Last data update: May 13, 2024. (Total: 46773 publications since 2009)
Records 1-21 (of 21 Records) |
Query Trace: Barry PM[original query] |
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Tuberculosis diagnostic delays and treatment outcomes among patients with COVID-19, California, USA, 2020
Han E , Nabity SA , Dasgupta-Tsinikas S , Guevara RE , Moore M , Kadakia A , Henry H , Cilnis M , Buhain S , Chitnis A , Chakrabarty M , Ky A , Nguyen Q , Low J , Jain S , Higashi J , Barry PM , Flood J . Emerg Infect Dis 2024 30 (1) 136-140 We assessed tuberculosis (TB) diagnostic delays among patients with TB and COVID-19 in California, USA. Among 58 persons, 43% experienced TB diagnostic delays, and a high proportion (83%) required hospitalization for TB. Even when viral respiratory pathogens circulate widely, timely TB diagnostic workup for at-risk persons remains critical for reducing TB-related illness. |
Sociodemographic Characteristics, Comorbidities, and Mortality Among Persons Diagnosed With Tuberculosis and COVID-19 in Close Succession in California, 2020.
Nabity SA , Han E , Lowenthal P , Henry H , Okoye N , Chakrabarty M , Chitnis AS , Kadakia A , Villarino E , Low J , Higashi J , Barry PM , Jain S , Flood J . JAMA Netw Open 2021 4 (12) e2136853 IMPORTANCE: Tuberculosis (TB) and COVID-19 are respiratory diseases that disproportionately occur among medically underserved populations; little is known about their epidemiologic intersection. OBJECTIVE: To characterize persons diagnosed with TB and COVID-19 in California. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional analysis of population-based public health surveillance data assessed the sociodemographic, clinical, and epidemiologic characteristics of California residents who were diagnosed with TB (including cases diagnosed and reported between September 3, 2019, and December 31, 2020) and COVID-19 (including confirmed cases based on positive results on polymerase chain reaction tests and probable cases based on positive results on antigen assays reported through February 2, 2021) in close succession compared with those who were diagnosed with TB before the COVID-19 pandemic (between January 1, 2017, and December 31, 2019) or diagnosed with COVID-19 alone (through February 2, 2021). This analysis included 3 402 713 California residents with COVID-19 alone, 6280 with TB before the pandemic, and 91 with confirmed or probable COVID-19 diagnosed within 120 days of a TB diagnosis (ie, TB/COVID-19). EXPOSURES: Sociodemographic characteristics, medical risk factors, factors associated with TB severity, and health equity index. MAIN OUTCOMES AND MEASURES: Frequency of reported successive TB and COVID-19 (TB/COVID-19) diagnoses within 120 days, frequency of deaths, and age-adjusted mortality rates. RESULTS: Among the 91 persons with TB/COVID-19, the median age was 58.0 years (range, 3.0-95.0 years; IQR, 41.0-73.0 years); 52 persons (57.1%) were male; 81 (89.0%) were born outside the US; and 28 (30.8%) were Asian or Pacific Islander, 4 (4.4%) were Black, 55 (60.4%) were Hispanic or Latino, 4 (4.4%) were White. The frequency of reported COVID-19 among those who received a TB diagnosis between September 3, 2019, and December 31, 2020, was 225 of 2210 persons (10.2%), which was similar to that of the general population (3 402 804 of 39 538 223 persons [8.6%]). Compared with persons with TB before the pandemic, those with TB/COVID-19 were more likely to be Hispanic or Latino (2285 of 6279 persons [36.4%; 95% CI, 35.2%-37.6%] vs 55 of 91 persons [60.4%; 95% CI, 49.6%-70.5%], respectively; P < .001), reside in low health equity census tracts (1984 of 6027 persons [32.9%; 95% CI, 31.7%-34.1%] vs 40 of 89 persons [44.9%; 95% CI, 34.4%-55.9%]; P = .003), live in the US longer before receiving a TB diagnosis (median, 19.7 years [IQR, 7.2-32.3 years] vs 23.1 years [IQR, 15.2-31.5 years]; P = .03), and have diabetes (1734 of 6280 persons [27.6%; 95% CI, 26.5%-28.7%] vs 42 of 91 persons [46.2%; 95% CI, 35.6%-56.9%]; P < .001). The frequency of deaths among those with TB/COVID-19 successively diagnosed within 30 days (8 of 34 persons [23.5%; 95% CI, 10.8%-41.2%]) was more than twice that of persons with TB before the pandemic (631 of 5545 persons [11.4%; 95% CI, 10.6%-12.2%]; P = .05) and 20 times that of persons with COVID-19 alone (42 171 of 3 402 713 persons [1.2%; 95% CI, 1.2%-1.3%]; P < .001). Persons with TB/COVID-19 who died were older (median, 81.0 years; IQR, 75.0-85.0 years) than those who survived (median, 54.0 years; IQR, 37.5-68.5 years; P < .001). The age-adjusted mortality rate remained higher among persons with TB/COVID-19 (74.2 deaths per 1000 persons; 95% CI, 26.2-122.1 deaths per 1000 persons) compared with either disease alone (TB before the pandemic: 56.3 deaths per 1000 persons [95% CI, 51.2-61.4 deaths per 1000 persons]; COVID-19 only: 17.1 deaths per 1000 persons [95% CI, 16.9-17.2 deaths per 1000 persons]). CONCLUSIONS AND RELEVANCE: In this cross-sectional analysis, TB/COVID-19 was disproportionately diagnosed among California residents who were Hispanic or Latino, had diabetes, or were living in low health equity census tracts. These results suggest that tuberculosis and COVID-19 occurring together may be associated with increases in mortality compared with either disease alone, especially among older adults. Addressing health inequities and integrating prevention efforts could avert the occurrence of concurrent COVID-19 and TB and potentially reduce deaths. |
State-level prevalence estimates of latent tuberculosis infection in the United States by medical risk factors, demographic characteristics and nativity.
Mirzazadeh A , Kahn JG , Haddad MB , Hill AN , Marks SM , Readhead A , Barry PM , Flood J , Mermin JH , Shete PB . PLoS One 2021 16 (4) e0249012 INTRODUCTION: Preventing tuberculosis (TB) disease requires treatment of latent TB infection (LTBI) as well as prevention of person-to-person transmission. We estimated the LTBI prevalence for the entire United States and for each state by medical risk factors, age, and race/ethnicity, both in the total population and stratified by nativity. METHODS: We created a mathematical model using all incident TB disease cases during 2013-2017 reported to the National Tuberculosis Surveillance System that were classified using genotype-based methods or imputation as not attributed to recent TB transmission. Using the annual average number of TB cases among US-born and non-US-born persons by medical risk factor, age group, and race/ethnicity, we applied population-specific reactivation rates (and corresponding 95% confidence intervals [CI]) to back-calculate the estimated prevalence of untreated LTBI in each population for the United States and for each of the 50 states and the District of Columbia in 2015. RESULTS: We estimated that 2.7% (CI: 2.6%-2.8%) of the U.S. population, or 8.6 (CI: 8.3-8.8) million people, were living with LTBI in 2015. Estimated LTBI prevalence among US-born persons was 1.0% (CI: 1.0%-1.1%) and among non-US-born persons was 13.9% (CI: 13.5%-14.3%). Among US-born persons, the highest LTBI prevalence was in persons aged ≥65 years (2.1%) and in persons of non-Hispanic Black race/ethnicity (3.1%). Among non-US-born persons, the highest LTBI prevalence was estimated in persons aged 45-64 years (16.3%) and persons of Asian and other racial/ethnic groups (19.1%). CONCLUSIONS: Our estimations of the prevalence of LTBI by medical risk factors and demographic characteristics for each state could facilitate planning for testing and treatment interventions to eliminate TB in the United States. Our back-calculation method feasibly estimates untreated LTBI prevalence and can be updated using future TB disease case counts at the state or national level. |
Impact and effectiveness of state-level tuberculosis interventions in California, Florida, New York and Texas: A model-based analysis
Shrestha S , Cherng S , Hill AN , Reynolds S , Flood J , Barry PM , Readhead A , Oxtoby M , Lauzardo M , Privett T , Marks SM , Dowdy DW . Am J Epidemiol 2019 188 (9) 1733-1741 The incidence of tuberculosis (TB) disease in the United States has stabilized, and additional interventions are needed to make progress toward TB elimination. But the impact of such interventions depends on local demography and heterogeneity in populations at risk. Using state-level individual-based TB transmission models, calibrated to California, Florida, New York, and Texas, we modeled two TB interventions: (i) Increased targeted testing and treatment (TTT) of high-risk populations, including people who are non-US-born, diabetic, HIV-positive, homeless, or incarcerated; and (ii) Enhanced TB contact investigation (ECI), including higher completion of preventive therapy. For each intervention, we projected reductions in active TB incidence over 10 years (2016-2026) and numbers needed to screen and treat to avert one case. TTT delivered to half of the non-US-born adult population could lower TB incidence by 19.8%-26.7% over ten years. TTT delivered to smaller populations with higher TB risk (e.g., HIV-positive, homeless) and ECI were generally more efficient, but had less overall impact on incidence. TTT targeted to smaller, highest-risk populations, and ECI can be highly efficient; however, major reductions in incidence will only be achieved by also targeting larger, moderate-risk populations. Ultimately, to eliminate TB in the US, a combination of these approaches is necessary. |
Outlook for tuberculosis elimination in California: An individual-based stochastic model
Goodell AJ , Shete PB , Vreman R , McCabe D , Porco TC , Barry PM , Flood J , Marks SM , Hill A , Cattamanchi A , Kahn JG . PLoS One 2019 14 (4) e0214532 RATIONALE: As part of the End TB Strategy, the World Health Organization calls for low-tuberculosis (TB) incidence settings to achieve pre-elimination (<10 cases per million) and elimination (<1 case per million) by 2035 and 2050, respectively. These targets require testing and treatment for latent tuberculosis infection (LTBI). OBJECTIVES: To estimate the ability and costs of testing and treatment for LTBI to reach pre-elimination and elimination targets in California. METHODS: We created an individual-based epidemic model of TB, calibrated to historical cases. We evaluated the effects of increased testing (QuantiFERON-TB Gold) and treatment (three months of isoniazid and rifapentine). We analyzed four test and treat targeting strategies: (1) individuals with medical risk factors (MRF), (2) non-USB, (3) both non-USB and MRF, and (4) all Californians. For each strategy, we estimated the effects of increasing test and treat by a factor of 2, 4, or 10 from the base case. We estimated the number of TB cases occurring and prevented, and net and incremental costs from 2017 to 2065 in 2015 U.S. dollars. Efficacy, costs, adverse events, and treatment dropout were estimated from published data. We estimated the cost per case averted and per quality-adjusted life year (QALY) gained. MEASUREMENTS AND MAIN RESULTS: In the base case, 106,000 TB cases are predicted to 2065. Pre-elimination was achieved by 2065 in three scenarios: a 10-fold increase in the non-USB and persons with MRF (by 2052), and 4- or 10-fold increase in all Californians (by 2058 and 2035, respectively). TB elimination was not achieved by any intervention scenario. The most aggressive strategy, 10-fold in all Californians, achieved a case rate of 8 (95% UI 4-16) per million by 2050. Of scenarios that reached pre-elimination, the incremental net cost was $20 billion (non-USB and MRF) to $48 billion. These had an incremental cost per QALY of $657,000 to $3.1 million. A more efficient but somewhat less effective single-lifetime test strategy reached as low as $80,000 per QALY. CONCLUSIONS: Substantial gains can be made in TB control in coming years by scaling-up current testing and treatment in non-USB and those with medical risks. |
Introduction and evaluation of multidrug-resistant tuberculosis supplemental surveillance in the United States
Belanger A , Morris SB , Brostrom R , Yost D , Goswami N , Oxtoby M , Moore M , Westenhouse J , Barry PM , Shah NS . J Clin Tuberc Other Mycobact Dis 2019 15 100090 The current tuberculosis (TB) case reporting system for the United States, the Report of Verified Case of TB (RVCT), has minimal capture of multidrug-resistant (MDR) TB treatment and adverse events. Data were abstracted in five states using the form for 13 MDR TB patients during 2012–2015. The Centers for Disease Control and Prevention Guidelines for Evaluating Public Health Surveillance Systems were used to evaluate attributes of the form. Unstructured interviews with pilot sites and stakeholders provided qualitative feedback. The form was acceptable, simple, stable, representative, and provided high-quality data but was not flexible or timely. For the 13 patients on whom data were collected, the median duration of treatment with an injectable medication was 216 days (IQR 203–252). Six (46%) patients reported a side effect requiring a medication change and eight (62%) had a side effect present at treatment completion. A standardized MDR TB supplemental surveillance form was well received by stakeholders whose feedback was critical to making modifications. The finalized form will be implemented nationally in 2020 and will provide MDR TB treatment and morbidity data in the United States to help ensure patients with MDR TB receive the most effective treatment regimens with the least toxic drugs. |
Evaluation of the impact of a sequencing assay for detection of drug resistance on the clinical management of tuberculosis.
Lowenthal P , Lin SG , Desmond E , Shah N , Flood J , Barry PM . Clin Infect Dis 2018 69 (4) 668-675 Background: In 2012, the California Department of Public Health began using pyrosequencing (PSQ) to detect mutations associated with resistance to isoniazid, rifampin, quinolones and injectable drugs in Mycobacterium tuberculosis complex. We evaluated the impact of the PSQ assay on the clinical management of tuberculosis (TB) in California. Methods: TB surveillance and laboratory data for specimens submitted 8/1/2012-12/31/2016 were analyzed to determine time to effective treatment initiation. A survey of clinicians was used to assess how PSQ results influenced clinical decision-making. Results: Of 1,957 specimens tested with PSQ, 52% were sediments and 46% were culture isolates, submitted 8 and 35 days (median) after collection, respectively. Among 36 patients with multidrug-resistant TB (MDR-TB) who had a sediment specimen submitted for PSQ, median time from specimen collection to MDR-TB treatment initiation was 12 days vs 51 days when PSQ was not used. Of 303 TB patients with a completed survey, 126 (42%) clinicians reported PSQ as a reason for treatment change. Twenty-one patients either had an MDR-TB risk factor and a smear positive sputum specimen, but had PSQ performed on a culture isolate (9 of 36; 25%); or, didn't have PSQ used for MDR-TB diagnosis (12 of 38; 32%) and thus, had an opportunity for earlier MDR-TB diagnosis with PSQ on sediment. Conclusions: Patients with MDR-TB initiated effective treatment five weeks earlier when PSQ was used compared to those without PSQ. Survey data suggest clinicians use PSQ to devise effective TB drug regimens. To maximize the benefit of PSQ, earlier submission of specimens should be prioritized. |
Treatment correlates of successful outcomes in pulmonary multidrug-resistant tuberculosis: an individual patient data meta-analysis
Ahmad N , Ahuja SD , Akkerman OW , Alffenaar JC , Anderson LF , Baghaei P , Bang D , Barry PM , Bastos ML , Behera D , Benedetti A , Bisson GP , Boeree MJ , Bonnet M , Brode SK , Brust JCM , Cai Y , Caumes E , Cegielski JP , Centis R , Chan PC , Chan ED , Chang KC , Charles M , Cirule A , Dalcolmo MP , D'Ambrosio L , de Vries G , Dheda K , Esmail A , Flood J , Fox GJ , Frechet-Jachym M , Fregona G , Gayoso R , Gegia M , Gler MT , Gu S , Guglielmetti L , Holtz TH , Hughes J , Isaakidis P , Jarlsberg L , Kempker RR , Keshavjee S , Khan FA , Kipiani M , Koenig SP , Koh WJ , Kritski A , Kuksa L , Kvasnovsky CL , Kwak N , Lan Z , Lange C , Laniado-Laborin R , Lee M , Leimane V , Leung CC , Leung EC , Li PZ , Lowenthal P , Maciel EL , Marks SM , Mase S , Mbuagbaw L , Migliori GB , Milanov V , Miller AC , Mitnick CD , Modongo C , Mohr E , Monedero I , Nahid P , Ndjeka N , O'Donnell MR , Padayatchi N , Palmero D , Pape JW , Podewils LJ , Reynolds I , Riekstina V , Robert J , Rodriguez M , Seaworth B , Seung KJ , Schnippel K , Shim TS , Singla R , Smith SE , Sotgiu G , Sukhbaatar G , Tabarsi P , Tiberi S , Trajman A , Trieu L , Udwadia ZF , van der Werf TS , Veziris N , Viiklepp P , Vilbrun SC , Walsh K , Westenhouse J , Yew WW , Yim JJ , Zetola NM , Zignol M , Menzies D . Lancet 2018 392 (10150) 821-834 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 I(2) 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. |
The California Multidrug-Resistant Tuberculosis Consult Service: a partnership of state and local programs
Shah NS , Westenhouse J , Lowenthal P , Schecter G , True L , Mase S , Barry PM , Flood J . Public Health Action 2018 8 (1) 7-13 Background: The US Centers for Disease Control and Prevention recommend expert consultation for multi-drug-resistant tuberculosis (MDR-TB) cases. In 2002, the California MDR-TB Service was created to provide expert MDR-TB consultations. We describe the characteristics, treatment outcomes and management of patients referred to the Service. Methods: Surveillance data were used for descriptive analysis of cases, with consultation during July 2002-December 2012. Clinical consultation data and modified World Health Organization indicators were used to assess the care and management of cases, with consultation from January 2009 to December 2012. Results: Of 339 MDR-TB patients, 140 received a consultation. The proportion of patients receiving a consultation increased from 12% in 2002 to 63% in 2012. There were 24 pre-extensively drug-resistant TB and 5 patients with extensively drug-resistant TB. The majority (n = 123, 88%) completed treatment, 5 (4%) died, 7 (5%) moved before treatment completion, 4 (3%) stopped treatment due to an adverse event and 1 (1%) had an unknown outcome. Indicator data showed that 86% underwent rapid molecular drug susceptibility testing, 98% received at least four drugs to which they had known or presumed susceptibility, and 93% culture converted within 6 months. Conclusions: Consultations with the MDR-TB Service increased over time. Results highlight successful treatment and indicator outcomes. |
Tuberculosis mortality in the United States: Epidemiology and prevention opportunities
Beavers SF , Pascopella L , Davidow AL , Mangan JM , Hirsch-Moverman YR , Golub JE , Blumberg HM , Webb RM , Royce RA , Buskin SE , Leonard MK , Weinfurter PC , Belknap RW , Hughes SE , Warkentin JV , Welbel SF , Miller TL , Kundipati SR , Lauzardo M , Barry PM , Katz DJ , Garrett DO , Graviss EA , Flood JM . Ann Am Thorac Soc 2018 15 (6) 683-692 RATIONALE: More information on risk factors for death from tuberculosis in the United States could help reduce the tuberculosis mortality rate, which has remained steady for over a decade. Objective(s) To identify risk factors for tuberculosis-related death in adults. METHODS: We performed a retrospective study of 1,304 adults with tuberculosis who died before treatment completion and 1,039 frequency-matched controls who completed tuberculosis treatment in 2005-2006 in thirteen states reporting 65% of U.S. tuberculosis cases. We used in-depth record abstractions and a standard algorithm to classify deaths in persons with tuberculosis as tuberculosis-related or not. We then compared these classifications to causes of death as coded in death certificates. We used multivariable logistic regression to calculate adjusted odds ratios (aOR) for predictors of tuberculosis-related death among adults compared with those who completed tuberculosis treatment. RESULTS: Of 1,304 adult deaths, 942 (72%) were tuberculosis-related, 272 (21%) were not, and 90 (7%) couldn't be classified. Of 847 tuberculosis-related deaths with death certificates available, 378 (45%) did not list tuberculosis as a cause of death. Adjusting for known risks, we identified new risks for tuberculosis-related death during treatment: absence of pyrazinamide in the initial regimen (aOR=3.4, 95% CI=1.9-6.0); immunosuppressive medications (aOR=2.5, 95% CI=1.1-5.6); incomplete TB diagnostic evaluation (aOR=2.2, 95% CI=1.5-3.3), and an alternative non-TB diagnosis prior to TB diagnosis (aOR=1.6, 95% CI=1.2-2.2). Conclusions Most persons who died with tuberculosis had a tuberculosis-related death. Intensive record review revealed tuberculosis as a cause of death more often than did death certificate diagnoses. New tools, such as a TB mortality risk score based on our study findings, may identify TB patients for in-hospital interventions to prevent death. |
Increased tuberculosis risk among immigrants arriving in California with abnormal domestic chest radiographs
Wong J , Lowenthal P , Flood J , Watt J , Barry PM . Int J Tuberc Lung Dis 2018 22 (1) 73-79 SETTING: Tuberculosis (TB) cases in California, USA, occur predominantly among foreign-born persons, many of whom have abnormal chest radiographs (CXRs) on overseas medical examination. These persons are recommended for follow-up TB evaluation upon arrival in the United States. OBJECTIVE: To estimate the increased TB risk associated with abnormal vs. normal domestic CXRs among individuals arriving with abnormal overseas CXRs. DESIGN: Cox regression analyses of 35 633 foreign-born persons aged >/=15 years who arrived in California during 1999-2012 with abnormal overseas CXRs and were free of imported active TB. Domestic CXRs were conducted during post-arrival evaluation. Subsequent cases through 2014 were identified from California's TB registry. RESULTS: A total of 121 (0.3%) arrivers developed TB disease. Progression rates were respectively 63.6 (95%CI 50.8-76.4) and 25.4 (95% CI 15.7-35.2) cases/100 000 person-years among persons with abnormal and normal domestic CXRs. Relative to arrivers with normal domestic CXRs, those with abnormal domestic CXRs had an elevated disease risk during the first 4 years after immigration; this increased risk was greatest during the first year (hazard ratio 2.9, 95%CI 1.8-4.8). CONCLUSION: Among arrivers with abnormal overseas CXRs, those with abnormal CXRs upon domestic evaluation have an elevated disease risk and represent an important target group for preventive treatment. |
Solid Organ Transplant-Transmitted Tuberculosis Linked to a Community Outbreak - California, 2015.
Kay A , Barry PM , Annambhotla P , Greene C , Cilnis M , Chin-Hong P , Arger N , McNitt L , Neidlinger N , Shah N , Basavaraju SV , Kuehnert M , Shaw T . MMWR Morb Mortal Wkly Rep 2017 66 (30) 801-805 In the spring of 2015, a local health department (LHD) in county A notified the California Department of Public Health (CDPH) about three adults with close ties to one another and a congregate community site who had received diagnoses of tuberculosis (TB) disease within a 3-month period. Subsequent review revealed matching TB genotypes indicating that the cases were likely part of a chain of TB transmission. Only three TB cases in California in the preceding 2 years shared this same genotype. One of those three previous cases occurred in a lung-transplant recipient who had no identified epidemiologic links to the outbreak. CDPH, multiple LHDs, and CDC conducted an investigation and determined that the lung-transplant donor (patient 1) was epidemiologically linked to the three outbreak cases and had a tuberculin skin test (TST) conversion detected in 2012 upon reentry at a local jail. Three other solid organ recipients from this donor were identified; none had developed TB disease. This investigation suggests that review of organ donors' medical records from high-risk environments, such as jails, might reveal additional information about TB risk. The evaluation of TB in organ recipients could include genotyping analysis (1) and coordination among local, state, and national partners to evaluate the potential for donor-derived TB. |
Tuberculosis trends in California correctional facilities, 1993-2013
McDaniel CJ , Chitnis AS , Barry PM , Shah N . Int J Tuberc Lung Dis 2017 21 (8) 922-929 BACKGROUND: Incarcerated persons are disproportionately diagnosed with tuberculosis (TB). California has the second highest inmate population in the United States, but reports the highest number of cases. OBJECTIVE: To describe the TB epidemiology among incarcerated patients in California. METHODS : Trends in incidence were assessed using Poisson regression, and trends in percentage were assessed using weighted linear regression. Demographic and clinical characteristics were compared using v2 or Mann-Whitney U tests. RESULTS: During 1993-2013, of the 64 090 TB cases reported, 2323 (4%) were correctional facility residents. Incidence in correctional facilities decreased until 2006 (annual per cent change [APC] -12.3%, 95%CI -14.4 to -10.1), but has since stabilized (APC 4.4%, 95%CI -2.1 to 11.4). Compared with state prisoners, federal prisoners were more likely to be male (98%, P<0.03), persons arriving in the United States within 5 years of diagnosis (62%, P< 0.001), and born in Mexico (88%, P=0.02), whereas local jail inmates were more likely to have a history of substance use (75%, P<0.001) and homelessness (35%, P< 0.001). CONCLUSIONS: TB incidence in correctional facilities had steadily declined over the last two decades, but has recently leveled out. To promote further reduction in incidence among diverse incarcerated populations, health departments and correctional facilities should strengthen collaboration by conducting TB risk-based assessments. |
Benefit of the shorter MDR TB treatment regimen in California and modified eligibility criteria
Barry PM , Lowenthal P , True L , Henry L , Schack G , Wendorf K , Flood J , Shah N . Am J Respir Crit Care Med 2017 196 (11) 1488-1489 As consultants for multidrug-resistant (MDR) tuberculosis (TB) cases in California, we read with interest the correspondence from Varaine and colleagues (1) and Lange and colleagues (2) regarding the new World Health Organization–recommended shorter treatment for MDR TB (3). As Varaine and colleagues noted, the importance for short-course treatment eligibility of resistance to drugs other than injectables and fluoroquinolones remains unclear in the recommendations (1). This has implications for both programs that do and those that do not routinely perform susceptibility testing to all second-line drugs. One specific question is whether or not patients who have Mycobacterium tuberculosis organisms that are resistant to ethionamide but have only low-level isoniazid resistance are eligible. Considering these patients eligible makes sense, given the drugs included in the shorter regimen. High-dose isoniazid is likely to be active against organisms with low-level isoniazid resistance, commonly associated with a mutation in the inhA gene that also confers resistance to ethionamide (4–6). The efficacy of high-dose isoniazid for organisms with low-level isoniazid resistance is under study (ClinicalTrials.gov identifier: NCT01936831). Ethionamide is more likely to be active against M. tuberculosis organisms with high-level resistance to isoniazid, associated with a mutation in katG, and that are less commonly resistant to ethionamide (5). The shorter regimen includes both ethionamide and high-dose isoniazid and therefore is likely to be effective against both of these common MDR TB resistance patterns. Lange and colleagues reported that fewer than 8% of patients in Europe with MDR TB would be eligible to be treated with the shorter regimen but did not include information about how many patients’ organisms had low-level isoniazid resistance or an inhA mutation (2). |
Epidemiology of pediatric multidrug-resistant tuberculosis in the United States, 1993-2014
Smith SE , Pratt R , Trieu L , Barry PM , Thai DT , Ahuja SD , Shah S . Clin Infect Dis 2017 65 (9) 1437-1443 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 (<15 years) TB cases reported to the US National TB Surveillance System (NTSS) during 1993-2014. MDR TB was defined as culture-confirmed TB disease with resistance to at least isoniazid and rifampicin. To ascertain potential under-estimation of pediatric MDR TB, we surveyed high burden states for clinically-diagnosed cases treated for MDR TB. Results: Of 20,789 pediatric TB cases, 5,162 (24.8%) had bacteriologically-confirmed TB. Among 4,862 (94.2%) 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 (IQR 1-12), one-third were Hispanic (n=28, 34%), and two-thirds (n=55, 67%) were born in the US. Most cases had additional resistance to ≥1 other first-line drug (n=66; 80.5%) 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 four high TB burden states/jurisdictions surveyed, there was 42-55% under-estimation 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 US using strictly bacteriologic criteria. Better estimates of pediatric MDR TB burden in the US are needed and should include clinical diagnoses based on epidemiologic criteria. |
Clinical Impact on Tuberculosis Treatment Outcomes of Discordance Between Molecular and Growth-Based Assays for Rifampin Resistance, California 2003-2013.
Shah NS , Grace Lin SY , Barry PM , Cheng YN , Schecter G , Desmond E . Open Forum Infect Dis 2016 3 (3) ofw150 Background. Data from international settings suggest that isolates of Mycobacterium tuberculosis with rpoB mutations testing phenotypically susceptible to rifampin (RIF) may have clinical significance. We analyzed treatment outcomes of California patients with discordant molecular-phenotypic RIF results. Methods. We included tuberculosis (TB) patients, during 2003-2013, whose specimens tested RIF susceptible phenotypically but had a rpoB mutation determined by pyrosequencing. Demographic data were abstracted from the California TB registry. Phenotypic drug-susceptibility testing, medical history, treatment, and outcomes were abstracted from medical records. Results. Of 3330 isolates tested, 413 specimens had a rpoB mutation (12.4%). Of these, 16 (3.9%) had molecular-phenotypic discordant RIF results. Seven mutations were identified: 511Pro, 516Phe, 526Asn, 526Ser (AGC and TCC), 526Cys, and 533Pro. Fourteen (88%) had isoniazid (INH) resistance, 6 of whom were also phenotypically resistant to ethambutol (EMB) and/or pyrazinamide (PZA). Five patients (25%), 1 with 511Pro and 4 with 526Asn, relapsed or failed treatment. The initial regimen for 3 patients was RIF, PZA, and EMB; 1 patient received RIF, PZA, EMB, and a fluoroquinolone (FQN); and 1 patient received RIF, EMB, FQN, and some second-line medications. Upon retreatment with an expanded regimen, 3 (75%) patients completed treatment, 1 patient moved before treatment completion, and 1 patient continues on treatment. The remaining 11 patients had a successful outcome with 9 having received a FQN and/or a rifamycin. Conclusions. Rifampin molecular-phenotypic discordance was rare, and most isolates had INH resistance. Patients who did not receive an expanded regimen had poor outcomes. These mutations may have clinical importance, and expanded treatment regimens should be considered. |
Executive Summary: Official American Thoracic Society/Centers for Disease Control and Prevention/Infectious Diseases Society of America Clinical Practice Guidelines: Treatment of drug-susceptible tuberculosis
Nahid P , Dorman SE , Alipanah N , Barry PM , Brozek JL , Cattamanchi A , Chaisson LH , Chaisson RE , Daley CL , Grzemska M , Higashi JM , Ho CS , Hopewell PC , Keshavjee SA , Lienhardt C , Menzies R , Merrifield C , Narita M , O'Brien R , Peloquin CA , Raftery A , Saukkonen J , Schaaf HS , Sotgiu G , Starke JR , Migliori GB , Vernon A . Clin Infect Dis 2016 63 (7) 853-67 The American Thoracic Society, Centers for Disease Control and Prevention, and Infectious Diseases Society of America jointly sponsored the development of this guideline for the treatment of drug-susceptible tuberculosis, which is also endorsed by the European Respiratory Society and the US National Tuberculosis Controllers Association. Representatives from the American Academy of Pediatrics, the Canadian Thoracic Society, the International Union Against Tuberculosis and Lung Disease, and the World Health Organization also participated in the development of the guideline. This guideline provides recommendations on the clinical and public health management of tuberculosis in children and adults in settings in which mycobacterial cultures, molecular and phenotypic drug susceptibility tests, and radiographic studies, among other diagnostic tools, are available on a routine basis. For all recommendations, literature reviews were performed, followed by discussion by an expert committee according to the Grading of Recommendations, Assessment, Development and Evaluation methodology. Given the public health implications of prompt diagnosis and effective management of tuberculosis, empiric multidrug treatment is initiated in almost all situations in which active tuberculosis is suspected. Additional characteristics such as presence of comorbidities, severity of disease, and response to treatment influence management decisions. Specific recommendations on the use of case management strategies (including directly observed therapy), regimen and dosing selection in adults and children (daily vs intermittent), treatment of tuberculosis in the presence of HIV infection (duration of tuberculosis treatment and timing of initiation of antiretroviral therapy), as well as treatment of extrapulmonary disease (central nervous system, pericardial among other sites) are provided. The development of more potent and better-tolerated drug regimens, optimization of drug exposure for the component drugs, optimal management of tuberculosis in special populations, identification of accurate biomarkers of treatment effect, and the assessment of new strategies for implementing regimens in the field remain key priority areas for research. See the full-text online version of the document for detailed discussion of the management of tuberculosis and recommendations for practice. |
Official American Thoracic Society/Centers for Disease Control and Prevention/Infectious Diseases Society of America Clinical Practice Guidelines: Treatment of drug-susceptible tuberculosis
Nahid P , Dorman SE , Alipanah N , Barry PM , Brozek JL , Cattamanchi A , Chaisson LH , Chaisson RE , Daley CL , Grzemska M , Higashi JM , Ho CS , Hopewell PC , Keshavjee SA , Lienhardt C , Menzies R , Merrifield C , Narita M , O'Brien R , Peloquin CA , Raftery A , Saukkonen J , Schaaf HS , Sotgiu G , Starke JR , Migliori GB , Vernon A . Clin Infect Dis 2016 63 (7) e147-e195 The American Thoracic Society, Centers for Disease Control and Prevention, and Infectious Diseases Society of America jointly sponsored the development of this guideline for the treatment of drug-susceptible tuberculosis, which is also endorsed by the European Respiratory Society and the US National Tuberculosis Controllers Association. Representatives from the American Academy of Pediatrics, the Canadian Thoracic Society, the International Union Against Tuberculosis and Lung Disease, and the World Health Organization also participated in the development of the guideline. This guideline provides recommendations on the clinical and public health management of tuberculosis in children and adults in settings in which mycobacterial cultures, molecular and phenotypic drug susceptibility tests, and radiographic studies, among other diagnostic tools, are available on a routine basis. For all recommendations, literature reviews were performed, followed by discussion by an expert committee according to the Grading of Recommendations, Assessment, Development and Evaluation methodology. Given the public health implications of prompt diagnosis and effective management of tuberculosis, empiric multidrug treatment is initiated in almost all situations in which active tuberculosis is suspected. Additional characteristics such as presence of comorbidities, severity of disease, and response to treatment influence management decisions. Specific recommendations on the use of case management strategies (including directly observed therapy), regimen and dosing selection in adults and children (daily vs intermittent), treatment of tuberculosis in the presence of HIV infection (duration of tuberculosis treatment and timing of initiation of antiretroviral therapy), as well as treatment of extrapulmonary disease (central nervous system, pericardial among other sites) are provided. The development of more potent and better-tolerated drug regimens, optimization of drug exposure for the component drugs, optimal management of tuberculosis in special populations, identification of accurate biomarkers of treatment effect, and the assessment of new strategies for implementing regimens in the field remain key priority areas for research. See the full-text online version of the document for detailed discussion of the management of tuberculosis and recommendations for practice. |
Genomic epidemiology of multidrug-resistant Mycobacterium tuberculosis during transcontinental spread.
Coscolla M , Barry PM , Oeltmann JE , Koshinsky H , Shaw T , Cilnis M , Posey J , Rose J , Weber T , Fofanov VY , Gagneux S , Kato-Maeda M , Metcalfe JZ . J Infect Dis 2015 212 (2) 302-10 The transcontinental spread of multidrug-resistant tuberculosis (MDR-TB) is poorly characterized in molecular epidemiologic studies. We utilized genomic sequencing to understand the establishment and dispersion of MDR-Mycobacterium tuberculosis within an immigrant group to the United States. We used a genomic epidemiology approach to study a genotypically-matched (spoligotype, IS6110, MIRU-VNTR) Lineage 2/Beijing MDR strain implicated in an outbreak among refugees in Thailand and consecutive cases within California, USA. All 46 MDR genomes from both Thailand and California were highly related with a median difference of 10 single nucleotide polymorphisms (SNPs). The WTK strain is a new sequence type distinguished from all known Beijing strains by 55 SNPs and a genomic deletion (Rv1267c) associated with increased fitness. Sequence data revealed a highly prevalent MDR strain that included several closely related but distinct allelic variants within Thailand, rather than a single outbreak. In California, sequencing data supported multiple independent introductions of WTK with subsequent transmission and reactivation within the state, and a potential "super spreader" with a prolonged infectious period. Twenty-seven drug resistance-conferring mutations and four putative compensatory mutations were found within WTK strains. Genomic sequencing has substantial epidemiologic value in both low- and high-burden settings in understanding transmission chains of highly prevalent MDR strains. |
Multistate outbreak of MDR TB identified by genotype cluster investigation.
Barry PM , Gardner TJ , Funk E , Oren E , Field K , Shaw T , Langer AJ . Emerg Infect Dis 2012 18 (1) 113-6 In 2008, diagnosis and investigation of 2 multidrug-resistant tuberculosis cases with matching genotypes led to identification of an outbreak among foreign-born persons who performed short-term seafood production work in Alaska during 2006. Tuberculosis control programs should consider the possibility of domestic transmission even among foreign-born patients. |
Results of a program to test women for rectal chlamydia and gonorrhea
Barry PM , Kent CK , Philip SS , Klausner JD . Obstet Gynecol 2010 115 (4) 753-9 OBJECTIVE: To analyze whether rectal testing among women increased chlamydia and gonorrhea case-finding and whether reported receptive anal intercourse was a risk factor for rectal infection. METHODS: From March 2007 to August 2008, women receiving pelvic examinations at the San Francisco sexually transmitted disease clinic were tested for rectal gonorrhea and chlamydia by using a transcription-mediated amplification assay. Results of testing and clinical and demographic data were analyzed using a cross-sectional study design. RESULTS: Of 1,308 women with both rectal and vaginal tests, test results were positive for 79 patients (6.0%) for rectal chlamydia or gonorrhea and 88 patients (6.7%) for genital chlamydia or gonorrhea. Test results were positive for 13 patients (1.0%) at the rectum only, increasing detection from 88 to 101 patients (14.8%; 95% confidence interval 8.1-23.9). No correlation existed between reported anal sex and rectal chlamydia (P=.74); however, 50% of women with rectal gonorrhea reported anal sex compared with 21% of women without rectal gonorrhea (P=.002). CONCLUSION: Sexually transmitted disease clinics might improve chlamydia and gonorrhea case-finding through rectal testing of women, but more study is needed to determine the effects of finding and treating such infections. Reporting anal intercourse did not predict rectal chlamydial infection among women tested at both the rectum and the vagina. LEVEL OF EVIDENCE: II. |
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