New York, New York, 2006–2012. Figure 2. View largeDownload slide Number of children under age 5 years reported to the New York City Department of Health and Mental Hygiene Bureau of Tuberculosis Control with latent tuberculosis infection who had a potential source case identified by geospatial matching, New York, New York, 2006–2012. Table 2. Bivariate and Multivariate Associations Between Risk Factors for Exposure to Tuberculosis and Having at Least 1 Potential Source Case Identified Among Children Under Age 5 Years Reported to the New York City Department of Health and Mental Hygiene Bureau of Tuberculosis Control With Latent Tuberculosis Infection, New York, New York, 2006–2012a Characteristic  ≥1 Potential Source Case Identified (n = 1,413)  No Potential Source Case Identified (n = 120)  Unadjusted RR  Adjusted RR  No. of Children  %  No. of Children  %  RR  95% CI  RR  95% CI  Year reported to DOHMH                   2006  319  23  16  13  1.05  0.99, 1.12  —b     2007  257  18  13  11  1.03  0.98, 1.12  —     2008  255  18  17  14  0.98  0.97, 1.10  —     2009  191  14  23  19  0.97  0.91, 1.06  —     2010  147  10  20  17  0.96  0.89, 1.05  —     2011  135  10  20  17  1.00  0.88, 1.04  —     2012  109  8  11  9  1.00  Referent  —    Age at reporting, years                   <1  35  2  11  9  1.00  Referent  1.00  Referent   1  354  25  43  36  1.17  0.99, 1.38  1.13  0.98, 1.30   2  292  21  25  21  1.21  1.03, 1.43  1.16  1.01, 1.33   3  325  23  24  20  1.22  1.04, 1.44  1.18  1.03, 1.36   4  407  29  17  14  1.26  1.07, 1.49  1.19  1.04, 1.37  Birthplace                   US-bornc  692  49  58  48  1.00  Referent  —     Foreign-born  445  31  35  29  1.00  0.97, 1.04  —     Unknown  276  20  27  23  0.99  0.95, 1.03  —    Residence typed                   1-family dwelling  71  5  22  19  1.00  Referent  1.00  Referent   2-family dwelling  304  22  33  29  1.18  1.05, 1.33  1.03  0.94, 1.14   3–6 families in building  258  19  14  12  1.24  1.11, 1.40  1.05  0.96, 1.15   >6 families in building  723  53  45  39  1.23  1.10, 1.38  1.04  0.65, 1.14  Neighborhood TB incidence                   Low  35  2  36  30  1.00  Referent  1.00  Referent   Medium  530  38  67  56  1.99  1.57, 2.52  1.73  1.35, 2.20   High  848  60  17  14  1.80  1.42, 2.28  1.62  1.26, 2.06  Neighborhood population density, no. of persons per square mile                   <20,000  135  10  55  46  1.00  Referent  1.00  Referent   20,000–34,999  537  38  41  34  1.31  1.19, 1.44  1.15  1.06, 1.26   35,000–49,999  255  18  14  12  1.33  1.21, 1.47  1.16  1.07, 1.26   ≥50,000  486  34  10  8  1.38  1.26, 1.51  1.18  1.08, 1.29  Neighborhood poverty levele                   Low  19  1  24  20  1.00  Referent  1.00  Referent   Medium  501  35  56  47  2.04  1.45, 2.85  1.56  1.08, 2.27   High  503  36  24  20  2.16  1.54, 3.02  1.57  1.08, 2.28   Very high  390  28  16  13  2.17  1.55, 3.04  1.54  1.06, 2.24  Characteristic  ≥1 Potential Source Case Identified (n = 1,413)  No Potential Source Case Identified (n = 120)  Unadjusted RR  Adjusted RR  No. of Children  %  No. of Children  %  RR  95% CI  RR  95% CI  Year reported to DOHMH                   2006  319  23  16  13  1.05  0.99, 1.12  —b     2007  257  18  13  11  1.03  0.98, 1.12  —     2008  255  18  17  14  0.98  0.97, 1.10  —     2009  191  14  23  19  0.97  0.91, 1.06  —     2010  147  10  20  17  0.96  0.89, 1.05  —     2011  135  10  20  17  1.00  0.88, 1.04  —     2012  109  8  11  9  1.00  Referent  —    Age at reporting, years                   <1  35  2  11  9  1.00  Referent  1.00  Referent   1  354  25  43  36  1.17  0.99, 1.38  1.13  0.98, 1.30   2  292  21  25  21  1.21  1.03, 1.43  1.16  1.01, 1.33   3  325  23  24  20  1.22  1.04, 1.44  1.18  1.03, 1.36   4  407  29  17  14  1.26  1.07, 1.49  1.19  1.04, 1.37  Birthplace                   US-bornc  692  49  58  48  1.00  Referent  —     Foreign-born  445  31  35  29  1.00  0.97, 1.04  —     Unknown  276  20  27  23  0.99  0.95, 1.03  —    Residence typed                   1-family dwelling  71  5  22  19  1.00  Referent  1.00  Referent   2-family dwelling  304  22  33  29  1.18  1.05, 1.33  1.03  0.94, 1.14   3–6 families in building  258  19  14  12  1.24  1.11, 1.40  1.05  0.96, 1.15   >6 families in building  723  53  45  39  1.23  1.10, 1.38  1.04  0.65, 1.14  Neighborhood TB incidence                   Low  35  2  36  30  1.00  Referent  1.00  Referent   Medium  530  38  67  56  1.99  1.57, 2.52  1.73  1.35, 2.20   High  848  60  17  14  1.80  1.42, 2.28  1.62  1.26, 2.06  Neighborhood population density, no. of persons per square mile                   <20,000  135  10  55  46  1.00  Referent  1.00  Referent   20,000–34,999  537  38  41  34  1.31  1.19, 1.44  1.15  1.06, 1.26   35,000–49,999  255  18  14  12  1.33  1.21, 1.47  1.16  1.07, 1.26   ≥50,000  486  34  10  8  1.38  1.26, 1.51  1.18  1.08, 1.29  Neighborhood poverty levele                   Low  19  1  24  20  1.00  Referent  1.00  Referent   Medium  501  35  56  47  2.04  1.45, 2.85  1.56  1.08, 2.27   High  503  36  24  20  2.16  1.54, 3.02  1.57  1.08, 2.28   Very high  390  28  16  13  2.17  1.55, 3.04  1.54  1.06, 2.24  Abbreviations: CI, confidence interval; DOHMH, Department of Health and Mental Hygiene; RR, relative risk; TB, tuberculosis. a RRs and 95% CIs were estimated using a modified Poisson regression model with a log-link and a robust sandwich variance estimator. b Dashes indicate characteristics that were not statistically associated with having a potential source case identified in the unadjusted analysis and therefore were not included in the adjusted modified Poisson regression model. c Includes children born in the United States and its territories. d Numbers may not sum to totals because of missing data. e Percentage of the population in a child’s United Hospital Fund neighborhood with a household income below the federal poverty threshold (low (<10% of residents below poverty limit), medium (10%–19.9%), high (20%–29.9%), or very high (≥30%)). View Large Table 2. Bivariate and Multivariate Associations Between Risk Factors for Exposure to Tuberculosis and Having at Least 1 Potential Source Case Identified Among Children Under Age 5 Years Reported to the New York City Department of Health and Mental Hygiene Bureau of Tuberculosis Control With Latent Tuberculosis Infection, New York, New York, 2006–2012a Characteristic  ≥1 Potential Source Case Identified (n = 1,413)  No Potential Source Case Identified (n = 120)  Unadjusted RR  Adjusted RR  No. of Children  %  No. of Children  %  RR  95% CI  RR  95% CI  Year reported to DOHMH                   2006  319  23  16  13  1.05  0.99, 1.12  —b     2007  257  18  13  11  1.03  0.98, 1.12  —     2008  255  18  17  14  0.98  0.97, 1.10  —     2009  191  14  23  19  0.97  0.91, 1.06  —     2010  147  10  20  17  0.96  0.89, 1.05  —     2011  135  10  20  17  1.00  0.88, 1.04  —     2012  109  8  11  9  1.00  Referent  —    Age at reporting, years                   <1  35  2  11  9  1.00  Referent  1.00  Referent   1  354  25  43  36  1.17  0.99, 1.38  1.13  0.98, 1.30   2  292  21  25  21  1.21  1.03, 1.43  1.16  1.01, 1.33   3  325  23  24  20  1.22  1.04, 1.44  1.18  1.03, 1.36   4  407  29  17  14  1.26  1.07, 1.49  1.19  1.04, 1.37  Birthplace                   US-bornc  692  49  58  48  1.00  Referent  —     Foreign-born  445  31  35  29  1.00  0.97, 1.04  —     Unknown  276  20  27  23  0.99  0.95, 1.03  —    Residence typed                   1-family dwelling  71  5  22  19  1.00  Referent  1.00  Referent   2-family dwelling  304  22  33  29  1.18  1.05, 1.33  1.03  0.94, 1.14   3–6 families in building  258  19  14  12  1.24  1.11, 1.40  1.05  0.96, 1.15   >6 families in building  723  53  45  39  1.23  1.10, 1.38  1.04  0.65, 1.14  Neighborhood TB incidence                   Low  35  2  36  30  1.00  Referent  1.00  Referent   Medium  530  38  67  56  1.99  1.57, 2.52  1.73  1.35, 2.20   High  848  60  17  14  1.80  1.42, 2.28  1.62  1.26, 2.06  Neighborhood population density, no. of persons per square mile                   <20,000  135  10  55  46  1.00  Referent  1.00  Referent   20,000–34,999  537  38  41  34  1.31  1.19, 1.44  1.15  1.06, 1.26   35,000–49,999  255  18  14  12  1.33  1.21, 1.47  1.16  1.07, 1.26   ≥50,000  486  34  10  8  1.38  1.26, 1.51  1.18  1.08, 1.29  Neighborhood poverty levele                   Low  19  1  24  20  1.00  Referent  1.00  Referent   Medium  501  35  56  47  2.04  1.45, 2.85  1.56  1.08, 2.27   High  503  36  24  20  2.16  1.54, 3.02  1.57  1.08, 2.28   Very high  390  28  16  13  2.17  1.55, 3.04  1.54  1.06, 2.24  Characteristic  ≥1 Potential Source Case Identified (n = 1,413)  No Potential Source Case Identified (n = 120)  Unadjusted RR  Adjusted RR  No. of Children  %  No. of Children  %  RR  95% CI  RR  95% CI  Year reported to DOHMH                   2006  319  23  16  13  1.05  0.99, 1.12  —b     2007  257  18  13  11  1.03  0.98, 1.12  —     2008  255  18  17  14  0.98  0.97, 1.10  —     2009  191  14  23  19  0.97  0.91, 1.06  —     2010  147  10  20  17  0.96  0.89, 1.05  —     2011  135  10  20  17  1.00  0.88, 1.04  —     2012  109  8  11  9  1.00  Referent  —    Age at reporting, years                   <1  35  2  11  9  1.00  Referent  1.00  Referent   1  354  25  43  36  1.17  0.99, 1.38  1.13  0.98, 1.30   2  292  21  25  21  1.21  1.03, 1.43  1.16  1.01, 1.33   3  325  23  24  20  1.22  1.04, 1.44  1.18  1.03, 1.36   4  407  29  17  14  1.26  1.07, 1.49  1.19  1.04, 1.37  Birthplace                   US-bornc  692  49  58  48  1.00  Referent  —     Foreign-born  445  31  35  29  1.00  0.97, 1.04  —     Unknown  276  20  27  23  0.99  0.95, 1.03  —    Residence typed                   1-family dwelling  71  5  22  19  1.00  Referent  1.00  Referent   2-family dwelling  304  22  33  29  1.18  1.05, 1.33  1.03  0.94, 1.14   3–6 families in building  258  19  14  12  1.24  1.11, 1.40  1.05  0.96, 1.15   >6 families in building  723  53  45  39  1.23  1.10, 1.38  1.04  0.65, 1.14  Neighborhood TB incidence                   Low  35  2  36  30  1.00  Referent  1.00  Referent   Medium  530  38  67  56  1.99  1.57, 2.52  1.73  1.35, 2.20   High  848  60  17  14  1.80  1.42, 2.28  1.62  1.26, 2.06  Neighborhood population density, no. of persons per square mile                   <20,000  135  10  55  46  1.00  Referent  1.00  Referent   20,000–34,999  537  38  41  34  1.31  1.19, 1.44  1.15  1.06, 1.26   35,000–49,999  255  18  14  12  1.33  1.21, 1.47  1.16  1.07, 1.26   ≥50,000  486  34  10  8  1.38  1.26, 1.51  1.18  1.08, 1.29  Neighborhood poverty levele                   Low  19  1  24  20  1.00  Referent  1.00  Referent   Medium  501  35  56  47  2.04  1.45, 2.85  1.56  1.08, 2.27   High  503  36  24  20  2.16  1.54, 3.02  1.57  1.08, 2.28   Very high  390  28  16  13  2.17  1.55, 3.04  1.54  1.06, 2.24  Abbreviations: CI, confidence interval; DOHMH, Department of Health and Mental Hygiene; RR, relative risk; TB, tuberculosis. a RRs and 95% CIs were estimated using a modified Poisson regression model with a log-link and a robust sandwich variance estimator. b Dashes indicate characteristics that were not statistically associated with having a potential source case identified in the unadjusted analysis and therefore were not included in the adjusted modified Poisson regression model. c Includes children born in the United States and its territories. d Numbers may not sum to totals because of missing data. e Percentage of the population in a child’s United Hospital Fund neighborhood with a household income below the federal poverty threshold (low (<10% of residents below poverty limit), medium (10%–19.9%), high (20%–29.9%), or very high (≥30%)). View Large Age at reporting, neighborhood TB incidence, neighborhood population density, and neighborhood poverty level remained significantly associated with identification of a potential source case in the adjusted model. Children who resided in neighborhoods with medium or high TB incidence (relative risk = 1.73 (95% confidence interval: 1.35, 2.20) and relative risk = 1.62 (95% confidence interval: 1.26, 2.06), respectively) or in neighborhoods with ≥10% of residents living below the federal poverty limit had the highest risk of having a potential source case identified when compared with those living in neighborhoods with a low TB incidence or low poverty, respectively (Table 2). DISCUSSION Analyzing reports of young children with LTBI by demographic characteristics and by distance from known infectious TB cases at the time of LTBI diagnosis revealed patterns about the burden of LTBI in NYC, as well as locations where TB transmission may have been missed using standard TB control practices. Among the 1,717 children reported to DOHMH with LTBI during 2006–2012, the majority (64%) were born in the United States. This finding differs from previous research among young children in low-TB-incidence countries where foreign birth has been consistently identified as a risk factor for LTBI (21–25). The deviation from this trend in our study, when combined with the young average age of the children (2.9 years), indicate that recent transmission of M. tuberculosis may still be happening in NYC despite decreases in TB rates for over 2 decades. Though information on foreign travel (21, 23–25) and parental country of birth (26) was not available for analysis in the present investigation, these factors may serve as important modifiers of this relationship and should be explored in future research. While the demographic characteristics of children with LTBI suggest that local TB transmission may have occurred, we also employed geospatial tools to find potential source cases for children. This process differs from a standard associate investigation in that it finds potential source cases who may have infected a young child with TB through close proximity regardless of known exposure, instead of searching for TB patients who infected a young child with TB through household or close contact (12). While it was not an active case-finding technique, this approach offered an efficient alternative for detecting patients who potentially transmitted TB to young children. The importance of exploring new methods to efficiently uncover ongoing TB transmission at the local level was underscored by the low yield (35%) of source-case and cluster investigations on the 72 children diagnosed with active TB disease during the study period. This is an important consideration for underresourced TB control programs. This geospatial method found a potential source case for almost all children with a valid address who were not known to have contact with a TB case (92%). Interestingly, the proportion of children with a potential source case identified decreased significantly across the study period. This pattern mirrors the steady declines observed in the number and rate of children reported to DOHMH with LTBI. The current analysis did not identify the drivers behind these reductions (e.g., changes in testing for LTBI, declines in knowledge of reporting requirements, or actual decreases in numbers of children with LTBI), and future investigations should examine these trends further. Among the potential source-case matches identified, assessment of risk factors enabled us to evaluate elements associated with potential TB transmission in NYC. For example, 27 children lived in the same residential building as a TB case; none of these children had documented contact with a TB patient, and most had been born in the United States (78%). Given that these children were in general a low-risk group for LTBI (24, 25), these matches provide strong evidence for local, recent TB transmission. However, this study was not equipped to characterize the mechanism of TB transmission to young children. Though it is considered rare, children may have been infected through casual contact with a TB patient in their residential building, an event which has been documented in previous investigations (27, 28). Alternatively, these children may have been in contact with a TB patient who did not name them during contact investigations. Both situations highlight limitations of core TB control methods, which depend on TB patients to recall and report contacts (13), and thereby the need for novel ways to detect transmission to high-risk groups. Monitoring reports of LTBI in young children to identify those living in the same building as a recent TB patient could be an important mechanism for uncovering sites where TB transmission may be happening and thus TB patients who may require a more in-depth contact investigation. On a broader scale, geographic and multivariate analysis provided insight into communities where transmission may be ongoing. Children living in neighborhoods with a high TB incidence, ≥50,000 persons per square mile, or more than 10% of the population living below the federal poverty limit were more likely to have a potential source case identified. On an individual level, children who lived in buildings with more than 1 family also had greater risk of source-case identification in the bivariate analysis. These results align with knowledge of TB transmission dynamics, in which crowding, urban dwelling, and residence in high-incidence areas are consistently recognized as social determinants of exposure to M. tuberculosis (29). Therefore, as expected, potential transmission of TB in NYC was associated with living in high-risk neighborhoods and buildings. This finding helps inform DOHMH control and prevention efforts. While resources may not allow for case management of every child under age 5 with LTBI reported in NYC, knowledge of local epidemiology and use of spatial analysis tools can help to prioritize children with a potential source case in NYC. For example, TB surveillance data could be used to identify young children reported with LTBI who live in the same residential building as a recent TB patient. These matches may signal the need for the TB control program to conduct a more through contact investigation of the patient with active TB disease. These efforts may help to yield additional missed contacts eligible for testing and treatment for LTBI or TB disease. These monitoring methods can also help identify regions or pockets with potential TB transmission and consequently areas that may require outreach to prevent future TB cases, especially among this young and high-risk population. This study was not without limitations. Underreporting of LTBI in young children by NYC health-care providers probably occurred, and it is difficult to predict how this bias may have affected the results. Children may also have been infected with TB prior to the identification and treatment of their potential source-case match, and consequently some matches may not have represented recent local transmission. Furthermore, the data for this investigation were collected in the course of routine TB control activities and therefore were not gathered for research purposes. Given that children reported to have a positive test for TB infection do not receive case management from DOHMH staff, demographic and clinical data (including chest radiograph results) were missing for some children. As a result, complete information about risk factors, such as parents’ country of birth (26), foreign travel (21, 23–25), and time spent in congregate settings such as day-care centers or hospitals, was not available for analysis. While knowledge of these variables would enrich the understanding of risk factors, comprehensive information on children’s neighborhoods and residential buildings still provided a unique and detailed view on regions where transmission may occur. Finally, there has been a lack of data investigating the sensitivity and specificity of interferon-γ release assay tests in children under 5 years of age, and Centers for Disease Control and Prevention guidance recommends tuberculin skin tests as the preferred test for this age group (30). The children described in this investigation were tested with both tuberculin skin tests and interferon-γ release assays, and we are unable to project how this influenced the results, although the vast majority (98%) were tested using tuberculin skin tests. Additionally, false-positive test results are possible, since children with LTBI who were born in the United States had unknown risk factors for targeted TB infection testing and children with LTBI who were born outside of the United States may have received Bacillus Calmette-Guérin immunization (12). In conclusion, this evaluation provided important insights into the burden of LTBI among young children in NYC and demonstrated innovative use of LTBI surveillance data in pursuit of the goal of TB elimination. A number of findings from this investigation, such as the high proportion of children with LTBI born in the United States and the 27 children who lived in the same building as an infectious TB case, indicate that undetected TB transmission may be occurring in NYC. Potential TB transmission, defined as a match between a potential source case and a child with LTBI, was associated with residence in neighborhoods and buildings with high population density, poverty, and TB incidence. Examination of reports of LTBI in young children could be used as a method for DOHMH to locate buildings or regions where TB transmission may have occurred and subsequently TB patients who might require additional contact investigation or areas for targeting outreach to providers about testing, treating, and reporting LTBI among young children. These efforts would help to prevent TB disease in this sentinel population. ACKNOWLEDGMENTS Author affiliations: Centers for Disease Control and Prevention/Council of State and Territorial Epidemiologists Applied Epidemiology Fellowship Program, Atlanta, Georgia (Jennifer Sanderson Slutsker); and New York City Department of Health and Mental Hygiene, Long Island City, New York (Jennifer Sanderson Slutsker, Lisa Trieu, Aldo Crossa, Shama Desai Ahuja). J.S.S. was supported by an appointment to the Applied Epidemiology Fellowship Program, which is administered by the Council of State and Territorial Epidemiologists and funded by the Centers for Disease Control and Prevention (cooperative agreement 1U380T000143-01). We acknowledge field and surveillance staff from the Bureau of Tuberculosis Control, New York City Department of Health and Mental Hygiene, for their contribution to data collection. This project has been presented in oral or poster sessions at the International Conference on Emerging Infectious Diseases, Atlanta, Georgia (August 24–26, 2015); the Council of State and Territorial Epidemiologists Annual Conference, Boston, Massachusetts (June 14–18, 2015); the National Tuberculosis Conference, Atlanta, Georgia (June 8–11, 2015); and the New York City Epidemiology Forum, New York, New York (February 27, 2015). Conflict of interest: none declared. Abbreviations DOHMH Department of Health and Mental Hygiene LTBI latent tuberculosis infection NYC New York City TB tuberculosis UHF United Hospital Fund REFERENCES 1 World Health Organization. The End TB Strategy. Geneva, Switzerland: World Health Organization; 2015. http://www.who.int/tb/End_TB_brochure.pdf. Accessed January 28, 2017. 2 Centers for Disease Control and Prevention. Latent Tuberculosis Infection: A Guide for Primary Health Care Providers. Atlanta, GA: Centers for Disease Control and Prevention; 2013. https://www.cdc.gov/tb/publications/ltbi/default.htm. Accessed May 18, 2017. 3 Shingadia D, Novelli V. Diagnosis and treatment of tuberculosis in children. Lancet Infect Dis . 2003; 3( 10): 624– 632. Google Scholar CrossRef Search ADS PubMed  4 New York City Department of Health and Mental Hygiene. Article 11: Reportable Diseases and Conditions. (New York City Health Code). https://www1.nyc.gov/assets/doh/downloads/pdf/about/healthcode/health-code-article11.pdf. Accessed October 25, 2017. 5 Fujiwara P. Discontinuation of Source Case Investigations for TST Positive Children Less Than Three Years Old. (Memorandum). New York, NY: New York City Department of Health and Mental Hygiene; 2000. 6 Driver CR, Cordova IM, Munsiff SS. Targeting tuberculosis testing: the yield of source case investigations for young children with reactive tuberculin skin tests. Public Health Rep . 2002; 117( 4): 366– 372. Google Scholar CrossRef Search ADS PubMed  7 Moonan PK, Marruffo M, Manguia-Bayona G, et al.  . Tuberculosis: what is the yield of associate investigations in non-BCG-immunized children with positive tuberculin skin tests? Int J Tuberc Lung Dis . 2005; 9( 3): 322– 327. Google Scholar PubMed  8 Sullam PM, Slutkin G, Hopewell PC. The benefits of evaluating close associates of child tuberculin reactors from a high prevalence group. Am J Public Health . 1986; 76( 9): 1109– 1111. 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Clinical Policies and Protocols: Bureau of Tuberculosis Control. Long Island City, NY: New York City Department of Health and Mental Hygiene; 2008. https://www1.nyc.gov/assets/doh/downloads/pdf/tb/tb-protocol.pdf. Accessed January 28, 2017. 14 Comstock GW, Livesay VT, Woolpert SF. The prognosis of a positive tuberculin reaction in childhood and adolescence. Am J Epidemiol . 1974; 99( 2): 131– 138. Google Scholar CrossRef Search ADS PubMed  15 Centers for Disease Control and Prevention. National Notifiable Diseases Surveillance System (NNDSS). Tuberculosis (TB) (Mycobacterium tuberculosis). 2009 case definition. https://wwwn.cdc.gov/nndss/conditions/tuberculosis/case-definition/2009/. Published 2009. Accessed May 18, 2017. 16 Perri BR, Proops D, Moonan PK, et al.  . Mycobacterium tuberculosis cluster with developing drug resistance, New York, New York, USA, 2003–2009. Emerg Infect Dis . 2011; 17( 3): 372– 378. Google Scholar CrossRef Search ADS PubMed  17 United Hospital Fund. 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Updated guidelines for using interferon gamma release assays to detect Mycobacterium tuberculosis infection—United States, 2010. MMWR Recomm Rep . 2010; 59( RR-5): 1– 25. Google Scholar PubMed  © The Author(s) 2018. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com. This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/about_us/legal/notices) http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png American Journal of Epidemiology Oxford University Press

Using Reports of Latent Tuberculosis Infection Among Young Children to Identify Tuberculosis Transmission in New York City, 2006–2012

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Oxford University Press
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© The Author(s) 2018. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
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10.1093/aje/kwx354
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Abstract

Abstract The presence of latent tuberculosis infection (LTBI) in young children indicates recent tuberculosis (TB) transmission. We reviewed surveillance reports of children with LTBI to assess whether more follow-up is needed to prevent TB in this high-risk population. Data on all children under 5 years of age who were reported by health-care providers or laboratories to the New York City Department of Health during 2006–2012 were abstracted from the TB surveillance and case management system, and those with LTBI were identified. Potential source cases, defined as any infectious TB case diagnosed in the 2 years before a child was reported and whose residence was within 0.5 miles (0.8 km) of the child’s residence, were identified. Neighborhood risk factors for TB transmission were examined. Among 3,511 reports of children under age 5 years, 1,722 (49%) had LTBI. The children were aged 2.9 years, on average, and most (64%) had been born in the United States. A potential source case was identified for 92% of the children; 27 children lived in the same building as a TB patient. Children with potential source cases were more likely to reside in neighborhoods with high TB incidence, poverty, and population density. The high proportion of children born in the United States and the young average age of the cases imply that undetected TB transmission occurred. Monitoring reports could be used to identify places where transmission occurred, and additional investigation is needed to prevent TB disease. children, disease transmission, geographic analysis, latent tuberculosis infection, tuberculosis Identification and treatment of young children with latent tuberculosis infection (LTBI) is a priority for tuberculosis (TB) control programs and an emphasis of the recently published World Health Organization End TB Strategy (1). LTBI in young children is indicative of recent transmission of Mycobacterium tuberculosis (2). Furthermore, young children are at greater risk for rapidly progressing to active TB disease as well as developing severe forms of disease (3). Consequently, the New York City (NYC) Health Code mandates the reporting of any positive TB test result in a child under 5 years of age, in addition to children who have or are suspected to have TB disease and children identified as contacts of an infectious TB patient (4). LTBI in children under 5 years of age is reportable because these infections are considered sentinel events indicating recent transmission (2). In NYC, all children with suspected or confirmed TB disease and children who have had contact with an infectious individual are closely case-managed by the health department to ensure appropriate evaluation and adherence to treatment (e.g., patient interviews, monthly review of patient progress). However, children reported to have a positive test for TB infection are not consistently monitored. This policy of not investigating reported cases of LTBI in children under 5 years of age was established in NYC in 2000 (5). Previously, associate investigations were conducted for all children aged ≤3 years reported with LTBI to identify the infectious TB patient who was the source of infection for each child (5). The rationale behind these investigations was that young children had limited sources of exposure and were recently infected with TB (5). However, these investigations were found to require extensive resources and often yielded minimal information on source cases (6–8). For example, in NYC from January 1, 1996, through June 30, 1998, only 2 source cases were identified among the 207 children aged ≤3 years with LTBI who had an associate investigation performed (6). Consequently, active monitoring of children with LTBI ceased in NYC (5). Since that time, the rate of active TB disease has decreased nationally in the United States (9) and locally in NYC (10). Accordingly, the focus for US TB programs has started to shift from maintaining control of TB disease to finding and treating persons with LTBI toward the goal of TB elimination (11). Furthermore, global interest in LTBI has been renewed by the publication of the World Health Organization’s End TB Strategy (1), which aims to increase the number of children started on preventive treatment for LTBI. This emerging attention to LTBI offers a critical opportunity to reassess the burden and management of LTBI among high-priority populations for TB prevention and elimination, especially young children. In this investigation, we characterized young children reported with LTBI in NYC and explored novel strategies for identifying potential source cases for these children. We employed geographic analysis to find infectious TB patients who were in close physical and temporal proximity to young children with LTBI and then evaluated the risk factors for having a potential source case identified. While it is not a means to detect new TB patients as in a traditional associate or source-case investigation (12), we aimed to use readily available surveillance data to explore whether this method could uncover locations with potential TB transmission. METHODS Study population All persons reported to the NYC Department of Health and Mental Hygiene (DOHMH) Bureau of Tuberculosis Control during 2006–2012 who were under 5 years of age at the time of report were abstracted from the Bureau of Tuberculosis Control’s electronic surveillance and case management registry (Consilience Software, Inc., Austin, Texas). Among these children, we identified those with LTBI, defined as having 1) a positive result from a tuberculin skin test or a Food and Drug Administration-approved blood-based test for TB infection and 2) no signs or symptoms of TB disease, such as documentation of cough or an abnormal chest radiograph. The annual number of LTBI cases and the rate of reported LBTI per 100,000 population in children under age 5 years were calculated. All population estimates used in rate calculations were based on DOHMH population estimates that were modified from US Census Bureau intercensal estimates. Identification of potential source cases Each child with LTBI was matched to TB patients who were considered potential sources of infection (definition below). Children who were living in a health-care facility at the time of report or who had known contact with a TB patient were excluded. Children with documented interaction with a TB patient were removed under the assumption that this TB patient would have been the child’s source of LTBI. Potential source cases included patients with active TB disease in NYC who were verified by DOHMH as a TB case during 2004–2013. To capture patients most likely to be infectious, cases were limited to those aged ≥5 years who had a positive culture for M. tuberculosis complex from a respiratory specimen. Cases were also limited to those with a known address living in the community; those with only a correctional or health-care facility address were excluded. A TB patient was defined as a potential source case to a child with LTBI if 1) the patient resided less than 0.5 miles (0.8 km) from the child’s residence and 2) the child was reported to the DOHMH either during the 3-month period prior to the patient’s diagnosis (infectious period) (13) or up to 2 years after the patient’s TB diagnosis (recent transmission of M. tuberculosis (14)). The diagnosis date was defined as the date on which the patient was verified to have active TB disease, per the Centers for Disease Control and Prevention’s case definition (15). A distance of less than 0.5 miles (0.8 km) was selected on the basis of the DOHMH’s programmatic definition of a possible epidemiologic link between individuals (16). We geocoded the address of residence for both children with LTBI and potential source cases, and then matched them by geodesic distance using ArcGIS software, version 10 (Environmental Systems Research Institute, Redlands, California). Characteristics associated with potential source case identification Neighborhood characteristics Children’s neighborhoods of residence (as defined by the NYC United Hospital Fund (UHF) (17)) were categorized according to the TB incidence rate, population density (number of persons per square mile (per 1.6 km2)), and poverty level at the time of report. Based on the year of report to the DOHMH and the annual TB incidence rate within their neighborhoods, children were categorized as residing in neighborhoods with high TB incidence (neighborhood rate (10) > citywide rate (10)), medium TB incidence (citywide rate (10) ≥ neighborhood rate (10) ≥ national rate (9)), or low TB incidence (neighborhood rate (10) < national rate (9)). The population density of each child’s UHF area was calculated by dividing the annual population estimates by the UHF area (in squared miles). Neighborhood-level poverty was characterized for children as the percentage of the population in their UHF neighborhood with a household income below the poverty threshold set by the federal government. In alignment with DOHMH area-based poverty guidelines (18), 5-year American Community Survey poverty data from 2007– 2011 were used to divide UHF neighborhoods into 4 categories indicating the percentage of residents living below the federal poverty limit: low (<10%), medium (10%–19.9%), high (20%–29.9%), and very high (≥30%). Residence characteristics We also described the types of buildings where children lived, since residing in a crowded setting serves as a risk factor for exposure to TB. Every property in NYC is classified using Real Property Assessment Division codes, and we identified the code for each child’s residential building (19). Based on Real Property Assessment Division codes, children’s residence types were divided into 4 mutually exclusive groups: 1) single-family dwelling, 2) 2-family dwelling, 3) building with 6 families or less (e.g., walk-up apartment buildings), and 4) building with more than 6 families (e.g., elevator apartment buildings). These categories were defined on the basis of Real Property Assessment Division categories, which separate NYC building sizes based on the cutpoint of 6 families. Children whose codes indicated a nonresidential building were excluded from further analysis. Statistical analysis Descriptive statistics were generated to characterize the age, sex, and birthplace of the study population. We used the Cochran-Armitage trend test to investigate whether the proportion of children with a potential source case identified differed from 2006 to 2012. To identify factors associated with identification of a possible source case, we compared the year of report to the DOHMH, age at report, birthplace, residence type, neighborhood TB incidence, neighborhood population density, and neighborhood poverty level of children with at least 1 potential source-case match with those characteristics in children who had no source case identified using a modified Poisson regression model with a log-link and robust sandwich variance estimator (20). Characteristics significantly associated with having a potential source case identified were included in an adjusted modified Poisson regression model, and relative risks and 95% confidence intervals were calculated. All analyses were conducted in SAS, version 9.2 (SAS Institute, Inc., Cary, North Carolina). Data presented were obtained as part of routine TB surveillance and case management activities. Analyses were conducted for program evaluation purposes and therefore were not subject to review by the DOHMH Institutional Review Board. RESULTS Among 3,511 children under 5 years of age reported to the DOHMH during 2006–2012, 1,722 (49%) were identified as having LTBI and 1,533 (44%) were eligible for potential source case identification after excluding those who had had known contact with a TB case and those without a valid address of residence in the community (Figure 1). The number and rate of children reported with LTBI decreased steadily from 377 children in 2006 (72.5 reports per 100,000 population aged <5 years) to 128 children in 2012 (23.5 reports per 100,000 population aged <5 years). Children with LTBI had a mean age of 2.9 years at the time of first report (median age at time of first report, 3.0 years), and about half were female (53%) (Table 1). Among the 1,399 (81%) children for whom the country of birth was recorded, the majority were US-born (64%). Among the 3,511 reports of children under age 5 years from 2006–2012, there were 72 confirmed cases of TB disease in children under age 5 years. The majority of children with confirmed TB disease did not have a known link to a source case through source-case or cluster investigations (n = 47; 65%). Figure 1. View largeDownload slide Identification of children with latent tuberculosis (TB) infection among all persons under age 5 years reported to the New York City (NYC) Department of Health and Mental Hygiene Bureau of Tuberculosis Control, New York, New York, 2006–2012. Figure 1. View largeDownload slide Identification of children with latent tuberculosis (TB) infection among all persons under age 5 years reported to the New York City (NYC) Department of Health and Mental Hygiene Bureau of Tuberculosis Control, New York, New York, 2006–2012. Table 1. Demographic Characteristics of All Children Under Age 5 Years Reported to the New York City Department of Health and Mental Hygiene Bureau of Tuberculosis Control With Latent Tuberculosis Infection (n = 1,717), New York, New York, 2006–2012a Characteristic  No. of Children  %  Age at first report, yearsb  2.9 (1.3)  Sexc       Female  903  53   Male  813  47  Birthplacec       US-bornd  890  64   Foreign-born  509  36  Country of birthe       Bangladesh  68  13   China  44  9   Dominican Republic  66  13   Jamaica  19  4   Mexico  55  11   Nigeria  28  6   Pakistan  34  7   Other  195  38  Characteristic  No. of Children  %  Age at first report, yearsb  2.9 (1.3)  Sexc       Female  903  53   Male  813  47  Birthplacec       US-bornd  890  64   Foreign-born  509  36  Country of birthe       Bangladesh  68  13   China  44  9   Dominican Republic  66  13   Jamaica  19  4   Mexico  55  11   Nigeria  28  6   Pakistan  34  7   Other  195  38  a There were 5 children reported more than once with latent tuberculosis infection between 2006 and 2012. This table includes the first reported case for children reported more than 1 time between 2006 and 2012 (n = 1,717). b Values are expressed as mean (standard deviation). c Numbers may not sum to 1,717 because of missing data. d Includes children born in the United States and its territories. e Proportion calculated among children born outside of the United States (n = 509). Table 1. Demographic Characteristics of All Children Under Age 5 Years Reported to the New York City Department of Health and Mental Hygiene Bureau of Tuberculosis Control With Latent Tuberculosis Infection (n = 1,717), New York, New York, 2006–2012a Characteristic  No. of Children  %  Age at first report, yearsb  2.9 (1.3)  Sexc       Female  903  53   Male  813  47  Birthplacec       US-bornd  890  64   Foreign-born  509  36  Country of birthe       Bangladesh  68  13   China  44  9   Dominican Republic  66  13   Jamaica  19  4   Mexico  55  11   Nigeria  28  6   Pakistan  34  7   Other  195  38  Characteristic  No. of Children  %  Age at first report, yearsb  2.9 (1.3)  Sexc       Female  903  53   Male  813  47  Birthplacec       US-bornd  890  64   Foreign-born  509  36  Country of birthe       Bangladesh  68  13   China  44  9   Dominican Republic  66  13   Jamaica  19  4   Mexico  55  11   Nigeria  28  6   Pakistan  34  7   Other  195  38  a There were 5 children reported more than once with latent tuberculosis infection between 2006 and 2012. This table includes the first reported case for children reported more than 1 time between 2006 and 2012 (n = 1,717). b Values are expressed as mean (standard deviation). c Numbers may not sum to 1,717 because of missing data. d Includes children born in the United States and its territories. e Proportion calculated among children born outside of the United States (n = 509). Identification of potential source cases The 1,533 children who were eligible for potential source case identification were matched with 4,958 TB patients who met the eligibility criteria for analysis. Overall, 1,413 children with LTBI (92% of the 1,533 eligible children) matched to 3,045 patients with active TB disease (61% of the 4,958 eligible TB patients). The median number of matches per child with a match was 6 TB patients (interquartile range, 3–15), and a total of 14,066 matches were identified. There were 404 children who matched with 1–3 TB patients. The majority of these children lived in medium- or low-TB-incidence neighborhoods (277 children; 69%) and neighborhoods with fewer than 35,000 persons per square mile (256 children; 63%). On the other end of the spectrum, there were 318 children with more than 15 matches. The majority of these children lived in high-TB-incidence neighborhoods (285 children; 90%) and neighborhoods with 35,000 or more persons per square mile (183 children; 58%). We identified 29 matches between TB patients and children who lived in the same residential building. Among these 29 matches, there were 29 unique TB patients and 27 unique children with LTBI (i.e., 2 children matched with 2 different TB patients who lived in the same residential building). Of the 29 TB patients, 20 were acid-fast bacilli respiratory-smear positive (69%), and 8 showed cavities on a chest radiograph (28%). Of the 27 children, 21 had been born in the United States (78%) and 13 were ≤2 years of age at the time of report (48%). No TB patient and child with LTBI shared a last name or were known to be related. Characteristics associated with potential source-case identification The proportion of children with 1 or more potential source cases identified across the study period decreased from 95% in 2006 to 87% in 2011 (P < 0.01; Figure 2). In unadjusted analyses, almost all risk factors for exposure to or recent transmission of M. tuberculosis, including age at report, residence type, neighborhood TB incidence, neighborhood population density, and neighborhood poverty level, were associated with having a potential source case identified (Table 2). The only exceptions were birthplace and year of report. Figure 2. View largeDownload slide Number of children under age 5 years reported to the New York City Department of Health and Mental Hygiene Bureau of Tuberculosis Control with latent tuberculosis infection who had a potential source case identified by geospatial matching, New York, New York, 2006–2012. Figure 2. View largeDownload slide Number of children under age 5 years reported to the New York City Department of Health and Mental Hygiene Bureau of Tuberculosis Control with latent tuberculosis infection who had a potential source case identified by geospatial matching, New York, New York, 2006–2012. Table 2. Bivariate and Multivariate Associations Between Risk Factors for Exposure to Tuberculosis and Having at Least 1 Potential Source Case Identified Among Children Under Age 5 Years Reported to the New York City Department of Health and Mental Hygiene Bureau of Tuberculosis Control With Latent Tuberculosis Infection, New York, New York, 2006–2012a Characteristic  ≥1 Potential Source Case Identified (n = 1,413)  No Potential Source Case Identified (n = 120)  Unadjusted RR  Adjusted RR  No. of Children  %  No. of Children  %  RR  95% CI  RR  95% CI  Year reported to DOHMH                   2006  319  23  16  13  1.05  0.99, 1.12  —b     2007  257  18  13  11  1.03  0.98, 1.12  —     2008  255  18  17  14  0.98  0.97, 1.10  —     2009  191  14  23  19  0.97  0.91, 1.06  —     2010  147  10  20  17  0.96  0.89, 1.05  —     2011  135  10  20  17  1.00  0.88, 1.04  —     2012  109  8  11  9  1.00  Referent  —    Age at reporting, years                   <1  35  2  11  9  1.00  Referent  1.00  Referent   1  354  25  43  36  1.17  0.99, 1.38  1.13  0.98, 1.30   2  292  21  25  21  1.21  1.03, 1.43  1.16  1.01, 1.33   3  325  23  24  20  1.22  1.04, 1.44  1.18  1.03, 1.36   4  407  29  17  14  1.26  1.07, 1.49  1.19  1.04, 1.37  Birthplace                   US-bornc  692  49  58  48  1.00  Referent  —     Foreign-born  445  31  35  29  1.00  0.97, 1.04  —     Unknown  276  20  27  23  0.99  0.95, 1.03  —    Residence typed                   1-family dwelling  71  5  22  19  1.00  Referent  1.00  Referent   2-family dwelling  304  22  33  29  1.18  1.05, 1.33  1.03  0.94, 1.14   3–6 families in building  258  19  14  12  1.24  1.11, 1.40  1.05  0.96, 1.15   >6 families in building  723  53  45  39  1.23  1.10, 1.38  1.04  0.65, 1.14  Neighborhood TB incidence                   Low  35  2  36  30  1.00  Referent  1.00  Referent   Medium  530  38  67  56  1.99  1.57, 2.52  1.73  1.35, 2.20   High  848  60  17  14  1.80  1.42, 2.28  1.62  1.26, 2.06  Neighborhood population density, no. of persons per square mile                   <20,000  135  10  55  46  1.00  Referent  1.00  Referent   20,000–34,999  537  38  41  34  1.31  1.19, 1.44  1.15  1.06, 1.26   35,000–49,999  255  18  14  12  1.33  1.21, 1.47  1.16  1.07, 1.26   ≥50,000  486  34  10  8  1.38  1.26, 1.51  1.18  1.08, 1.29  Neighborhood poverty levele                   Low  19  1  24  20  1.00  Referent  1.00  Referent   Medium  501  35  56  47  2.04  1.45, 2.85  1.56  1.08, 2.27   High  503  36  24  20  2.16  1.54, 3.02  1.57  1.08, 2.28   Very high  390  28  16  13  2.17  1.55, 3.04  1.54  1.06, 2.24  Characteristic  ≥1 Potential Source Case Identified (n = 1,413)  No Potential Source Case Identified (n = 120)  Unadjusted RR  Adjusted RR  No. of Children  %  No. of Children  %  RR  95% CI  RR  95% CI  Year reported to DOHMH                   2006  319  23  16  13  1.05  0.99, 1.12  —b     2007  257  18  13  11  1.03  0.98, 1.12  —     2008  255  18  17  14  0.98  0.97, 1.10  —     2009  191  14  23  19  0.97  0.91, 1.06  —     2010  147  10  20  17  0.96  0.89, 1.05  —     2011  135  10  20  17  1.00  0.88, 1.04  —     2012  109  8  11  9  1.00  Referent  —    Age at reporting, years                   <1  35  2  11  9  1.00  Referent  1.00  Referent   1  354  25  43  36  1.17  0.99, 1.38  1.13  0.98, 1.30   2  292  21  25  21  1.21  1.03, 1.43  1.16  1.01, 1.33   3  325  23  24  20  1.22  1.04, 1.44  1.18  1.03, 1.36   4  407  29  17  14  1.26  1.07, 1.49  1.19  1.04, 1.37  Birthplace                   US-bornc  692  49  58  48  1.00  Referent  —     Foreign-born  445  31  35  29  1.00  0.97, 1.04  —     Unknown  276  20  27  23  0.99  0.95, 1.03  —    Residence typed                   1-family dwelling  71  5  22  19  1.00  Referent  1.00  Referent   2-family dwelling  304  22  33  29  1.18  1.05, 1.33  1.03  0.94, 1.14   3–6 families in building  258  19  14  12  1.24  1.11, 1.40  1.05  0.96, 1.15   >6 families in building  723  53  45  39  1.23  1.10, 1.38  1.04  0.65, 1.14  Neighborhood TB incidence                   Low  35  2  36  30  1.00  Referent  1.00  Referent   Medium  530  38  67  56  1.99  1.57, 2.52  1.73  1.35, 2.20   High  848  60  17  14  1.80  1.42, 2.28  1.62  1.26, 2.06  Neighborhood population density, no. of persons per square mile                   <20,000  135  10  55  46  1.00  Referent  1.00  Referent   20,000–34,999  537  38  41  34  1.31  1.19, 1.44  1.15  1.06, 1.26   35,000–49,999  255  18  14  12  1.33  1.21, 1.47  1.16  1.07, 1.26   ≥50,000  486  34  10  8  1.38  1.26, 1.51  1.18  1.08, 1.29  Neighborhood poverty levele                   Low  19  1  24  20  1.00  Referent  1.00  Referent   Medium  501  35  56  47  2.04  1.45, 2.85  1.56  1.08, 2.27   High  503  36  24  20  2.16  1.54, 3.02  1.57  1.08, 2.28   Very high  390  28  16  13  2.17  1.55, 3.04  1.54  1.06, 2.24  Abbreviations: CI, confidence interval; DOHMH, Department of Health and Mental Hygiene; RR, relative risk; TB, tuberculosis. a RRs and 95% CIs were estimated using a modified Poisson regression model with a log-link and a robust sandwich variance estimator. b Dashes indicate characteristics that were not statistically associated with having a potential source case identified in the unadjusted analysis and therefore were not included in the adjusted modified Poisson regression model. c Includes children born in the United States and its territories. d Numbers may not sum to totals because of missing data. e Percentage of the population in a child’s United Hospital Fund neighborhood with a household income below the federal poverty threshold (low (<10% of residents below poverty limit), medium (10%–19.9%), high (20%–29.9%), or very high (≥30%)). View Large Table 2. Bivariate and Multivariate Associations Between Risk Factors for Exposure to Tuberculosis and Having at Least 1 Potential Source Case Identified Among Children Under Age 5 Years Reported to the New York City Department of Health and Mental Hygiene Bureau of Tuberculosis Control With Latent Tuberculosis Infection, New York, New York, 2006–2012a Characteristic  ≥1 Potential Source Case Identified (n = 1,413)  No Potential Source Case Identified (n = 120)  Unadjusted RR  Adjusted RR  No. of Children  %  No. of Children  %  RR  95% CI  RR  95% CI  Year reported to DOHMH                   2006  319  23  16  13  1.05  0.99, 1.12  —b     2007  257  18  13  11  1.03  0.98, 1.12  —     2008  255  18  17  14  0.98  0.97, 1.10  —     2009  191  14  23  19  0.97  0.91, 1.06  —     2010  147  10  20  17  0.96  0.89, 1.05  —     2011  135  10  20  17  1.00  0.88, 1.04  —     2012  109  8  11  9  1.00  Referent  —    Age at reporting, years                   <1  35  2  11  9  1.00  Referent  1.00  Referent   1  354  25  43  36  1.17  0.99, 1.38  1.13  0.98, 1.30   2  292  21  25  21  1.21  1.03, 1.43  1.16  1.01, 1.33   3  325  23  24  20  1.22  1.04, 1.44  1.18  1.03, 1.36   4  407  29  17  14  1.26  1.07, 1.49  1.19  1.04, 1.37  Birthplace                   US-bornc  692  49  58  48  1.00  Referent  —     Foreign-born  445  31  35  29  1.00  0.97, 1.04  —     Unknown  276  20  27  23  0.99  0.95, 1.03  —    Residence typed                   1-family dwelling  71  5  22  19  1.00  Referent  1.00  Referent   2-family dwelling  304  22  33  29  1.18  1.05, 1.33  1.03  0.94, 1.14   3–6 families in building  258  19  14  12  1.24  1.11, 1.40  1.05  0.96, 1.15   >6 families in building  723  53  45  39  1.23  1.10, 1.38  1.04  0.65, 1.14  Neighborhood TB incidence                   Low  35  2  36  30  1.00  Referent  1.00  Referent   Medium  530  38  67  56  1.99  1.57, 2.52  1.73  1.35, 2.20   High  848  60  17  14  1.80  1.42, 2.28  1.62  1.26, 2.06  Neighborhood population density, no. of persons per square mile                   <20,000  135  10  55  46  1.00  Referent  1.00  Referent   20,000–34,999  537  38  41  34  1.31  1.19, 1.44  1.15  1.06, 1.26   35,000–49,999  255  18  14  12  1.33  1.21, 1.47  1.16  1.07, 1.26   ≥50,000  486  34  10  8  1.38  1.26, 1.51  1.18  1.08, 1.29  Neighborhood poverty levele                   Low  19  1  24  20  1.00  Referent  1.00  Referent   Medium  501  35  56  47  2.04  1.45, 2.85  1.56  1.08, 2.27   High  503  36  24  20  2.16  1.54, 3.02  1.57  1.08, 2.28   Very high  390  28  16  13  2.17  1.55, 3.04  1.54  1.06, 2.24  Characteristic  ≥1 Potential Source Case Identified (n = 1,413)  No Potential Source Case Identified (n = 120)  Unadjusted RR  Adjusted RR  No. of Children  %  No. of Children  %  RR  95% CI  RR  95% CI  Year reported to DOHMH                   2006  319  23  16  13  1.05  0.99, 1.12  —b     2007  257  18  13  11  1.03  0.98, 1.12  —     2008  255  18  17  14  0.98  0.97, 1.10  —     2009  191  14  23  19  0.97  0.91, 1.06  —     2010  147  10  20  17  0.96  0.89, 1.05  —     2011  135  10  20  17  1.00  0.88, 1.04  —     2012  109  8  11  9  1.00  Referent  —    Age at reporting, years                   <1  35  2  11  9  1.00  Referent  1.00  Referent   1  354  25  43  36  1.17  0.99, 1.38  1.13  0.98, 1.30   2  292  21  25  21  1.21  1.03, 1.43  1.16  1.01, 1.33   3  325  23  24  20  1.22  1.04, 1.44  1.18  1.03, 1.36   4  407  29  17  14  1.26  1.07, 1.49  1.19  1.04, 1.37  Birthplace                   US-bornc  692  49  58  48  1.00  Referent  —     Foreign-born  445  31  35  29  1.00  0.97, 1.04  —     Unknown  276  20  27  23  0.99  0.95, 1.03  —    Residence typed                   1-family dwelling  71  5  22  19  1.00  Referent  1.00  Referent   2-family dwelling  304  22  33  29  1.18  1.05, 1.33  1.03  0.94, 1.14   3–6 families in building  258  19  14  12  1.24  1.11, 1.40  1.05  0.96, 1.15   >6 families in building  723  53  45  39  1.23  1.10, 1.38  1.04  0.65, 1.14  Neighborhood TB incidence                   Low  35  2  36  30  1.00  Referent  1.00  Referent   Medium  530  38  67  56  1.99  1.57, 2.52  1.73  1.35, 2.20   High  848  60  17  14  1.80  1.42, 2.28  1.62  1.26, 2.06  Neighborhood population density, no. of persons per square mile                   <20,000  135  10  55  46  1.00  Referent  1.00  Referent   20,000–34,999  537  38  41  34  1.31  1.19, 1.44  1.15  1.06, 1.26   35,000–49,999  255  18  14  12  1.33  1.21, 1.47  1.16  1.07, 1.26   ≥50,000  486  34  10  8  1.38  1.26, 1.51  1.18  1.08, 1.29  Neighborhood poverty levele                   Low  19  1  24  20  1.00  Referent  1.00  Referent   Medium  501  35  56  47  2.04  1.45, 2.85  1.56  1.08, 2.27   High  503  36  24  20  2.16  1.54, 3.02  1.57  1.08, 2.28   Very high  390  28  16  13  2.17  1.55, 3.04  1.54  1.06, 2.24  Abbreviations: CI, confidence interval; DOHMH, Department of Health and Mental Hygiene; RR, relative risk; TB, tuberculosis. a RRs and 95% CIs were estimated using a modified Poisson regression model with a log-link and a robust sandwich variance estimator. b Dashes indicate characteristics that were not statistically associated with having a potential source case identified in the unadjusted analysis and therefore were not included in the adjusted modified Poisson regression model. c Includes children born in the United States and its territories. d Numbers may not sum to totals because of missing data. e Percentage of the population in a child’s United Hospital Fund neighborhood with a household income below the federal poverty threshold (low (<10% of residents below poverty limit), medium (10%–19.9%), high (20%–29.9%), or very high (≥30%)). View Large Age at reporting, neighborhood TB incidence, neighborhood population density, and neighborhood poverty level remained significantly associated with identification of a potential source case in the adjusted model. Children who resided in neighborhoods with medium or high TB incidence (relative risk = 1.73 (95% confidence interval: 1.35, 2.20) and relative risk = 1.62 (95% confidence interval: 1.26, 2.06), respectively) or in neighborhoods with ≥10% of residents living below the federal poverty limit had the highest risk of having a potential source case identified when compared with those living in neighborhoods with a low TB incidence or low poverty, respectively (Table 2). DISCUSSION Analyzing reports of young children with LTBI by demographic characteristics and by distance from known infectious TB cases at the time of LTBI diagnosis revealed patterns about the burden of LTBI in NYC, as well as locations where TB transmission may have been missed using standard TB control practices. Among the 1,717 children reported to DOHMH with LTBI during 2006–2012, the majority (64%) were born in the United States. This finding differs from previous research among young children in low-TB-incidence countries where foreign birth has been consistently identified as a risk factor for LTBI (21–25). The deviation from this trend in our study, when combined with the young average age of the children (2.9 years), indicate that recent transmission of M. tuberculosis may still be happening in NYC despite decreases in TB rates for over 2 decades. Though information on foreign travel (21, 23–25) and parental country of birth (26) was not available for analysis in the present investigation, these factors may serve as important modifiers of this relationship and should be explored in future research. While the demographic characteristics of children with LTBI suggest that local TB transmission may have occurred, we also employed geospatial tools to find potential source cases for children. This process differs from a standard associate investigation in that it finds potential source cases who may have infected a young child with TB through close proximity regardless of known exposure, instead of searching for TB patients who infected a young child with TB through household or close contact (12). While it was not an active case-finding technique, this approach offered an efficient alternative for detecting patients who potentially transmitted TB to young children. The importance of exploring new methods to efficiently uncover ongoing TB transmission at the local level was underscored by the low yield (35%) of source-case and cluster investigations on the 72 children diagnosed with active TB disease during the study period. This is an important consideration for underresourced TB control programs. This geospatial method found a potential source case for almost all children with a valid address who were not known to have contact with a TB case (92%). Interestingly, the proportion of children with a potential source case identified decreased significantly across the study period. This pattern mirrors the steady declines observed in the number and rate of children reported to DOHMH with LTBI. The current analysis did not identify the drivers behind these reductions (e.g., changes in testing for LTBI, declines in knowledge of reporting requirements, or actual decreases in numbers of children with LTBI), and future investigations should examine these trends further. Among the potential source-case matches identified, assessment of risk factors enabled us to evaluate elements associated with potential TB transmission in NYC. For example, 27 children lived in the same residential building as a TB case; none of these children had documented contact with a TB patient, and most had been born in the United States (78%). Given that these children were in general a low-risk group for LTBI (24, 25), these matches provide strong evidence for local, recent TB transmission. However, this study was not equipped to characterize the mechanism of TB transmission to young children. Though it is considered rare, children may have been infected through casual contact with a TB patient in their residential building, an event which has been documented in previous investigations (27, 28). Alternatively, these children may have been in contact with a TB patient who did not name them during contact investigations. Both situations highlight limitations of core TB control methods, which depend on TB patients to recall and report contacts (13), and thereby the need for novel ways to detect transmission to high-risk groups. Monitoring reports of LTBI in young children to identify those living in the same building as a recent TB patient could be an important mechanism for uncovering sites where TB transmission may be happening and thus TB patients who may require a more in-depth contact investigation. On a broader scale, geographic and multivariate analysis provided insight into communities where transmission may be ongoing. Children living in neighborhoods with a high TB incidence, ≥50,000 persons per square mile, or more than 10% of the population living below the federal poverty limit were more likely to have a potential source case identified. On an individual level, children who lived in buildings with more than 1 family also had greater risk of source-case identification in the bivariate analysis. These results align with knowledge of TB transmission dynamics, in which crowding, urban dwelling, and residence in high-incidence areas are consistently recognized as social determinants of exposure to M. tuberculosis (29). Therefore, as expected, potential transmission of TB in NYC was associated with living in high-risk neighborhoods and buildings. This finding helps inform DOHMH control and prevention efforts. While resources may not allow for case management of every child under age 5 with LTBI reported in NYC, knowledge of local epidemiology and use of spatial analysis tools can help to prioritize children with a potential source case in NYC. For example, TB surveillance data could be used to identify young children reported with LTBI who live in the same residential building as a recent TB patient. These matches may signal the need for the TB control program to conduct a more through contact investigation of the patient with active TB disease. These efforts may help to yield additional missed contacts eligible for testing and treatment for LTBI or TB disease. These monitoring methods can also help identify regions or pockets with potential TB transmission and consequently areas that may require outreach to prevent future TB cases, especially among this young and high-risk population. This study was not without limitations. Underreporting of LTBI in young children by NYC health-care providers probably occurred, and it is difficult to predict how this bias may have affected the results. Children may also have been infected with TB prior to the identification and treatment of their potential source-case match, and consequently some matches may not have represented recent local transmission. Furthermore, the data for this investigation were collected in the course of routine TB control activities and therefore were not gathered for research purposes. Given that children reported to have a positive test for TB infection do not receive case management from DOHMH staff, demographic and clinical data (including chest radiograph results) were missing for some children. As a result, complete information about risk factors, such as parents’ country of birth (26), foreign travel (21, 23–25), and time spent in congregate settings such as day-care centers or hospitals, was not available for analysis. While knowledge of these variables would enrich the understanding of risk factors, comprehensive information on children’s neighborhoods and residential buildings still provided a unique and detailed view on regions where transmission may occur. Finally, there has been a lack of data investigating the sensitivity and specificity of interferon-γ release assay tests in children under 5 years of age, and Centers for Disease Control and Prevention guidance recommends tuberculin skin tests as the preferred test for this age group (30). The children described in this investigation were tested with both tuberculin skin tests and interferon-γ release assays, and we are unable to project how this influenced the results, although the vast majority (98%) were tested using tuberculin skin tests. Additionally, false-positive test results are possible, since children with LTBI who were born in the United States had unknown risk factors for targeted TB infection testing and children with LTBI who were born outside of the United States may have received Bacillus Calmette-Guérin immunization (12). In conclusion, this evaluation provided important insights into the burden of LTBI among young children in NYC and demonstrated innovative use of LTBI surveillance data in pursuit of the goal of TB elimination. A number of findings from this investigation, such as the high proportion of children with LTBI born in the United States and the 27 children who lived in the same building as an infectious TB case, indicate that undetected TB transmission may be occurring in NYC. Potential TB transmission, defined as a match between a potential source case and a child with LTBI, was associated with residence in neighborhoods and buildings with high population density, poverty, and TB incidence. Examination of reports of LTBI in young children could be used as a method for DOHMH to locate buildings or regions where TB transmission may have occurred and subsequently TB patients who might require additional contact investigation or areas for targeting outreach to providers about testing, treating, and reporting LTBI among young children. These efforts would help to prevent TB disease in this sentinel population. ACKNOWLEDGMENTS Author affiliations: Centers for Disease Control and Prevention/Council of State and Territorial Epidemiologists Applied Epidemiology Fellowship Program, Atlanta, Georgia (Jennifer Sanderson Slutsker); and New York City Department of Health and Mental Hygiene, Long Island City, New York (Jennifer Sanderson Slutsker, Lisa Trieu, Aldo Crossa, Shama Desai Ahuja). J.S.S. was supported by an appointment to the Applied Epidemiology Fellowship Program, which is administered by the Council of State and Territorial Epidemiologists and funded by the Centers for Disease Control and Prevention (cooperative agreement 1U380T000143-01). We acknowledge field and surveillance staff from the Bureau of Tuberculosis Control, New York City Department of Health and Mental Hygiene, for their contribution to data collection. This project has been presented in oral or poster sessions at the International Conference on Emerging Infectious Diseases, Atlanta, Georgia (August 24–26, 2015); the Council of State and Territorial Epidemiologists Annual Conference, Boston, Massachusetts (June 14–18, 2015); the National Tuberculosis Conference, Atlanta, Georgia (June 8–11, 2015); and the New York City Epidemiology Forum, New York, New York (February 27, 2015). Conflict of interest: none declared. 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American Journal of EpidemiologyOxford University Press

Published: Nov 8, 2017

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