Pfizer-BioNTech Coronavirus Disease 2019 Vaccine Effectiveness Against Severe Acute Respiratory Syndrome Coronavirus 2 Infection Among Long-term Care Facility Staff With and Without Prior Infection in New York City, January-June 2021.

BACKGROUND: Evidence is accumulating of coronavirus disease 2019 (COVID-19) vaccine effectiveness among persons with prior severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. METHODS: We evaluated the effect against incident SARS-CoV-2 infection of (1) prior infection without vaccination, (2) vaccination (2 doses of Pfizer-BioNTech COVID-19 vaccine) without prior infection, and (3) vaccination after prior infection, all compared with unvaccinated persons without prior infection. We included long-term care facility staff in New York City aged <65 years with weekly SARS-CoV-2 testing from 21 January to 5 June 2021. Test results were obtained from state-mandated laboratory reporting. Vaccination status was obtained from the Citywide Immunization Registry. Cox proportional hazards models adjusted for confounding with inverse probability of treatment weights. RESULTS: Compared with unvaccinated persons without prior infection, incident SARS-CoV-2 infection risk was lower in all groups: 54.6% (95% confidence interval, 38.0%-66.8%) lower among unvaccinated, previously infected persons; 80.0% (67.6%-87.7%) lower among fully vaccinated persons without prior infection; and 82.4% (70.8%-89.3%) lower among persons fully vaccinated after prior infection. CONCLUSIONS: Two doses of Pfizer-BioNTech COVID-19 vaccine reduced SARS-CoV-2 infection risk by ≥80% and, for those with prior infection, increased protection from prior infection alone. These findings support recommendations that all eligible persons, regardless of prior infection, be vaccinated against COVID-19.

Comparative hospitalization risk for SARS-CoV-2 Omicron and Delta variant infections, by variant predominance periods and patient-level sequencing results, New York City, August 2021-January 2022.

BACKGROUND: Comparing disease severity between SARS-CoV-2 variants among populations with varied vaccination and infection histories can help characterize emerging variants and support healthcare system preparedness. METHODS: We compared COVID-19 hospitalization risk among New York City residents with positive laboratory-based SARS-CoV-2 tests when ≥98% of sequencing results were Delta (August-November 2021) or Omicron (BA.1 and sublineages, January 2022). A secondary analysis defined variant exposure using patient-level sequencing results during July 2021-January 2022, comprising 1-18% of weekly confirmed cases. RESULTS: Hospitalization risk was lower among patients testing positive when Omicron (16,025/488,053, 3.3%) than when Delta predominated (8268/158,799, 5.2%). In multivariable analysis adjusting for demographic characteristics and prior diagnosis and vaccination status, patients testing positive when Omicron predominated, compared with Delta, had 0.72 (95% CI: 0.63, 0.82) times the hospitalization risk. In a secondary analysis of patients with sequencing results, hospitalization risk was similar among patients infected with Omicron (2042/29,866, 6.8%), compared with Delta (1780/25,272, 7.0%), and higher among the subset who received two mRNA vaccine doses (adjusted relative risk 1.64; 95% CI: 1.44, 1.87). CONCLUSIONS: Hospitalization risk was lower among patients testing positive when Omicron predominated, compared with Delta. This finding persisted after adjusting for prior diagnosis and vaccination status, suggesting intrinsic virologic properties, not population-based immunity, explained the lower severity. Secondary analyses demonstrated collider bias from the sequencing sampling frame changing over time in ways associated with disease severity. Representative data collection is necessary to avoid bias when comparing disease severity between previously dominant and newly emerging variants.

Contact tracing reveals community transmission of COVID-19 in New York City.

Understanding SARS-CoV-2 transmission within and among communities is critical for tailoring public health policies to local context. However, analysis of community transmission is challenging due to a lack of high-resolution surveillance and testing data. Here, using contact tracing records for 644,029 cases and their contacts in New York City during the second pandemic wave, we provide a detailed characterization of the operational performance of contact tracing and reconstruct exposure and transmission networks at individual and ZIP code scales. We find considerable heterogeneity in reported close contacts and secondary infections and evidence of extensive transmission across ZIP code areas. Our analysis reveals the spatial pattern of SARS-CoV-2 spread and communities that are tightly interconnected by exposure and transmission. We find that locations with higher vaccination coverage and lower numbers of visitors to points-of-interest had reduced within- and cross-ZIP code transmission events, highlighting potential measures for curtailing SARS-CoV-2 spread in urban settings.

Contact tracing reveals community transmission of COVID-19 in New York City.

Understanding SARS-CoV-2 transmission within and among communities is critical for tailoring public health policies to local context. However, analysis of community transmission is challenging due to a lack of high-resolution surveillance and testing data. Here, using contact tracing records for 644,029 cases and their contacts in New York City during the second pandemic wave, we provide a detailed characterization of the operational performance of contact tracing and reconstruct exposure and transmission networks at individual and ZIP code scales. We find considerable heterogeneity in reported close contacts and secondary infections and evidence of extensive transmission across ZIP code areas. Our analysis reveals the spatial pattern of SARS-CoV-2 spread and communities that are tightly interconnected by exposure and transmission. We find that higher vaccination coverage and reduced numbers of visitors to points-of-interest are associated with fewer within- and cross-ZIP code transmission events, highlighting potential measures for curtailing SARS-CoV-2 spread in urban settings.

Tuberculosis Contact Investigations Conducted in New York City Adult Day Care and Senior Centers, 2011-2018.

OBJECTIVES: Multiple tuberculosis (TB) exposures have been reported in New York City (NYC) adult day care and senior centers. Strategies to identify TB transmission at such locations are needed. METHOD: Review of the NYC TB Registry identified 12 contact investigations (CIs) at adult day care or senior centers (2011-2018). RESULTS: Median age of the 12 index patients was 81 years. Of 148 contacts identified who had no history of TB infection or disease, 141 (95%) were tested for TB, primarily with interferon gamma release assays; 46 (33%) tested positive. Transmission was probable (n = 3) or possible (n = 1) at 4 (33%) centers; at all of these, the index patient had an acid-fast bacilli-positive sputum smear. Transmission was not found from index patients with negative sputum smears. DISCUSSION: We found evidence of transmission of smear-positive respiratory TB disease to contacts in adult day care or senior centers, underscoring the importance of CI.

Factors Associated With Sputum Culture-Negative vs Culture-Positive Diagnosis of Pulmonary Tuberculosis.

Importance: Recognition of active tuberculosis (TB) in its earliest stages could reduce morbidity and prevent advancement to transmissible disease. Little is published about the occurrence and presentation of sputum culture-negative pulmonary TB (PTB), an early paucibacillary but often underrecognized disease state. Objective: To assess differences between culture-negative and culture-positive PTB regarding occurrence, clinical presentation, radiographic findings, demographics, and comorbidities. Design, Setting, and Participants: Cross-sectional study in which surveillance data of adult patients with PTB reported to the New York City Department of Health in New York, New York, from 2011 through 2013, ie, years for which demographic, clinical, and radiographic data were collected. Patients were aged 18 years or older, had signs of pulmonary disease, and had mycobacterial sputum culture results; those with HIV coinfection or a TB diagnosis within 2 years prior to presentation were excluded. Culture-negative PTB was defined as clinical and radiographic presentation consistent with TB, 3 negative results on sputum culture, and improvement with antituberculous treatment. The analyses were performed between 2015 and 2016; notably, the proportion of reported patients with culture-negative PTB has remained consistent during the past 2 decades. Main Outcomes and Measures: The occurrence of culture-negative PTB among all patients with PTB was calculated, and demographics, comorbidities, symptoms, and radiographic findings were compared between culture-negative and culture-positive PTB. Results: Of the 796 patients with PTB (median [interquartile range] age, 41 [29-54] years; 499 [63%] men) who met criteria for analysis, 116 (15%) had negative results on sputum culture. Patients with culture-negative PTB compared with culture-positive PTB were less frequently male (53% vs 64%; P = .03) and presented with a significantly lower frequency of cough (68% vs 89%; P < .001), weight loss (39% vs 51%; P = .03), and cavitation on both chest radiograph (7% vs 28%; P < .001) and chest computed tomographic scan (26% vs 59%; P < .001). Conclusions and Relevance: Given the lack of criterion-standard test confirmation and the relative paucity of symptoms and radiological abnormalities, culture-negative PTB is likely underdiagnosed and its occurrence underestimated globally. Awareness of these findings, enhanced diagnostic approaches, and, ideally, better biomarkers could improve detection and treatment of this early disease and reduce the development of transmissible TB.

Towards better prediction of Mycobacterium tuberculosis lineages from MIRU-VNTR data.

The determination of lineages from strain-based molecular genotyping information is an important problem in tuberculosis. Mycobacterial interspersed repetitive unit-variable number tandem repeat (MIRU-VNTR) typing is a commonly used molecular genotyping approach that uses counts of the number of times pre-specified loci repeat in a strain. There are three main approaches for determining lineage based on MIRU-VNTR data - one based on a direct comparison to the strains in a curated database, and two others, on machine learning algorithms trained on a large collection of labeled data. All existing methods have limitations. The direct approach imposes an arbitrary threshold on how much a database strain can differ from a given one to be informative. On the other hand, the machine learning-based approaches require a substantial amount of labeled data. Notably, all three methods exhibit suboptimal classification accuracy without additional data. We explore several computational approaches to address these limitations. First, we show that eliminating the arbitrary threshold improves the performance of the direct approach. Second, we introduce RuleTB, an alternative direct method that proposes a concise set of rules for determining lineages. Lastly, we propose StackTB, a machine learning approach that requires only a fraction of the training data to outperform the accuracy of both existing machine learning methods. Our approaches demonstrate superior performance on a training dataset collected in New York City over 10 years, and the improvement in performance translates to a held-out testing set. We conclude that our methods provide opportunities for improving the determination of pathogenic lineages based on MIRU-VNTR data.

Treatment correlates of successful outcomes in pulmonary multidrug-resistant tuberculosis: an individual patient data meta-analysis.

BACKGROUND: Treatment outcomes for multidrug-resistant tuberculosis remain poor. We aimed to estimate the association of treatment success and death with the use of individual drugs, and the optimal number and duration of treatment with those drugs in patients with multidrug-resistant tuberculosis. METHODS: In this individual patient data meta-analysis, we searched MEDLINE, Embase, and the Cochrane Library to identify potentially eligible observational and experimental studies published between Jan 1, 2009, and April 30, 2016. We also searched reference lists from all systematic reviews of treatment of multidrug-resistant tuberculosis published since 2009. To be eligible, studies had to report original results, with end of treatment outcomes (treatment completion [success], failure, or relapse) in cohorts of at least 25 adults (aged >18 years). We used anonymised individual patient data from eligible studies, provided by study investigators, regarding clinical characteristics, treatment, and outcomes. Using propensity score-matched generalised mixed effects logistic, or linear regression, we calculated adjusted odds ratios and adjusted risk differences for success or death during treatment, for specific drugs currently used to treat multidrug-resistant tuberculosis, as well as the number of drugs used and treatment duration. FINDINGS: Of 12 030 patients from 25 countries in 50 studies, 7346 (61%) had treatment success, 1017 (8%) had failure or relapse, and 1729 (14%) died. Compared with failure or relapse, treatment success was positively associated with the use of linezolid (adjusted risk difference 0·15, 95% CI 0·11 to 0·18), levofloxacin (0·15, 0·13 to 0·18), carbapenems (0·14, 0·06 to 0·21), moxifloxacin (0·11, 0·08 to 0·14), bedaquiline (0·10, 0·05 to 0·14), and clofazimine (0·06, 0·01 to 0·10). There was a significant association between reduced mortality and use of linezolid (-0·20, -0·23 to -0·16), levofloxacin (-0·06, -0·09 to -0·04), moxifloxacin (-0·07, -0·10 to -0·04), or bedaquiline (-0·14, -0·19 to -0·10). Compared with regimens without any injectable drug, amikacin provided modest benefits, but kanamycin and capreomycin were associated with worse outcomes. The remaining drugs were associated with slight or no improvements in outcomes. Treatment outcomes were significantly worse for most drugs if they were used despite in-vitro resistance. The optimal number of effective drugs seemed to be five in the initial phase, and four in the continuation phase. In these adjusted analyses, heterogeneity, based on a simulated I2 method, was high for approximately half the estimates for specific drugs, although relatively low for number of drugs and durations analyses. INTERPRETATION: Although inferences are limited by the observational nature of these data, treatment outcomes were significantly better with use of linezolid, later generation fluoroquinolones, bedaquiline, clofazimine, and carbapenems for treatment of multidrug-resistant tuberculosis. These findings emphasise the need for trials to ascertain the optimal combination and duration of these drugs for treatment of this condition. FUNDING: American Thoracic Society, Canadian Institutes of Health Research, US Centers for Disease Control and Prevention, European Respiratory Society, Infectious Diseases Society of America.

Comparison of different treatments for isoniazid-resistant tuberculosis: an individual patient data meta-analysis.

BACKGROUND: Isoniazid-resistant, rifampicin-susceptible (INH-R) tuberculosis is the most common form of drug resistance, and is associated with failure, relapse, and acquired rifampicin resistance if treated with first-line anti-tuberculosis drugs. The aim of the study was to compare success, mortality, and acquired rifampicin resistance in patients with INH-R pulmonary tuberculosis given different durations of rifampicin, ethambutol, and pyrazinamide (REZ); a fluoroquinolone plus 6 months or more of REZ; and streptomycin plus a core regimen of REZ. METHODS: Studies with regimens and outcomes known for individual patients with INH-R tuberculosis were eligible, irrespective of the number of patients if randomised trials, or with at least 20 participants if a cohort study. Studies were identified from two relevant systematic reviews, an updated search of one of the systematic reviews (for papers published between April 1, 2015, and Feb 10, 2016), and personal communications. Individual patient data were obtained from authors of eligible studies. The individual patient data meta-analysis was performed with propensity score matched logistic regression to estimate adjusted odds ratios (aOR) and risk differences of treatment success (cure or treatment completion), death during treatment, and acquired rifampicin resistance. Outcomes were measured across different treatment regimens to assess the effects of: different durations of REZ (≤6 months vs >6 months); addition of a fluoroquinolone to REZ (fluoroquinolone plus 6 months or more of REZ vs 6 months or more of REZ); and addition of streptomycin to REZ (streptomycin plus 6 months of rifampicin and ethambutol and 1-3 months of pyrazinamide vs 6 months or more of REZ). The overall quality of the evidence was assessed using GRADE methodology. FINDINGS: Individual patient data were requested for 57 cohort studies and 17 randomised trials including 8089 patients with INH-R tuberculosis. We received 33 datasets with 6424 patients, of which 3923 patients in 23 studies received regimens related to the study objectives. Compared with a daily regimen of 6 months of (H)REZ (REZ with or without isoniazid), extending the duration to 8-9 months had similar outcomes; as such, 6 months or more of (H)REZ was used for subsequent comparisons. Addition of a fluoroquinolone to 6 months or more of (H)REZ was associated with significantly greater treatment success (aOR 2·8, 95% CI 1·1-7·3), but no significant effect on mortality (aOR 0·7, 0·4-1·1) or acquired rifampicin resistance (aOR 0·1, 0·0-1·2). Compared with 6 months or more of (H)REZ, the standardised retreatment regimen (2 months of streptomycin, 3 months of pyrazinamide, and 8 months of isoniazid, rifampicin, and ethambutol) was associated with significantly worse treatment success (aOR 0·4, 0·2-0·7). The quality of the evidence was very low for all outcomes and treatment regimens assessed, owing to the observational nature of most of the data, the diverse settings, and the imprecision of estimates. INTERPRETATION: In patients with INH-R tuberculosis, compared with treatment with at least 6 months of daily REZ, addition of a fluoroquinolone was associated with better treatment success, whereas addition of streptomycin was associated with less treatment success; however, the quality of the evidence was very low. These results support the conduct of randomised trials to identify the optimum regimen for this important and common form of drug-resistant tuberculosis. FUNDING: World Health Organization and Canadian Institutes of Health Research.

Contemporary Social Disparities in TB Infection and Disease in the USA: a Review.

PURPOSE OF REVIEW: Socioeconomic status (SES) has long been understood to be a key determinant of the distribution of tuberculosis (TB), and the role of social factors has long been a truism of TB epidemiology. We review studies that have examined the social determinants of TB in the USA in the past 20 years. We pay particular attention to how the findings of these studies fit within the framework of fundamental cause theory and argue that a more explicit linkage with fundamental cause theory is critical for understanding the current state of TB health disparities in the USA and for charting a way towards TB elimination in the USA. RECENT FINDINGS AND SUMMARY: Our review finds that while in the past 20 years there have been studies that have documented the ongoing association between social factors and TB disease in the USA, few studies explore the precise mechanisms through which social factors continue to influence TB patterns. We advocate for a move towards a system-based approach both in theory development and analyses, allowing for the incorporation of more complex social dynamics to address long-standing disparities in TB disease.

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

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.

Current and future trends in tuberculosis incidence in New York City: a dynamic modelling analysis.

BACKGROUND: After steady decline since the 1990s, tuberculosis (TB) incidence in New York City (NYC) and the United States (US) has flattened. The reasons for this trend and the implications for the future trajectory of TB in the US remain unclear. METHODS: We developed a compartmental model of TB in NYC, parameterized with detailed epidemiological data. We ran the model under five alternative scenarios representing different explanations for recent declines in TB incidence. We evaluated each scenario's relative likelihood by comparing its output to available data. We used the most likely scenarios to explore drivers of TB incidence and predict future trajectories of the TB epidemic in NYC. FINDINGS: Demographic changes and declining TB transmission alone were insufficient to explain recent trends in NYC TB incidence. Only scenarios that assumed contemporary changes in TB dynamics among the foreign-born - a declining rate of reactivation or a decrease in imported subclinical TB - could accurately describe the trajectory of TB incidence since 2007. In those scenarios, the projected decline in TB incidence from 2015 to 2025 varied from minimal [2·0%/year (95% credible interval 0·4-3·5%)] to similar to 2005 to 2009 trends [4·4%/year (2·5-6·4%)]. The primary factor differentiating optimistic from pessimistic projections was the degree to which improvements in TB dynamics among the foreign-born continued into the coming decade. INTERPRETATION: Further progress against TB in NYC requires additional focus on the foreign-born population. Absent additional intervention in this group, TB incidence may not decline further.

Epidemiology of Pediatric Multidrug-Resistant Tuberculosis in the United States, 1993-2014.

BACKGROUND: Multidrug-resistant tuberculosis (MDR-TB) is an important global public health threat, but accurate estimates of MDR-TB burden among children are lacking. METHODS: We analyzed demographic, clinical, and laboratory data for newly diagnosed pediatric (age <15 years) TB cases reported to the US National TB Surveillance System during 1993-2014. MDR-TB was defined as culture-confirmed TB disease with resistance to at least isoniazid and rifampicin. To ascertain potential underestimation of pediatric MDR-TB, we surveyed high-burden states for clinically diagnosed cases treated for MDR-TB. RESULTS: Of 20789 pediatric TB cases, 5162 (24.8%) had bacteriologically confirmed TB. Among 4826 (93.5%) with drug susceptibility testing, 82 (1.7%) had MDR-TB. Most pediatric MDR-TB cases were female (n = 51 [62%]), median age was 5 years (interquartile range, 1-12 years), one-third were Hispanic (n = 28 [34%]), and two-thirds (n = 55 [67%]) were born in the United States. Most cases had additional resistance to ≥1 other first-line drug (n = 66 [81%]) and one-third had resistance to ≥1 second-line drug (24/73 tested). Of 77 who started treatment prior to 2013, 66 (86%) completed treatment and 4 (5%) died. Among the 4 high-TB-burden states/jurisdictions surveyed, there was 42%-55% underestimation of pediatric MDR-TB cases when using only culture-confirmed case definitions. CONCLUSIONS: Only one-quarter of pediatric TB cases had culture-confirmed TB, likely resulting in underestimation of true pediatric MDR-TB burden in the United States using strictly bacteriologic criteria. Better estimates of pediatric MDR-TB burden in the United States are needed and should include clinical diagnoses based on epidemiologic criteria.

Group 5 drugs for multidrug-resistant tuberculosis: individual patient data meta-analysis.

The role of so-called "group 5" second-line drugs as a part of antibiotic therapy for multidrug-resistant tuberculosis (MDR-TB) is widely debated. We performed an individual patient data meta-analysis to evaluate the effectiveness of several group 5 drugs including amoxicillin/clavulanic acid, thioacetazone, the macrolide antibiotics, linezolid, clofazimine and terizidone for treatment of patients with MDR-TB.Detailed individual patient data were obtained from 31 published cohort studies of MDR-TB therapy. Pooled treatment outcomes for each group 5 drug were calculated using a random effects meta-analysis. Primary analyses compared treatment success to a combined outcome of failure, relapse or death.Among 9282 included patients, 2191 received at least one group 5 drug. We found no improvement in treatment success among patients taking clofazimine, amoxicillin/clavulanic acid or macrolide antibiotics, despite applying a number of statistical approaches to control confounding. Thioacetazone was associated with increased treatment success (OR 2.6, 95% CI 1.1-6.1) when matched controls were selected from studies in which the group 5 drugs were not used at all, although this result was heavily influenced by a single study.The development of more effective antibiotics to treat drug-resistant TB remains an urgent priority.

Diabetes Among People With Tuberculosis, HIV Infection, Viral Hepatitis B and C, and STDs in New York City, 2006-2010.

Matching infectious disease surveillance data has become a routine activity for many health departments. With the increasing focus on chronic disease, it is also useful to explore opportunities to match infectious and chronic disease surveillance data. To understand the burden of diabetes in New York City (NYC), adults with select infectious diseases (tuberculosis, HIV infection, hepatitis B, hepatitis C, chlamydial infection, gonorrhea, and syphilis) reported between 2006 and 2010 were matched with hemoglobin A1c results reported in the same period. Persons were considered to have diabetes with 2 or more hemoglobin A1c test results of 6.5% or higher. The analysis was restricted to persons who were 18 years or older at the time of first report, either A1c or infectious disease. Overall age-adjusted diabetes prevalence was 8.1%, and diabetes prevalence was associated with increasing age; among NYC residents, prevalence ranged from 0.6% among 18- to 29-year-olds to 22.4% among those 65 years and older. This association was also observed in each infectious disease. Diabetes prevalence was significantly higher among persons with tuberculosis born in Mexico, Jamaica, Honduras, Guyana, Bangladesh, Dominican Republic, the Philippines, and Haiti compared with those born in the United States after adjusting for age and sex. Hepatitis C virus-infected women had higher age-adjusted prevalence of diabetes compared with the NYC population as a whole. Recognizing associations between diabetes and infectious diseases can assist early diagnosis and management of these conditions. Matching chronic disease and infectious disease surveillance data has important implications for local health departments and large health system practices, including increasing opportunities for integrated work both internal to systems and with the local community. Large health systems may consider opportunities for increased collaboration across infectious and chronic disease programs facilitated through data linkages of routinely collected surveillance data.

Long-term Mortality of Patients With Tuberculous Meningitis in New York City: A Cohort Study.

Background: Tuberculous meningitis (TBM) is the most devastating clinical presentation of infection with Mycobacterium tuberculosis; delayed initiation of effective antituberculosis therapy is associated with poor treatment outcomes. Our objective was to determine the relationship between drug resistance and 10-year mortality among patients with TBM. Methods: We conducted a retrospective cohort study of 324 patients with culture-confirmed TBM, susceptibility results reported for isoniazid and rifampin, and initiation of at least 2 antituberculosis drugs, reported to the tuberculosis registry in New York City between 1 January 1992 and 31 December 2001. Date of death was ascertained by matching the tuberculosis registry with death certificate data for 1992-2012 from the New York Office of Vital Statistics. Human immunodeficiency virus (HIV) status was ascertained by medical records review, matching with the New York City HIV Surveillance registry, and review of cause of death. Results: Among 257 TBM patients without rifampin-resistant isolates, isoniazid resistance was associated with mortality after the first 60 days of treatment when controlling for age and HIV infection (adjusted hazard ratio, 1.94 [95% confidence interval, 1.08-3.94]). Death occurred before completion of antituberculosis therapy in 63 of 67 TBM patients (94%) with rifampin-resistant disease. Conclusions: Among patients with culture-confirmed TBM, we observed rapid early mortality in patients with rifampin-resistant isolates, and an independent association between isoniazid-resistant isolates and death after 60 days of therapy. These findings support the continued evaluation of rapid diagnostic techniques and the empiric addition of second-line drugs for patients with clinically suspected drug-resistant TBM.

Contact Investigations Around Mycobacterium tuberculosis Patients Without Positive Respiratory Culture.

OBJECTIVE: To evaluate the yield and effectiveness of contact investigations conducted around potentially infectious tuberculosis (TB) patients with no positive respiratory culture for Mycobacterium tuberculosis in New York City (NYC). DESIGN: All TB patients without a positive respiratory culture from 2003 to 2012 were extracted from the NYC TB registry, and all patients eligible for contact investigation and their contacts were evaluated. Patients without a positive respiratory culture were defined as eligible for contact investigation if they had a respiratory nucleic acid amplification result positive for M tuberculosis, a cavitary chest radiograph, or a positive respiratory acid-fast bacilli smear. SETTING: NYC, New York. MAIN OUTCOME MEASURES: To evaluate the yield of the investigations, the number of contacts identified and the outcome of testing was quantified. Potential transmission was defined on the basis of whether active TB patients were detected among the contacts and if a contact had a TB test conversion. RESULTS: From 2003 to 2012, there were 2191 TB patients without a positive respiratory culture in NYC, 374 (17%) of which were considered eligible for contact investigation. A total of 11 096 contacts were identified around 300 (80%) eligible patients, 136 of whom had a diagnosis of TB infection; of those with TB infection who initiated preventive treatment, 66% completed treatment. Potential transmission was identified around 14 patients, with the identification of 2 additional cases of active TB and 15 contacts with TB infection test conversion. CONCLUSIONS: Conducting contact investigations around patients without a positive respiratory culture yielded evidence of possible transmission and led to the identification and treatment of new TB cases and those with TB infection. These findings suggest that these investigations should be conducted in settings where resources permit.

High Tuberculosis Strain Diversity Among New York City Public Housing Residents.

OBJECTIVES: We sought to better understand tuberculosis (TB) epidemiology among New York City Housing Authority (NYCHA) residents, after a recent TB investigation identified patients who had the same TB strain. METHODS: The study population included all New York City patients with TB confirmed during 2001 through 2009. Patient address at diagnosis determined NYCHA residence. We calculated TB incidence, reviewed TB strain data, and identified factors associated with TB clustering. RESULTS: During 2001 to 2009, of 8953 individuals in New York City with TB, 512 (6%) had a NYCHA address. Among the US-born, TB incidence among NYCHA residents (6.0/100,000 persons) was twice that among non-NYCHA residents (3.0/100,000 persons). Patients in NYCHA had high TB strain diversity. US birth, younger age, and substance use were associated with TB clustering among NYCHA individuals with TB. CONCLUSIONS: High TB strain diversity among residents of NYCHA with TB does not suggest transmission among residents. These findings illustrate that NYCHA's higher TB incidence is likely attributable to its higher concentration of individuals with known TB risk factors.

Epidemiologic Correlates of Pyrazinamide-Resistant Mycobacterium tuberculosis in New York City.

Pyrazinamide (PZA) has important sterilizing activity in tuberculosis (TB) chemotherapy. We describe trends, risk factors, and molecular epidemiology associated with PZA-resistant (PZA(r)) Mycobacterium tuberculosis in New York City (NYC). From 2001 to 2008, all incident culture-positive TB cases reported by the NYC Department of Health and Mental Hygiene (DOHMH) were genotyped by IS6110-based restriction fragment length polymorphism and spoligotype. Multidrug-resistant (MDR) isolates underwent DNA sequencing of resistance-determining regions of pncA, rpoB, katG, and fabG1. Demographic and clinical information were extracted from the NYC DOHMH TB registry. During this period, PZA(r) doubled (1.6% to 3.6%) overall, accounting for 44% (70/159) of the MDR population and 1.4% (75/5511) of the non-MDR population. Molecular genotyping revealed strong microbial phylogenetic associations with PZA(r). Clustered isolates and those from acid-fast bacillus (AFB) smear-positive cases had 2.7 (95% confidence interval [CI] = 1.71 to 4.36) and 2.0 (95% CI = 1.19 to 3.43) times higher odds of being PZA(r), respectively, indicating a strong likelihood of recent transmission. Among the MDR population, PZA(r) was acquired somewhat more frequently via primary transmission than by independent pathways. Our molecular analysis also revealed that several historic M. tuberculosis strains responsible for MDR TB outbreaks in the early 1990s were continuing to circulate in NYC. We conclude that the increasing incidence of PZA(r), with clear microbial risk factors, underscores the importance of routine PZA drug susceptibility testing and M. tuberculosis genotyping for the identification, control, and prevention of increasingly resistant organisms.

Increasing the efficiency and yield of a tuberculosis contact investigation through electronic data systems matching.

BACKGROUND: Electronic health data may improve the timeliness and accuracy of resource-intense contact investigations (CIs) in healthcare settings. METHODS: In September 2013, we initiated a CI around a healthcare worker (HCW) with infectious tuberculosis (TB) who worked in a maternity ward. Two sources of electronic health data were employed: hospital-based electronic medical records (EMRs), to identify patients exposed to the HCW, and an electronic immunization registry, to obtain contact information for exposed infants and their providers at two points during follow-up. RESULTS: Among 954 patients cared for in the maternity ward during the HCW's infectious period, the review of EMRs identified 285 patients (30%) who interacted with the HCW and were, thus, exposed to TB. Matching infants to the immunization registry offered new provider information for 52% and 30% of the infants in the first and second matches. Providers reported evaluation results for the majority of patients (66%). CONCLUSION: Data matching improved the efficiency and yield of this CI, thereby demonstrating the usefulness of enhancing CIs with electronic health data.