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.

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.

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.

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.

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.

Moxifloxacin Prophylaxis against MDR TB, New York, New York, USA.

Contacts of persons infected with multidrug-resistant tuberculosis (MDR TB) have few prophylaxis options. Of 50 contacts of HIV- and MDR TB-positive persons who were treated with moxifloxacin, 30 completed treatment and 3 discontinued treatment because of gastrointestinal symptoms. Moxifloxacin was generally well-tolerated; further research of its efficacy against MDR TB is needed.

Risk for Tuberculosis Disease Among Contacts with Prior Positive Tuberculin Skin Test: A retrospective Cohort Study, New York City.

BACKGROUND: Patients with prior positive tuberculin skin test (TST) results may benefit from prophylaxis after repeat exposure to infectious tuberculosis (TB). OBJECTIVE: To evaluate factors associated with active TB disease among persons with prior positive TST results named as contacts of persons with infectious TB. DESIGN: Population-based retrospective cohort study. PARTICIPANTS: A total of 2,933 contacts with prior positive TST results recently exposed to infectious TB identified in New York City's TB registry during the period from January 1, 1997 through December 31, 2003. MAIN MEASUREMENTS: Contacts developing active TB disease ≤ 4 years after exposure were identified and compared with those who did not, using Poisson regression analysis. Genotyping was performed on selected Mycobacterium tuberculosis-positive isolates. KEY RESULTS: Among contacts with prior positive TST results, 39 (1.3 %) developed active TB disease ≤ 4 years after exposure (≤ 2 years: 34). Risk factors for contacts that were independently associated with TB were age < 5 years (adjusted prevalence ratio [aPR] = 19.48; 95 % confidence interval [CI] = 7.15-53.09), household exposure (aPR = 2.60;CI = 1.30-5.21), exposure to infectious patients (i.e., cavities on chest radiograph, acid-fast bacilli on sputum smear; aPR = 1.9 3; CI = 1.01-3.71), and exposure to a U.S.-born index patient (aPR = 4.04; CI = 1.95-8.38). Receipt of more than 1 month of treatment for latent TB infection following the current contact investigation was found to be protective (aPR = 0.27; CI = .08-0.93). Genotype results were concordant with the index patients among 14 of 15 contacts who developed active TB disease and had genotyping results available. CONCLUSIONS: Concordant genotype results and a high proportion of contacts developing active TB disease within 2 years of exposure indicate that those with prior positive TST results likely developed active TB disease from recent rather than remote infection. Healthcare providers should consider prophylaxis for contacts with prior TB infection, especially young children and close contacts of TB patients (e.g., those with household exposure).

Estimated Prevalence of Tuberculosis Infection Among a New York City Clinic Population Using Interferon-gamma Release Assays.

BACKGROUND: Elimination of tuberculosis (TB) in the United States requires treating not only persons with active disease but also those infected with TB. Achieving this goal requires understanding local TB infection prevalence and identifying subgroups at increased risk for infection and disease. METHODS: The study population included all patients tested with an interferon-gamma release assay (IGRA) test at New York City (NYC) public TB clinics from October 1, 2006 to December 31, 2011. Patients who were not a case or contact at testing (general clinic patients) and who had a positive QuantiFERON-Gold In-Tube (QFT-GIT) test result were compared with those with indeterminate or negative results to identify characteristics associated with positive results. New York City TB surveillance data were used to identify clinic patients later diagnosed with active TB disease. RESULTS: A total of 69 273 IGRA tests were conducted. Among 20 066 patients tested with QFT-GIT, 16% tested positive, 83% tested negative, and <1% were indeterminate. Of 18 481 general clinic patients, 14% had a positive QFT-GIT result. Nine percent of United States-born patients compared with 19% of foreign-born patients had a positive result. Increasing age and birth in a high-incidence country were associated with a higher likelihood of having a positive result. One patient with a negative QFT-GIT result was identified as a TB case 2 years later. CONCLUSIONS: Using QFT-GIT data, the background prevalence of TB infection in NYC was estimated. Patient characteristics associated with a positive QFT-GIT result were consistent with known TB risk factors. Results suggest that IGRAs are reliable tests for TB infection.

Transmission of multidrug-resistant tuberculosis in the USA: a cross-sectional study.

BACKGROUND: Multidrug-resistant (MDR) tuberculosis is a potential threat to tuberculosis elimination, but the extent of MDR tuberculosis disease in the USA that is attributable to transmission within the country is unknown. We assessed transmission of MDR tuberculosis and potential contributing factors in the USA. METHODS: In a cross-sectional study, clinical, demographic, epidemiological, and Mycobacterium tuberculosis genotype data were obtained during routine surveillance of all verified cases of MDR tuberculosis reported from eight states in the USA (California from Jan 1, 2007, to Dec 31, 2009; Texas from Jan 1, 2007, to March 31, 2009; and the states of Colorado, Maryland, Massachusetts, New York, Tennessee, and Washington from Jan 1, 2007 to Dec 31, 2008). In-depth interviews and health-record abstraction were done for all who consented to ascertain potential interpersonal connections. FINDINGS: 168 cases of MDR tuberculosis were reported in the eight states during our study period. 92 individuals (55%) consented to in-depth interview. 20 (22%) of these individuals developed MDR tuberculosis as a result of transmission in the USA; a source case was identified for eight of them (9%). 20 individuals (22%) had imported active tuberculosis (ie, culture-confirmed disease within 3 months of entry into the USA). 38 (41%) were deemed to have reactivation of disease, of whom 14 (15%) had a known previous episode of tuberculosis outside the USA. Five individuals (5%) had documented treatment of a previous episode in the USA, and so were deemed to have relapsed. For nine cases (10%), insufficient evidence was available to definitively classify reason for presentation. INTERPRETATION: About a fifth of cases of MDR tuberculosis in the USA can be linked to transmission within the country. Many individuals acquire MDR tuberculosis before entry into the USA. MDR tuberculosis needs to be diagnosed rapidly to reduce potential infectious periods, and clinicians should consider latent tuberculosis infection treatment-tailored to the results of drug susceptibility testing of the putative source case-for exposed individuals. FUNDING: Centers for Disease Control and Prevention.

Using QuantiFERON-TB Gold In-Tube for field-based tuberculosis contact investigations in congregate settings.

Contact investigations are crucial to controlling tuberculosis in the United States. In these investigations, the tuberculin skin test has been the primary test to detect tuberculosis infection. Interferon-γ release assays, such as the QuantiFERON-TB Gold In-Tube test, were recently introduced and are intended to address limitations of the tuberculin skin test. However, there are limited data on the use of these tests in contact investigations in congregate settings. We present 2 field-based investigations to highlight potential advantages, limitations, and feasibility of using the QuantiFERON-TB Gold In-Tube test in congregate setting investigations.

Multidrug resistant pulmonary tuberculosis treatment regimens and patient outcomes: an individual patient data meta-analysis of 9,153 patients.

BACKGROUND: Treatment of multidrug resistant tuberculosis (MDR-TB) is lengthy, toxic, expensive, and has generally poor outcomes. We undertook an individual patient data meta-analysis to assess the impact on outcomes of the type, number, and duration of drugs used to treat MDR-TB. METHODS AND FINDINGS: Three recent systematic reviews were used to identify studies reporting treatment outcomes of microbiologically confirmed MDR-TB. Study authors were contacted to solicit individual patient data including clinical characteristics, treatment given, and outcomes. Random effects multivariable logistic meta-regression was used to estimate adjusted odds of treatment success. Adequate treatment and outcome data were provided for 9,153 patients with MDR-TB from 32 observational studies. Treatment success, compared to failure/relapse, was associated with use of: later generation quinolones, (adjusted odds ratio [aOR]: 2.5 [95% CI 1.1-6.0]), ofloxacin (aOR: 2.5 [1.6-3.9]), ethionamide or prothionamide (aOR: 1.7 [1.3-2.3]), use of four or more likely effective drugs in the initial intensive phase (aOR: 2.3 [1.3-3.9]), and three or more likely effective drugs in the continuation phase (aOR: 2.7 [1.7-4.1]). Similar results were seen for the association of treatment success compared to failure/relapse or death: later generation quinolones, (aOR: 2.7 [1.7-4.3]), ofloxacin (aOR: 2.3 [1.3-3.8]), ethionamide or prothionamide (aOR: 1.7 [1.4-2.1]), use of four or more likely effective drugs in the initial intensive phase (aOR: 2.7 [1.9-3.9]), and three or more likely effective drugs in the continuation phase (aOR: 4.5 [3.4-6.0]). CONCLUSIONS: In this individual patient data meta-analysis of observational data, improved MDR-TB treatment success and survival were associated with use of certain fluoroquinolones, ethionamide, or prothionamide, and greater total number of effective drugs. However, randomized trials are urgently needed to optimize MDR-TB treatment. Please see later in the article for the Editors' Summary.

Active case finding and prevention of tuberculosis among a cohort of contacts exposed to infectious tuberculosis cases in New York City.

BACKGROUND: Tuberculosis contact investigation identifies individuals who may be recently infected with tuberculosis and are thus at increased risk for disease. Contacts with latent tuberculosis infection (LTBI) are offered chemoprophylaxis to prevent active disease; however, the effectiveness of this intervention is unclear as treatment completion is generally low. METHODS: A retrospective cohort study of 30 561 contacts identified during investigation of 5182 cases of tuberculosis diagnosed in New York City, 1997-2003, was performed. We searched the NYC tuberculosis registry to identify contacts developing active tuberculosis within 4 years of follow-up. We estimated the following: number of contacts undergoing evaluation (ie, tuberculin skin test and/or chest radiograph) per prevalent case diagnosed; number of contacts with LTBI that need to be treated with standard chemoprophylaxis to prevent 1 active case. RESULTS: Of 30 561 contacts, 27 293 (89%) were evaluated and 268 prevalent cases were diagnosed (102 contacts evaluated per prevalent case diagnosed, 95% confidence interval [CI], 90-115). LTBI was diagnosed in 7597 contacts, including 6001 (79%) who initiated chemoprophylaxis, 3642 (61%) who later completed treatment, and 2359 (39%) who did not complete treatment. During 4 years of follow-up, active tuberculosis was diagnosed in 46 contacts with LTBI, including 22 of 6001 (0.4%) who initiated chemoprophylaxis and 24 of 1596 (1.5%) who did not initiate treatment. The absolute risk reduction afforded by chemoprophylaxis initiation was 1.1% (95% CI, .6%-1.9%), leading to an estimated 88 contacts treated to prevent 1 tuberculosis case (95% CI, 53-164). CONCLUSIONS: Contact investigation facilitates active case finding and tuberculosis prevention, even when completion rates of chemoprophylaxis are suboptimal.

Missed opportunities for tuberculosis prevention in New York City, 2003.

BACKGROUND: Proper management and prevention can radically decrease the incidence of tuberculosis (TB). To further decrease TB cases in New York City, every opportunity for prevention must be utilized. This study sought to identify patients whose disease could have been prevented and describe missed opportunities for TB prevention. METHODS: Patients diagnosed with TB from April to July, 2003 were identified using the New York City TB registry. Surveillance data, medical records, and patient interviews were used to determine whether patients missed a prevention opportunity or potential for screening. Preventable TB was defined as inappropriate screening of contacts and immigrants, inappropriate treatment of persons with prior TB diagnoses, or those who tested positive for latent TB infection (LTBI) as contacts, immigration, or in community settings. Potentially preventable TB was defined as occurring when those eligible for LTBI screening in community settings were not screened more than 1 year before TB diagnosis. Patients classified as having preventable or potentially preventable TB were grouped as patients with missed opportunities. We calculated the odds of missing a prevention opportunity using logistic regression. RESULTS: Among the 218 study patients, 22% had preventable TB and 35% had potentially preventable TB. The most common missed opportunity among patients with preventable TB was the failure to initiate LTBI treatment. Birth outside of the United States was not associated with missing a prevention opportunity (odds ratio [OR] = 1.31, confidence interval [CI] = 0.71-2.39); however, extended travel outside of the United States increased the odds (OR = 2.51, CI = 1.19-5.69), particularly among non-US-born patients (OR = 3.01, CI = 1.21-8.59). Missed screening opportunities related to pregnancy, employment, or school attendance were encountered by over half of the study patients. CONCLUSIONS: The majority of New York City TB patients in our cohort experienced at least 1 missed opportunity for prevention. Further study is warranted to determine whether LTBI treatment eligibility should be extended to those who travel for extended periods, particularly among the non-US-born patients.

Mycobacterium tuberculosis cluster with developing drug resistance, New York, New York, USA, 2003-2009.

In 2004, identification of patients infected with the same Mycobacterium tuberculosis strain in New York, New York, USA, resulted in an outbreak investigation. The investigation involved data collection and analysis, establishing links between patients, and forming transmission hypotheses. Fifty-four geographically clustered cases were identified during 2003-2009. Initially, the M. tuberculosis strain was drug susceptible. However, in 2006, isoniazid resistance emerged, resulting in isoniazid-resistant M. tuberculosis among 17 (31%) patients. Compared with patients with drug-susceptible M. tuberculosis, a greater proportion of patients with isoniazid-resistant M. tuberculosis were US born and had a history of illegal drug use. No patients named one another as contacts. We used patient photographs to identify links between patients. Three links were associated with drug use among patients infected with isoniazid-resistant M. tuberculosis. The photographic method would have been more successful if used earlier in the investigation. Name-based contact investigation might not identify all contacts, particularly when illegal drug use is involved.

Linezolid use for treatment of multidrug-resistant and extensively drug-resistant tuberculosis, New York City, 2000-06.

UNLABELLED: Rationale Linezolid may be effective for the treatment of multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB); however, serious adverse events are common and there is little information on the management of these toxicities. METHODS: We retrospectively reviewed public health and medical records of 16 MDR TB patients, including 10 patients with XDR TB, who were treated with linezolid in New York City between January 2000 and December 2006, to determine treatment outcomes and describe the incidence, management and predictors of adverse events. RESULTS: Linezolid was added to MDR TB regimens for a median duration of 16 months (range: 1-29). Eleven patients (69%) completed treatment, four (25%) died and one (6%) discontinued treatment without relapse. Myelosuppression occurred in 13 (81%) patients a median of 5 weeks (range: 1-11) after starting linezolid, gastrointestinal adverse events occurred in 13 (81%) patients after a median of 8 weeks (range: 1-57) and neurotoxicity occurred in seven (44%) patients after a median of 16 weeks (range: 10-111). Adverse events were managed by combinations of temporary suspension of linezolid, linezolid dose reduction and symptom management. Five (31%) patients required eventual discontinuation of linezolid. Myelosuppression was more responsive to clinical management strategies than was neurotoxicity. Leucopenia and neuropathy occurred more often in males and older age was associated with thrombocytopenia (P < 0.05). CONCLUSIONS: The majority of MDR TB patients on linezolid had favourable treatment outcomes, although treatment was complicated by adverse events that required extensive clinical management.

Population-based surveillance for Yersinia enterocolitica infections in FoodNet sites, 1996-1999: higher risk of disease in infants and minority populations.

Active surveillance for laboratory-confirmed Yersinia enterocolitica (YE) infections was conducted at 5 Foodborne Diseases Active Surveillance Network (FoodNet) sites in the United States during 1996-1999. The annual incidence averaged 0.9 cases/100,000 population. After adjusting for missing data, the average annual incidence by race/ethnicity was 3.2 cases/100,000 population among black persons, 1.5 cases/100,000 population among Asian persons, 0.6 cases/100,000 population among Hispanic persons, and 0.4 cases/100,000 population among white persons. Incidence increased with decreasing age in all race/ethnicity groups. Black infants had the highest incidence (141.9 cases/100,000 population; range, 8.7 cases/100,000 population in Minnesota to 207.0 cases/100,000 population in Georgia). Seasonal variations in incidence, with a marked peak in December, were noted only among black persons. YE infections should be suspected in black children with gastroenteritis, particularly during November-February. Culturing for YE should be part of routine testing of stool specimens by clinical laboratories serving populations at risk, especially during the winter months.

Egg consumption is the principal risk factor for sporadic Salmonella serotype Heidelberg infections: a case-control study in FoodNet sites.

To determine risk factors for sporadic Salmonella serotype Heidelberg diarrheal disease, we conducted a population-based case-control study in 5 Foodborne Diseases Active Surveillance Network (FoodNet) surveillance areas in 1996-1997. Forty-four case patients and 83 control subjects matched by age and telephone exchange were asked about exposures during the 5-day period before onset of illness in the case patient. Risk factors for infection were evaluated using conditional logistic regression analysis. Eating eggs prepared outside the home remained the only significant risk factor for illness (matched odds ratio [MOR], 6.0; 95% confidence interval [CI], 1.2-29.6). The population-attributable fraction of S. Heidelberg infections associated with eating eggs prepared outside the home was 37%. Eliminating the risk associated with out-of-home egg consumption could substantially reduce the incidence of S. Heidelberg infections. Control measures to prevent S. Heidelberg infection should include advising consumers to avoid eating undercooked eggs and educating food handlers about proper egg handling and cooking.