Last data update: May 06, 2024. (Total: 46732 publications since 2009)
Records 1-19 (of 19 Records) |
Query Trace: Ho CS[original query] |
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Long-term follow-up of persons diagnosed with multidrug-resistant TB in Chennai, India, 2013-2020
Surie D , Sathyanarayanan MK , Lavanya J , Smith JP , Shanmugam SK , Tamilzhalagan S , Selvaraj A , Ramesh G , Tripathy S , Khaparde SD , Ho CS , Hall-Eidson PJ , Ranganathan UDK , Selvaraju S , Moonan PK . Int J Tuberc Lung Dis 2024 28 (1) 54-56 India has the largest number of multidrug-resistant TB | (MDR-TB) cases, defined as Mycobacterium tuberculosis | resistant to at least isoniazid (INH) and rifampicin (RIF).1 | However, less than half of all persons with MDR-TB in | India successfully complete treatment.1 Although initial | end-of-treatment outcomes offer a standardised time point | to assess the effect of treatment, these tend to | underestimate the overall burden of unfavourable longterm outcomes among persons treated for TB.2,3 The longterm outcomes of persons diagnosed with MDR-TB in | India, including the proportion with recurrent TB disease | or mortality, are unknown. This analysis was conducted | under programmatic conditions in a high-burden setting, | with no regular check-ups after treatment. The results can | be used to show the burden of recurrent illness and death | following treatment, and can be used as a benchmark to | measure improvement. |
Examining test cutoffs to optimize diagnosis of latent tuberculosis infection in non-US-born people
Zavala S , Winglee K , Ho CS , Pettit AC , Ahmed A , Katz DJ , Belknap RW , Stout JE . Ann Am Thorac Soc 2023 20 (9) 1258-1266 RATIONALE: Detection of latent tuberculosis infection (LTBI) in persons born in high tuberculosis (TB) incidence countries living in low TB incidence countries is key to tuberculosis elimination in low-incidence countries. Optimizing LTBI tests is critical to targeting treatment. OBJECTIVES: To compare the sensitivity/specificity of tuberculin skin test (TST) and two interferon-gamma release assays (IGRA) at different cutoffs, and of a single test versus dual testing. METHODS: We examined a subset (N=14,167) of a prospective cohort of people in the United States tested for LTBI. We included non-US-born, HIV-seronegative people ages 5 years and older with valid TST, QuantiFERON-TB Gold-in-Tube(QFT), and T-SPOT.TB(TSPOT) results. The sensitivity/specificity of different test cutoffs and test combinations, obtained from a Bayesian latent class model, were used to construct receiver operating characteristic (ROC) curves and assess area under the curve (AUC) for each test. The sensitivity/specificity of dual testing were calculated. RESULTS: The AUC of the TST ROC curve was 0.81(95% Credible Interval(CrI) 0.78-0.86), with sensitivity/specificity at cutoffs of 5, 10, and 15mm of 86.5%/61.6%, 81.7%/71.3, and 55.6%/88.0%, respectively. The AUC of the QFT ROC curve was 0.89(95%CrI 0.86-0.93), with sensitivity/specificity at cutoffs of 0.35, 0.7, and 1.0IU/mL of 77.7%/98.3%, 66.9%/99.1%, and 61.5/99.4%. The AUC of the TSPOT ROC curve was 0.92(95%CrI 0.88-0.96) with sensitivity/specificity for 5, 6, 7, and 8 spots of 79.2%/96.7%, 76.8%/97.7%, 74.0%/98.6%, and 71.8%/99.5%. Sensitivity/specificity of TST-QFT, TST-TSPOT and QFT-TSPOT at standard cutoffs were 73.1%/99.4%, 64.8%/99.8%, and 65.3%/100%. CONCLUSION: IGRAs have a better predictive ability than TST in people at high risk of LTBI. |
Retaining patients with drug-resistant tuberculosis on treatment during the COVID-19 pandemic - Dharavi, Mumbai, India, 2020-2022
Gomare MD , Bhide S , Deshmukh R , Kaipilyawar S , Puri V , Moonan PK , Khetade DK , Nyendak M , Yeldandi V , Smith JP , Tobias JL , Date A , Joshi R , Kumar R , Ho CS . MMWR Morb Mortal Wkly Rep 2023 72 (12) 304-308 Mumbai, India's second largest city, has one of the highest prevalences of drug-resistant tuberculosis* (DRTB) in the world. Treatment for DRTB takes longer and is more complicated than treatment for drug-susceptible tuberculosis (TB). Approximately 300 persons receive a new DRTB diagnosis each year in Mumbai's Dharavi slum(†); historically, fewer than one half of these patients complete DRTB treatment. As nationwide restrictions to mitigate the COVID-19 pandemic were implemented, a program to facilitate uninterrupted DRTB care for patients receiving treatment was also implemented. A comprehensive tool and risk assessment provided support to DRTB patients and linked those who relocated outside of Dharavi during the pandemic to DRTB care at their destination. During May 2020-September 2022, a total of 973 persons received DRTB treatment in Dharavi, including 255 (26%) who relocated during treatment. Overall, 25 (3%) DRTB patients were lost to follow-up, a rate substantially lower than the rate before the pandemic (18%). Proactive planning and implementation of simple tools retained patients on treatment during periods of travel restrictions and relocations, improving programmatic outcomes. This approach might aid public health programs serving migrant populations or patients receiving treatment for DRTB during public health emergencies. |
Comparison of three tests for latent tuberculosis infection in high-risk people in the USA: an observational cohort study
Ho CS , Feng PI , Narita M , Stout JE , Chen M , Pascopella L , Garfein R , Reves R , Katz DJ . Lancet Infect Dis 2021 22 (1) 85-96 BACKGROUND: Treatment of latent tuberculosis infection is an important strategy to prevent tuberculosis disease. In the USA, three tests are used to identify latent tuberculosis infection: the tuberculin skin test (TST) and two IFN-γ release assays (T-SPOT.TB and QuantiFERON). To our knowledge, few large studies have compared all three tests among people at high risk of latent tuberculosis infection or progression to tuberculosis disease. We aimed to assess test agreement between IFN-γ release assays and TST to provide guidance on their use in important risk groups. METHODS: In this observational cohort study, we enrolled participants at high risk of latent tuberculosis infection or progression to tuberculosis disease at ten US sites with 18 affiliated clinics, including close contacts of infectious tuberculosis cases, people born in countries whose populations in the USA have high (≥100 cases per 100 000 people) or moderate (10-99 cases per 100 000 people) tuberculosis incidence, and people with HIV. Participants were interviewed about demographics and medical risk factors, and all three tests were administered to each participant. The primary endpoints for this study were the proportions of positive test results by test type stratified by risk group and test concordance by risk group for participants with valid results for all three test types. The study is registered at ClinicalTrials.gov, NCT01622140. FINDINGS: Between July 12, 2012, and May 5, 2017, 26 292 people were approached and 22 131 (84·2%) were enrolled in the study. Data from 21 846 (98·7%) participants were available for analysis, including 3790 (17·3%) born in the USA and 18 023 (82·5%) born outside the USA. Among non-US-born participants overall, the RR comparing the proportions of TST-positive results (7476 [43·2%] of 17 306 participants) to QuantiFERON-positive results (4732 [26·5%] of 17 882 participants) was 1·6 (95% CI 1·6-1·7). The risk ratio (RR) for the comparison with the proportion of T-SPOT.TB-positive results (3693 [21·6%] of 17 118 participants) was 2·0 (95% CI 1·9-2·1). US-born participants had less variation in the proportions of positive results across all tests. The RRs for the proportion of TST-positive results (391 [10·9%] of 3575 participants) compared with the proportion of QuantiFERON-positive results (445 [12·0%] of 3693 participants) and T-SPOT.TB-positive results (295 [8·1%] of 3638 participants) were 0·9 (95% CI 0·8-1·0) and 1·3 (1·2-1·6), respectively. 20 149 (91·0%) of 21 846 participants had results for all three tests, including 16 712 (76%) non-US-born participants. Discordance between TST and IFN-γ release assay results varied by age among non-US-born participants and was greatest among the 848 non-US-born children younger than 5 years. 204 (87·2%) of 234 non-US-born children younger than 5 years with at least one positive test were TST-positive and IFN-γ release assay-negative. The proportion of non-US-born participants who were TST-negative but IFN-γ release assay-positive ranged from one (0·5%) of 199 children younger than 2 years to 86 (14·5%) of 594 participants aged 65 years and older (p(trend)<0·0001). Test agreement was higher between the two IFN-γ release assays than between TST and either IFN-γ release assay, regardless of birthplace. κ agreement was particularly low between TST and IFN-γ release assays in non-US-born children younger than 5 years. INTERPRETATION: Our findings support the preferential use of IFN-γ release assays for the diagnosis of latent tuberculosis in high-risk populations, especially in very young and older people born outside the USA. FUNDING: US Centers for Disease Control and Prevention. |
Impact of T-Cell Xtend on T-SPOT.TB Assay in High-Risk Individuals after Delayed Blood Sample Processing
Feng PJ , Wu Y , Ho CS , Chinna L , Whelen AC , Largen A , Brostrom R , Reves R , Belknap R , Cattamanchi A , Banaei N . J Clin Microbiol 2021 59 (5) T-SPOT®.TB (T-SPOT) is an interferon-gamma release assay (IGRA) used to detect infection with Mycobacterium tuberculosis based on the number of spot-forming T-cells; however, delays in sample processing have been shown to reduce the number of these spots that are detected following laboratory processing. Adding T-Cell Xtend (XT) into blood samples before processing reportedly extends the amount of time allowed between blood collection and processing up to 32 hours. In this study, paired blood samples from 306 adolescents and adults at high risk for latent tuberculosis (TB) infection (LTBI) or progression to TB disease were divided into three groups: 1) early processing (∼4.5 hours after collection) with and without XT, 2) delayed processing (∼24 hours after collection) with and without XT, and 3) early processing without XT and delayed processing with XT. The participants' paired samples were processed at a local laboratory and agreement of qualitative and quantitative results were assessed. The addition of XT did not consistently increase or decrease the number of spots. In groups 1, 2, and 3, samples processed with XT had 13% (10/77), 28.0% (30/107) and 24.6% (30/122), respectively, more spots while 33.8% (26/77), 26.2% (28/107), and 38.5% (47/122) had less spots compared with samples processed without XT. The findings suggest that XT does not reliably mitigate the loss of spot-forming T-cells in samples with processing delay. |
Prevalence of latent tuberculosis infection among non-U.S.-born persons by country of birth - United States, 2012-2017
Collins JM , Stout JE , Ayers T , Hill AN , Katz DJ , Ho CS , Blumberg HM , Winglee K . Clin Infect Dis 2020 73 (9) e3468-e3475 BACKGROUND: Most tuberculosis (TB) disease in the U.S. is attributed to reactivation of remotely acquired latent TB infection (LTBI) in non-U.S.-born persons who were likely infected with Mycobacterium tuberculosis in their countries of birth. Information on LTBI prevalence by country of birth could help guide local providers and health departments to scale up the LTBI screening and preventive treatment needed to advance progress towards TB elimination. METHODS: 13 805 non-U.S.-born persons at high risk of TB infection or progression to TB disease were screened for LTBI at 16 clinical sites located across the United States with a tuberculin skin test, QuantiFERON ® Gold In-Tube test, and T-SPOT ®.TB test. Bayesian latent class analysis was applied to test results to estimate LTBI prevalence and associated credible intervals (CRI) for each country or world region of birth. RESULTS: Among the study population, the estimated LTBI prevalence was 31% (95% CRI 26% - 35%). Country-of-birth-level LTBI prevalence estimates were highest for persons born in Haiti, Peru, Somalia, Ethiopia, Vietnam, and Bhutan, ranging from 42%-55%. LTBI prevalence estimates were lowest for persons born in Colombia, Malaysia, and Thailand, ranging from 8%-13%. CONCLUSIONS: LTBI prevalence in persons born outside the United States varies widely by country. These estimates can help target community outreach efforts to the highest risk groups. |
Optimal testing choice and diagnostic strategies for latent tuberculosis infection among U.S.-born people living with HIV
Pettit AC , Stout JE , Belknap R , Benson CA , Seraphin MN , Lauzardo M , Horne DJ , Garfein RS , Maruri F , Ho CS . Clin Infect Dis 2020 73 (7) e2278-e2284 BACKGROUND: Increased risk of progression from latent tuberculosis infection (LTBI) to tuberculosis (TB) disease among people living with HIV (PLWH) prioritizes them for LTBI testing and treatment. Studies comparing the performance of interferon gamma release assays (IGRAs) and the tuberculin skin test (TST) among PLWH are lacking. METHODS: We used Bayesian latent class analysis to estimate the prevalence of LTBI and diagnostic characteristics of the TST, QuantiFERON Gold In-Tube (QFT), and T.SPOT-TB (TSPOT) among a prospective, multicenter cohort of U.S.-born PLWH ≥5 years old with valid results for all three LTBI tests using standard U.S. cutoffs (≥5mm TST, ≥0.35 IU/mL QFT, ≥8 spots TSPOT). We also explored the performance of varying LTBI test cutoffs. RESULTS: Among 1510 PLWH (median CD4+ count 532 cells/mm3), estimated LTBI prevalence was 4.7%. TSPOT was significantly more specific (99.7%) and had a significantly higher positive predictive value (90.0%, PPV) than QFT (96.5% specificity, 50.7% PPV) and TST (96.8% specificity, 45.4% PPV). QFT was significantly more sensitive (72.2%) than TST (54.2%) and TSPOT (51.9%); negative predictive value of all tests was high (TST 97.7%, QFT 98.6%, TSPOT 97.6%). Even at the highest cutoffs evaluated (15mm TST, ≥1.00 IU/mL QFT, ≥8 spots TSPOT), TST and QFT specificity was significantly lower than TSPOT. CONCLUSIONS: LTBI prevalence among this cohort of U.S.-born PLWH was low compared to non-U.S. born persons. TSPOT's higher PPV may make it preferable for testing U.S.-born PLWH at low risk for TB exposure and with high CD4+ counts. |
Analysis of severe adverse events reported among patients receiving isoniazid-rifapentine treatment for latent Mycobacterium tuberculosis infection - United States, 2012-2016
Schmit KM , Wortham JM , Ho CS , Powell KM . Clin Infect Dis 2020 71 (9) 2502-2505 We analyzed data from 2012-2016 for patients who were hospitalized or who died after >/=1 dose of isoniazid-rifapentine for treatment of latent Mycobacterium tuberculosis infection. No patients died; 15 were hospitalized. Nine patients experienced hypotension and 5 had elevated serum aminotransferases, reinforcing the need for vigilant monitoring during treatment. |
Comparing QuantiFERON-TB Gold Plus with other tests to diagnose Mycobacterium tuberculosis infection.
Venkatappa TK , Punnoose R , Katz DJ , Higgins MP , Banaei N , Graviss EA , Belknap RW , Ho CS . J Clin Microbiol 2019 57 (11) The fourth generation QuantiFERON test for tuberculosis infection, QuantiFERON-TB Gold Plus (QFT-Plus) has replaced the earlier version, QuantiFERON-TB Gold In-Tube (QFT-GIT). A clinical need exists for information about agreement between QFT-Plus and other tests.We conducted this study to assess agreement of test results for QFT-Plus with those of QuantiFERON-TB Gold In-Tube (QFT-GIT), T-SPOT.TB (T-SPOT) and the tuberculin skin test (TST).Persons at high risk of LTBI and/or progression to TB disease were enrolled at the 10 sites of the Tuberculosis Epidemiologic Studies Consortium from October 2016 through May 2017; each participant received all four tests. Cohen's kappa (kappa) and Wilcoxon signed rank test compared qualitative and quantitative results of QFT-Plus with the other tests.Test results for 506 participants showed 94% agreement between QFT-Plus and QFT-GIT, with 19% positive and 75% negative results. When the tests disagreed, it was most often in the direction of QFT-GIT negative/QFT-Plus positive. QFT-Plus had similar concordance as QFT-GIT with TST (77% and 77%) and T-SPOT (92% and 91%), respectively.Conclusions: The study showed high agreement between QFT-GIT and QFT-Plus in a direct comparison. Both tests had similar agreement with TST and T-SPOT. |
Tuberculosis preventive treatment: the next chapter of tuberculosis elimination in India
Moonan PK , Nair SA , Agarwal R , Chadha VK , Dewan PK , Gupta UD , Ho CS , Holtz TH , Kumar AM , Kumar N , Kumar P , Maloney SA , Mase SR , Oeltmann JE , Paramasivan CN , Parmar MM , Rade KK , Ramachandran R , Rao R , Salhorta VS , Sarin R , Sarin S , Sachdeva KS , Selvaraju S , Singla R , Surie D , Tonsing J , Tripathy SP , Khaparde SD . BMJ Glob Health 2018 3 (5) e001135 The End TB Strategy envisions a world free of tuberculosis-zero deaths, disease and suffering due to tuberculosis by 2035. This requires reducing the global tuberculosis incidence from >1250 cases per million people to <100 cases per million people within the next two decades. Expanding testing and treatment of tuberculosis infection is critical to achieving this goal. In high-burden countries, like India, the implementation of tuberculosis preventive treatment (TPT) remains a low priority. In this analysis article, we explore potential challenges and solutions of implementing TPT in India. The next chapter in tuberculosis elimination in India will require cost-effective and sustainable interventions aimed at tuberculosis infection. This will require constant innovation, locally driven solutions to address the diverse and dynamic tuberculosis epidemiology and persistent programme monitoring and evaluation. As new tools, regimens and approaches emerge, midcourse adjustments to policy and practice must be adopted. The development and implementation of new tools and strategies will call for close collaboration between local, national and international partners-both public and private-national health authorities, non-governmental organisations, research community and the diagnostic and pharmaceutical industry. Leading by example, India can contribute to global knowledge through operational research and programmatic implementation for combating tuberculosis infection. |
Evaluating latent tuberculosis infection diagnostics using latent class analysis
Stout JE , Wu Y , Ho CS , Pettit AC , Feng PJ , Katz DJ , Ghosh S , Venkatappa T , Luo R . Thorax 2018 73 (11) 1062-1070 BACKGROUND: Lack of a gold standard for latent TB infection has precluded direct measurement of test characteristics of the tuberculin skin test and interferon-gamma release assays (QuantiFERON Gold In-Tube and T-SPOT.TB). OBJECTIVE: We estimated test sensitivity/specificity and latent TB infection prevalence in a prospective, US-based cohort of 10 740 participants at high risk for latent infection. METHODS: Bayesian latent class analysis was used to estimate test sensitivity/specificity and latent TB infection prevalence among subgroups based on age, foreign birth outside the USA and HIV infection. RESULTS: Latent TB infection prevalence varied from 4.0% among foreign-born, HIV-seronegative persons aged <5 years to 34.0% among foreign-born, HIV-seronegative persons aged >/=5 years. Test sensitivity ranged from 45.8% for the T-SPOT.TB among foreign-born, HIV-seropositive persons aged >/=5 years to 80.7% for the tuberculin skin test among foreign-born, HIV-seronegative persons aged >/=5 years. The skin test was less specific than either interferon-gamma release assay, particularly among foreign-born populations (eg, the skin test had 70.0% specificity among foreign-born, HIV-seronegative persons aged >/=5 years vs 98.5% and 99.3% specificity for the QuantiFERON and T-SPOT.TB, respectively). The tuberculin skin test's positive predictive value ranged from 10.0% among foreign-born children aged <5 years to 69.2% among foreign-born, HIV-seropositive persons aged >/=5 years; the positive predictive values of the QuantiFERON (41.4%) and T-SPOT.TB (77.5%) were also low among US-born, HIV-seropositive persons aged >/=5 years. CONCLUSIONS: These data reinforce guidelines preferring interferon-gamma release assays for foreign-born populations and recommending against screening populations at low risk for latent TB infection. TRIAL REGISTRATION NUMBER: NCT01622140. |
Paradox of serial interferon-gamma release assays: variability width more important than specificity size
Stout JE , Belknap R , Wu YJ , Ho CS . Int J Tuberc Lung Dis 2018 22 (5) 518-523 SETTING: Serial screening for latent tuberculous infection (LTBI) is commonly performed in certain populations, such as health care workers. The high apparent conversion rate in some studies of interferon-gamma release assays is puzzling given the claimed high specificity of these tests. OBJECTIVE: To understand how test-retest variability, specificity, and underlying LTBI prevalence affect observed outcomes of repeated testing for LTBI. DESIGN: Mathematical model assuming constant test sensitivity and specificity over time and no new infections. RESULTS: Test-retest variability had a large effect on the observed proportion of conversions (initial negative test, followed by a positive test) and reversions (initial positive test, followed by a negative test). For example, a test with 70% specificity and 5% test-retest variability would be associated with a conversion rate of 3.7% and a reversion rate of 7.7%, while a test with 95% specificity but 10% test-retest variability would be associated with a conversion rate of 5.5% and a reversion rate of 57%, assuming that both tests are 80% sensitive and underlying LTBI prevalence was 5%. CONCLUSION: Test-retest variability is a key parameter that should be reported for tests used for serial screening for LTBI. Reducing test-retest variability can reduce false-positive and false-negative results. |
High rate of treatment completion in program settings with 12-dose weekly isoniazid and rifapentine (3HP) for latent Mycobacterium tuberculosis infection
Sandul AL , Nwana N , Holcombe JM , Lobato MN , Marks S , Webb R , Wang SH , Stewart B , Griffin P , Hunt G , Shah N , Marco A , Patil N , Mukasa L , Moro RN , Jereb J , Mase S , Chorba T , Bamrah-Morris S , Ho CS . Clin Infect Dis 2017 65 (7) 1085-1093 Background: RCTs demonstrated the newest LTBI regimen, 12 weekly doses of directly observed isoniazid and rifapentine (3HP), as efficacious as 9 months of isoniazid (9H) with a greater completion rate (82% versus 69%); however, 3HP has not been assessed in routine health care settings. Methods: Observational cohort of LTBI patients receiving 3HP through 16 US programs was used to assess treatment completion, adverse drug reactions (ADRs), and factors associated with treatment discontinuation. Results: Of 3288 patients eligible to complete 3HP, 2867 (87.2%) completed treatment. Children 2-17 years had the highest completion rate, 94.5% (155/164). Patients reporting homelessness had a completion rate of 81.2% (147/181). In univariable analyses, discontinuation was lowest among children (relative risk [RR], 0.44 [95% CI, 0.23-0.85]; P = .014), and highest in persons ≥65 years (RR, 1.72 [95% CI, 1.25-2.35] P = .001). In multivariable analyses, discontinuation was lowest among contacts of patients with TB disease (adjusted relative risk [ARR], 0.68 [95% CI, 0.52-0.89]; P = .005), and students (ARR, 0.45 [95% CI, 0.21-0.98]; P = .044); highest with incarceration (ARR, 1.43 [95% CI, 1.08-1.89]; P=.013) and homelessness (ARR, 1.72 [95% CI, 1.25-2.39]; P = .001). ADRs were reported by 1174 (35.7%) patients, of whom 891 (76.0%) completed treatment. Conclusions: Completion of 3HP in routine health care settings was greater overall than rates reported from clinical trials, and greater than historically observed using other regimens among reportedly nonadherent populations. Widespread use of 3HP for LTBI treatment could accelerate elimination of TB disease in the United States. |
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. |
Interferon-gamma release assays and pediatric public health tuberculosis screening: The San Francisco program experience 2005 to 2008
Grinsdale JA , Islam S , Tran OC , Ho CS , Kawamura LM , Higashi JM . J Pediatric Infect Dis Soc 2016 5 (2) 122-30 BACKGROUND: Interferon-gamma release assay utilization in pediatric tuberculosis (TB) screening is limited by a paucity of longitudinal experience, particularly in low-TB burden populations. METHODS: We conducted a retrospective review of QuantiFERON (QFT)-TB Gold results in San Francisco children from 2005 to 2008. Concordance with the tuberculin skin test (TST) was analyzed for a subset of children. Progression to active disease was determined through San Francisco and California TB registry matches. RESULTS: Of 1092 children <15 years of age, 853 (78%) were foreign-born, and 136 (12%) were exposed to active TB cases (contacts). QuantiFERON tests were positive in 72 of 1092 (7%) children; 15 of 136 (11%) recent contacts; 53 of 807 (7%) foreign-born noncontacts; and 4 of 149 (3%) US-born noncontacts. QuantiFERON-negative/TST-positive discordance was seen more often in foreign-born/bacille Calmette-Guerin (BCG)-vaccinated children <5 years of age (52 of 56, 93%) compared to those ≥ 5 years of age (90 of 123, 73%; P = .003). Foreign-born, BCG-vaccinated children were more than twice as likely to have a discordant (79%) result as US-born, non-BCG-vaccinated children (37%; P < .0001). During 5587 person-years of follow-up of untreated children, including 146 TST-positive/QFT-negative children, no cases of active TB were identified, consistent with a negative predictive value of 100%. CONCLUSIONS: Our experience supports the use of QFT to evaluate latent TB infection in children, particularly young BCG-vaccinated children. The proportion of QFT-positive results correlated with risk of exposure, and none of the untreated QFT-negative children developed TB. The low QFT-positive rate highlights the need for more selective testing based on current epidemiology and TB exposure risk. |
Tuberculosis elimination efforts in the United States in the era of insurance expansion and the affordable care act
Balaban V , Marks SM , Etkind SC , Katz DJ , Higashi J , Flood J , Cronina A , Ho CS , Khan A , Chorba T . Public Health Rep 2015 130 (4) 349-354 The Patient Protection and Affordable Care Act can enhance ongoing efforts to control tuberculosis (TB) in the United States by bringing millions of currently uninsured Americans into the health-care system. However, much of the legislative and financial framework that provides essential public health services necessary for effective TB control is outside the scope of the law. We identified three key issues that will still need to be addressed after full implementation of the Affordable Care Act: (1) essential TB-related public health functions will still be needed and will remain the responsibility of federal, state, and local health departments; (2) testing and treatment for latent TB infection (LTBI) is not covered explicitly as a recommended preventive service without cost sharing or copayment; and (3) remaining uninsured populations will disproportionately include groups at high risk for TB. To improve and continue TB control efforts, it is important that all populations at risk be tested and treated for LTBI and TB; that testing and treatment services be accessible and affordable; that essential federal, state, and local public health functions be maintained; that private-sector medical/public health linkages for diagnosis and treatment be developed; and that health-care providers be trained in conducting appropriate LTBI and TB clinical care. |
Interferon-gamma release assays for prediction of tuberculosis
Kawamura LM , Grinsdale JA , Ho CS , Jereb JA . Lancet Infect Dis 2012 12 (8) 584 Molebogeng Rangaka and colleagues1 have comprehensively reviewed the prognostic characteristics of interferon-γ release assays (IGRAs). Their findings show that the advantages of these assays are not offset by any loss of ability to predict development of tuberculosis in people with latent Mycobacterium tuberculosis infection. | Studies that directly compared the assay with the tuberculin skin test confirm the low accuracy of both for estimation of prognosis; tuberculosis will never develop in most people with a positive result from either test, but tuberculosis will develop in some who had negative results. Although the accuracy of both tests is disappointing, IGRAs are no worse—and for some comparisons are better—than tuberculin skin test. | In USA, the benefits of IGRAs support their wide adoption. First, most of our tuberculosis caseload has shifted to BCG-vaccinated immigrant groups, and IGRAs have greater specificity in this group.2 Our experience in San Francisco, CA—where IGRAs have replaced tuberculin skin test in most settings—is that the proportion of immigrants and homeless people with positive test results decreased substantially after switching the in tests (table). The subsequent decrease in medical assessment improves efficiency and cost-effectiveness and fewer patients are inconvenienced by treatment and its toxic effects than if tuberculin skin test was used. The studies reviewed by Rangaka and colleagues report that IGRAs offer these benefits with fewer false-negative results than tuberculin skin test. |
Undiagnosed cases of fatal clostridium-associated toxic shock in Californian women of childbearing age
Ho CS , Bhatnagar J , Cohen AL , Hacker JK , Zane SB , Reagan S , Fischer M , Shieh WJ , Guarner J , Ahmad S , Zaki SR , McDonald LC . Am J Obstet Gynecol 2009 201 (5) 459 e1-7 OBJECTIVE: In 2005, 4 Clostridium sordellii-associated toxic shock fatalities were reported in young Californian women after medical abortions. The true incidence of this rare disease is unknown, and a population-based study has never been performed. Additional clostridia-associated deaths were sought to describe associated clinical characteristics. STUDY DESIGN: Population-based death certificate review and a clinical case definition for clostridial-associated toxic shock identified women with likelihood of dying from a Clostridium infection. Formalin-fixed autopsy tissues underwent immunohistochemical and polymerase chain reaction assays. RESULTS: Thirty-eight women were suspected of having C sordellii-associated death. Five tested positive for Clostridium species: 3 for Clostridium perfringens, 1 for C sordellii, and 1 for both. Deaths occurred after the medical procedures for cervical dysplasia (n = 2), surgical abortion (n = 1), stillborn delivery (n = 1), and term live birth (n = 1). None had a medical abortion. CONCLUSION: C sordellii and C perfringens are associated with undiagnosed catastrophic infectious gynecologic illnesses among women of childbearing age. |
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