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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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).

Disparities in tuberculosis burden among South Asians living in New York City, 2001-2010.

OBJECTIVES: We have described the characteristics of South Asian-born tuberculosis (TB) patients living in New York City (NYC) and compared them with other foreign-born patients to explore possible explanations for the disproportionate burden of TB in the South Asian population. METHODS: We used data on demographic and clinical characteristics for TB patients identified by the NYC Bureau of Tuberculosis Control from 2001 to 2010 to compare South Asian patients with other Asian and other foreign-born patients. We reviewed genotyping and cluster investigation data for South Asian patients to assess the extent of genotype clustering and the possibility of local transmission in this population. RESULTS: The observed disparity in TB rates and burden among South Asians was not explained by social or clinical characteristics. A large amount of TB strain diversity was observed among South Asians, and they were less likely than other foreign-born patients to be infected with the same TB strain as another NYC patient. CONCLUSIONS: The majority of South Asians were likely infected with TB abroad. South Asians represent a meaningful foreign-born subpopulation for targeted detection and treatment of TB infection in NYC.

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.

Epidemiologic consequences of microvariation in Mycobacterium tuberculosis.

BACKGROUND: Evidence from genotype-phenotype studies suggests that genetic diversity in pathogens have clinically relevant manifestations that can impact outcome of infection and epidemiologic success. We studied 5 closely related Mycobacterium tuberculosis strains that collectively caused extensive disease (n = 862), particularly among US-born tuberculosis patients. METHODS: Representative isolates were selected using population-based genotyping data from New York City and New Jersey. Growth and cytokine/chemokine response were measured in infected human monocytes. Survival was determined in aerosol-infected guinea pigs. RESULTS: Multiple genotyping methods and phylogenetically informative synonymous single nucleotide polymorphisms showed that all strains were related by descent. In axenic culture, all strains grew similarly. However, infection of monocytes revealed 2 growth phenotypes, slower (doubling ∼55 hours) and faster (∼25 hours). The faster growing strains elicited more tumor necrosis factor α and interleukin 1ß than the slower growing strains, even after heat killing, and caused accelerated death of infected guinea pigs (∼9 weeks vs 24 weeks) associated with increased lung inflammation/pathology. Epidemiologically, the faster growing strains were associated with human immunodeficiency virus and more limited in spread, possibly related to their inherent ability to induce a strong protective innate immune response in immune competent hosts. CONCLUSIONS: Natural variation, with detectable phenotypic changes, among closely related clinical isolates of M. tuberculosis may alter epidemiologic patterns in human populations.

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.

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.

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.

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.

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.