Last data update: May 20, 2024. (Total: 46824 publications since 2009)
Records 1-17 (of 17 Records) |
Query Trace: Pai S[original query] |
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Surveillance for rubella virus in samples obtained from non-immunodeficient individuals
Patel S , Russo P , M HR , Maurer K , Hao L , Beard RS , Perelygina L , Sullivan KE . Pediatr Allergy Immunol 2024 35 (1) e14082 |
Global update on the susceptibilities of human influenza viruses to neuraminidase inhibitors and the cap-dependent endonuclease inhibitor baloxavir, 2018-2020.
Govorkova EA , Takashita E , Daniels RS , Fujisaki S , Presser LD , Patel MC , Huang W , Lackenby A , Nguyen HT , Pereyaslov D , Rattigan A , Brown SK , Samaan M , Subbarao K , Wong S , Wang D , Webby RJ , Yen HL , Zhang W , Meijer A , Gubareva LV . Antiviral Res 2022 200 105281 Global analysis of the susceptibility of influenza viruses to neuraminidase (NA) inhibitors (NAIs) and the polymerase acidic (PA) inhibitor (PAI) baloxavir was conducted by five World Health Organization Collaborating Centres for Reference and Research on Influenza during two periods (May 2018-May 2019 and May 2019-May 2020). Combined phenotypic and NA sequence-based analysis revealed that the global frequency of viruses displaying reduced or highly reduced inhibition (RI or HRI) or potential to show RI/HRI by NAIs remained low, 0.5% (165/35045) and 0.6% (159/26010) for the 2018-2019 and 2019-2020 periods, respectively. The most common amino acid substitution was NA-H275Y (N1 numbering) conferring HRI by oseltamivir and peramivir in A(H1N1)pdm09 viruses. Combined phenotypic and PA sequence-based analysis showed that the global frequency of viruses showing reduced susceptibility to baloxavir or carrying substitutions associated with reduced susceptibility was low, 0.5% (72/15906) and 0.1% (18/15692) for the 2018-2019 and 2019-2020 periods, respectively. Most (n = 61) of these viruses had I38→T/F/M/S/L/V PA amino acid substitutions. In Japan, where baloxavir use was highest, the rate was 4.5% (41/919) in the 2018-2019 period and most of the viruses (n = 32) had PA-I38T. Zoonotic viruses isolated from humans (n = 32) in different countries did not contain substitutions in NA associated with NAI RI/HRI phenotypes. One A(H5N6) virus had a dual substitution PA-I38V + PA-E199G, which may reduce susceptibility to baloxavir. Therefore, NAIs and baloxavir remain appropriate choices for the treatment of influenza virus infections, but close monitoring of antiviral susceptibility is warranted. |
Associations of blood lead levels with asthma and blood eosinophils in U.S. children
Cornwell CR , Egan KB , Zahran HS , Mirabelli MC , Hsu J , Chew GL . Pediatr Allergy Immunol 2020 31 (6) 695-699 U.S. children are exposed to lead through lead-based paint, lead-contaminated dust in older homes and through contaminated water, air, soil, or consumer and imported products(1,2) . Approximately 24 million housing units have one or more lead-based paint hazards, including 3.6 million homes with children aged </=6 years(1) . Epidemiologic studies have reported positive associations between lead and elevated immunoglobulin E (IgE) in children(3-5) ; IgE is often associated with allergic asthma(6) . |
Culture cell block controls as a tool to the biomolecular diagnosis of infectious diseases
Jose Tadeu de Araujo L , Salas-Gomez D , Midori Kimura L , Fernandes Possatto Takahashi J , de Souza Barrel J , Rollin DC , Mariotti Guerra J . Appl Immunohistochem Mol Morphol 2019 28 (6) 484-487 The cell block (CB) technique has allowed easy obtainment of samples such as cellular and culture suspensions, to perform specific molecular tests such as immunohistochemistry and in situ hybridization. It has been improved along time, accuracy, and quality of the diagnoses, however, the cost of a commercial gel matrix for the preparation of CB is high and not suitable depending on the situation. The objective of this study is to test agarose as an alternative to the commercial gel matrix in the preparation of Aspergillus fumigatus' CB. |
A systematic review and evaluation of Zika virus forecasting and prediction research during a public health emergency of international concern.
Kobres PY , Chretien JP , Johansson MA , Morgan JJ , Whung PY , Mukundan H , Del Valle SY , Forshey BM , Quandelacy TM , Biggerstaff M , Viboud C , Pollett S . PLoS Negl Trop Dis 2019 13 (10) e0007451 INTRODUCTION: Epidemic forecasting and prediction tools have the potential to provide actionable information in the midst of emerging epidemics. While numerous predictive studies were published during the 2016-2017 Zika Virus (ZIKV) pandemic, it remains unknown how timely, reproducible, and actionable the information produced by these studies was. METHODS: To improve the functional use of mathematical modeling in support of future infectious disease outbreaks, we conducted a systematic review of all ZIKV prediction studies published during the recent ZIKV pandemic using the PRISMA guidelines. Using MEDLINE, EMBASE, and grey literature review, we identified studies that forecasted, predicted, or simulated ecological or epidemiological phenomena related to the Zika pandemic that were published as of March 01, 2017. Eligible studies underwent evaluation of objectives, data sources, methods, timeliness, reproducibility, accessibility, and clarity by independent reviewers. RESULTS: 2034 studies were identified, of which n = 73 met the eligibility criteria. Spatial spread, R0 (basic reproductive number), and epidemic dynamics were most commonly predicted, with few studies predicting Guillain-Barre Syndrome burden (4%), sexual transmission risk (4%), and intervention impact (4%). Most studies specifically examined populations in the Americas (52%), with few African-specific studies (4%). Case count (67%), vector (41%), and demographic data (37%) were the most common data sources. Real-time internet data and pathogen genomic information were used in 7% and 0% of studies, respectively, and social science and behavioral data were typically absent in modeling efforts. Deterministic models were favored over stochastic approaches. Forty percent of studies made model data entirely available, 29% provided all relevant model code, 43% presented uncertainty in all predictions, and 54% provided sufficient methodological detail to allow complete reproducibility. Fifty-one percent of predictions were published after the epidemic peak in the Americas. While the use of preprints improved the accessibility of ZIKV predictions by a median of 119 days sooner than journal publication dates, they were used in only 30% of studies. CONCLUSIONS: Many ZIKV predictions were published during the 2016-2017 pandemic. The accessibility, reproducibility, timeliness, and incorporation of uncertainty in these published predictions varied and indicates there is substantial room for improvement. To enhance the utility of analytical tools for outbreak response it is essential to improve the sharing of model data, code, and preprints for future outbreaks, epidemics, and pandemics. |
Prenatal high molecular weight phthalates and bisphenol A, and childhood respiratory and allergic outcomes
Berger K , Eskenazi B , Balmes J , Kogut K , Holland N , Calafat AM , Harley KG . Pediatr Allergy Immunol 2018 30 (1) 36-46 BACKGROUND: Asthma and allergy prevalence is increasing in United States children. In utero exposure to chemicals used in personal care products and plastics may contribute to increase in these diseases. METHODS: We quantified urinary concentrations of eight phthalate metabolites and bisphenol A in mothers twice during pregnancy in 1999-2000 in Salinas, California. We assessed probable asthma, aeroallergies, eczema, and spirometry in their age 7 children, and measured T helper 1 and T helper 2 cells in blood at ages 2, 5, and 7 (N=392). We employed Bayesian Model Averaging to select confounders from additional biomarkers measured in this population and controlled for them in logistic and linear regressions. RESULTS: Monocarboxyisooctyl phthalate was associated with increased odds for probable asthma (odds ratio: 1.54, 95% CI: 1.12, 2.12), and with lower forced expiratory volume in one second (beta: -0.09 liters, 95% CI: -0.15, -0.03) and forced expiratory flow from 25-75% of forced vital capacity (beta: -7.06 liters/second, 95% CI: -11.04, -2.90). Several other associations were attenuated in final models that controlled for additional biomarkers. CONCLUSION: Monocarboxyisooctyl phthalate was associated with lower respiratory health after controlling for related chemical exposure, which suggests that confounding by multiple chemical exposures should be considered in future research. This article is protected by copyright. All rights reserved. |
Official American Thoracic Society/Infectious Diseases Society of America/Centers for Disease Control and Prevention Clinical Practice Guidelines: Diagnosis of tuberculosis in adults and children
Lewinsohn DM , Leonard MK , LoBue PA , Cohn DL , Daley CL , Desmond E , Keane J , Lewinsohn DA , Loeffler AM , Mazurek GH , O'Brien RJ , Pai M , Richeldi L , Salfinger M , Shinnick TM , Sterling TR , Warshauer DM , Woods GL . Clin Infect Dis 2017 64 (2) 111-115 BACKGROUND: Individuals infected with Mycobacterium tuberculosis (Mtb) may develop symptoms and signs of disease (tuberculosis disease) or may have no clinical evidence of disease (latent tuberculosis infection [LTBI]). Tuberculosis disease is a leading cause of infectious disease morbidity and mortality worldwide, yet many questions related to its diagnosis remain. METHODS: A task force supported by the American Thoracic Society, Centers for Disease Control and Prevention, and Infectious Diseases Society of America searched, selected, and synthesized relevant evidence. The evidence was then used as the basis for recommendations about the diagnosis of tuberculosis disease and LTBI in adults and children. The recommendations were formulated, written, and graded using the Grading, Recommendations, Assessment, Development and Evaluation (GRADE) approach. RESULTS: Twenty-three evidence-based recommendations about diagnostic testing for latent tuberculosis infection, pulmonary tuberculosis, and extrapulmonary tuberculosis are provided. Six of the recommendations are strong, whereas the remaining 17 are conditional. CONCLUSIONS: These guidelines are not intended to impose a standard of care. They provide the basis for rational decisions in the diagnosis of tuberculosis in the context of the existing evidence. No guidelines can take into account all of the often compelling unique individual clinical circumstances. |
NHF-McMaster guideline on care models for haemophilia management
Pai M , Key NS , Skinner M , Curtis R , Feinstein M , Kessler C , Lane SJ , Makris M , Riker E , Santesso N , Soucie JM , Yeung CH , Iorio A , Schunemann HJ . Haemophilia 2016 22 Suppl 3 6-16 This guideline was developed to identify evidence-based best practices in haemophilia care delivery, and discuss the range of care providers and services that are most important to optimize outcomes for persons with haemophilia (PWH) across the United States. The guideline was developed following specific methods described in detail in this supplement and based on the GRADE (Grading of Recommendations, Assessment, Development and Evaluation approach). Direct evidence from published literature and the haemophilia community, as well as indirect evidence from other chronic diseases, were reviewed, synthesized and applied to create evidence-based recommendations. The Guideline panel suggests that the integrated care model be used over non-integrated care models for PWH (conditional recommendation, moderate certainty in the evidence). For PWH with inhibitors and those at high risk for inhibitor development, the same recommendation was graded as strong, with moderate certainty in the evidence. The panel suggests that a haematologist, a specialized haemophilia nurse, a physical therapist, a social worker and round-the-clock access to a specialized coagulation laboratory be part of the integrated care team, over an integrated care team that does not include all of these components (conditional recommendation, very low certainty in the evidence). Based on available evidence, the integrated model of care in its current structure, is suggested for optimal care of PWH. There is a need for further appropriately designed studies that address unanswered questions about specific outcomes and the optimal structure of the integrated care delivery model in haemophilia. |
Care models in the management of haemophilia: A systematic review
Yeung CH , Santesso N , Pai M , Kessler C , Key NS , Makris M , Navarro-Ruan T , Soucie JM , Schunemann HJ , Iorio A . Haemophilia 2016 22 Suppl 3 31-40 BACKGROUND: Haemophilia care is commonly provided via multidisciplinary specialized management. To date, there has been no systematic assessment of the impact of haemophilia care delivery models on patient-important outcomes. OBJECTIVE: To conduct a systematic review of published studies assessing the effects of the integrated care model for persons with haemophilia (PWH). SEARCH METHODS: We searched MEDLINE, EMBASE and CINAHL up to April 22, 2015, contacted experts in the field, and reviewed reference lists. SELECTION CRITERIA: Randomized and non-randomized studies of PWH or carriers, focusing mainly on the assessment of care models on delivery. DATA COLLECTION AND ANALYSIS: Two investigators independently screened title, abstract, and full text of retrieved articles for inclusion. Risk of bias and overall quality of evidence was assessed using Cochrane's ACROBAT-NRSI tool and GRADE respectively. Relative risks, mean differences, proportions, and means and their variability were calculated as appropriate. RESULTS: 27 non-randomized studies were included: eight comparative and 19 non-comparative studies. We found low- to very low-quality evidence that in comparison to other models of care, integrated care may reduce mortality, hospitalizations and emergency room visits, may lead to fewer missed days of school and work, and may increase knowledge seeking. CONCLUSION: Our comprehensive review found low- to very low-quality evidence from a limited number of non-randomized studies assessing the impact of haemophilia care models on some patient-important outcomes. While the available evidence suggests that adoption of the integrated care model may provide benefit to PWH, further high-quality research in the field is needed. |
Defining the needs for next generation assays for tuberculosis
Denkinger CM , Kik SV , Cirillo DM , Casenghi M , Shinnick T , Weyer K , Gilpin C , Boehme CC , Schito M , Kimerling M , Pai M . J Infect Dis 2015 211 S29-s38 To accelerate the fight against tuberculosis, major diagnostic challenges need to be addressed urgently. Post-2015 targets are unlikely to be met without the use of novel diagnostics that are more accurate and can be used closer to where patients first seek care in affordable diagnostic algorithms. This article describes the efforts by the stakeholder community that led to the identification of the high-priority diagnostic needs in tuberculosis. Subsequently target product profiles for the high-priority diagnostic needs were developed and reviewed in a World Health Organization (WHO)-led consensus meeting. The high-priority diagnostic needs included (1) a sputum-based replacement test for smear-microscopy; (2) a non-sputum-based biomarker test for all forms of tuberculosis, ideally suitable for use at levels below microscopy centers; (3) a simple, low cost triage test for use by first-contact care providers as a rule-out test, ideally suitable for use by community health workers; and (4) a rapid drug susceptibility test for use at the microscopy center level. The developed target product profiles, along with complimentary work presented in this supplement, will help to facilitate the interaction between the tuberculosis community and the diagnostics industry with the goal to lead the way toward the post-2015 global tuberculosis targets. |
Examination of genetic variants involved in generation and biodisposition of kinins in patients with angioedema
Levy J , Rivard GE , Wagner E , Beezhold D , Berlin N , Fan L , Zhang Z , Sussman GL . Allergy Asthma Clin Immunol 2014 10 (1) 60 BACKGROUND: Angioedema (AE) is idiopathic in the majority of cases. We studied patients with AE for genetic variants of proteins involved with bradykinin generation and biodisposition. METHODS: One hundred sixty one patients with AE were recruited at a university hospital clinic. Patients were categorized according to the proposed pathogenesis of AE: low C1 inhibitor (C1-INH) and C4 levels, autoimmune disease, cancer, angiotensin-converting enzyme (ACE) inhibitor-induced, nonsteroidal antiinflammatory drug (NSAID)-induced, or idiopathic. In addition, each patient had a blood sample analyzed for a complement profile and enzymes (C1-INH and C4). Fifty-two of the patients were tested for genetic variants in factor XII, plasminogen-activator inhibitor-1 (PAI-1), ACE, and aminopeptidase P (APP). RESULTS: The cause of angioedema was identified in 59/161 (37%) of the cases: 3 (2%) patients had a low plasma C1-INH and C4; 20 (12%) were ACE inhibitor-induced; 12 (7%) were associated with autoimmune disorders; 7 (4%) were associated with malignancy; and 17 (11%) were associated with NSAIDs. In the remaining 102 (63%) patients the cause of angioedema was idiopathic. Of 52 patients with genetic analysis, 13 (25%) had a genetic variant in APP, 10 (19%) in ACE, 13 (25%) in PAI-1, and 0 in Factor XII. CONCLUSIONS: In addition to related diseases and medications causing AE, certain genetic variants encoding proteins involved in bradykinin generation and/or catabolism pathways may be involved in the pathogenesis of AE. |
Point-of-care tests for HIV, related coinfections, and blood-borne infections
Pant Pai N , Peeling RW , Smith BD , Dowdy D . AIDS Res Treat 2014 2014 625082 In the past 2 decades, rapid and point-of-care tests (POCTs) for HIV have facilitated a rapid increase in the uptake of HIV testing in sub-Saharan Africa, Asia, and the United States. POCTs for HIV are now commercially available to either detect early infection or ascertain degree of immunosuppression and monitor disease progression, thereby improving patient management. Some rapid HIV tests have evolved into POCTs, and some POCTs have even progressed into over-the-counter self- or home-based tests. In addition to the availability of unique rapid tests for hepatitis C, hepatitis B, and syphilis, multiplexed POCTs can now detect these infections using a single point-of-care device. Integration of POCT with other technologies has further expanded our ability to test and treat HIV coinfections and reduce morbidity and mortality due to HIV coinfections. For example, many POCTs for hepatitis C, hepatitis B, and syphilis are now as accurate compared to laboratory-based first-line tests, offering hope of expanded access to the millions that desire timely screening in outreach settings. In addition, novel tools like CD4 POC assays that have shown promising accuracy now offer hope of expedited triage and staging for antiretroviral treatment initiation. Timely testing and treatment will further reduce loss to followup of patients. | A quick evolution in rapid and POCT technology has catalyzed global research and policy. Implementation research with rapid and POC tests has strived to integrate some of these developments. The focus is shifting to novel testing strategies and programs that have been pilot-tested in different parts of the world, thereby offering hope of expanded access, improved patient engagement, and efficient service delivery in the times to come. |
Multidrug resistant pulmonary tuberculosis treatment regimens and patient outcomes: an individual patient data meta-analysis of 9,153 patients
Ahuja SD , Ashkin D , Avendano M , Banerjee R , Bauer M , Bayona JN , Becerra MC , Benedetti A , Burgos M , Centis R , Chan ED , Chiang CY , Cox H , D'Ambrosio L , Deriemer K , Dung NH , Enarson D , Falzon D , Flanagan K , Flood J , Garcia-Garcia ML , Gandhi N , Granich RM , Hollm-Delgado MG , Holtz TH , Iseman MD , Jarlsberg LG , Keshavjee S , Kim HR , Koh WJ , Lancaster J , Lange C , de Lange WC , Leimane V , Leung CC , Li J , Menzies D , Migliori GB , Mishustin SP , Mitnick CD , Narita M , O'Riordan P , Pai M , Palmero D , Park SK , Pasvol G , Pena J , Perez-Guzman C , Quelapio MI , Ponce-de-Leon A , Riekstina V , Robert J , Royce S , Schaaf HS , Seung KJ , Shah L , Shim TS , Shin SS , Shiraishi Y , Sifuentes-Osornio J , Sotgiu G , Strand MJ , Tabarsi P , Tupasi TE , van Altena R , Van der Walt M , Van der Werf TS , Vargas MH , Viiklepp P , Westenhouse J , Yew WW , Yim JJ . PLoS Med 2012 9 (8) e1001300 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.) |
Ultrafiltration improves ELISA and Endopep MS analysis of botulinum neurotoxin type A in drinking water
Raphael BH , Lautenschlager M , Kahler A , Pai S , Parks BA , Kalb SR , Maslanka SE , Shah S , Magnuson M , Hill V . J Microbiol Methods 2012 90 (3) 267-72 The objective of this study was to adapt and evaluate two in vitro botulinum neurotoxin (BoNT) detection methods, including the Botulinum Toxin ELISA and the Endopep MS (a mass spectrometric-based endopeptidase method), for use with drinking water samples. The method detection limits (MDL) of the ELISA and Endopep MS were 260pg/mL and 21pg/mL of BoNT/A complex toxin, respectively. Since toxin could be present in water samples at highly dilute concentrations, large volume (100-L) samples of municipal tap water from five US municipalities having distinct water compositions were dechlorinated, spiked with 5mcg BoNT/A, and subjected to tangential-flow ultrafiltration (UF) using hollow fiber dialyzers. The recovery efficiency of BoNT/A using UF and quantified by ELISA ranged from 11% to 36% while efficiencies quantified by MS ranged from 26% to 55%. BoNT/A was shown to be stable in dechlorinated municipal tap water stored at 4 degrees C for up to four weeks. In addition, toxin present in UF-concentrated water samples was also shown to be stable at 4 degrees C for up to four weeks, allowing holding of samples prior to analysis. Finally, UF was used to concentrate a level of toxin (7pg/mL) which is below the MDL for direct analysis by both ELISA and Endopep MS. Following UF, toxin was detectable in these samples using both in vitro analysis methods. These data demonstrate that UF-concentration of toxin from large volume water samples followed by use of existing analytical methods for detection of BoNT/A can be used in support of a monitoring program for contaminants in drinking water. |
Interferon-gamma release assays for the diagnosis of latent tuberculosis infection in HIV-infected individuals - a systematic review and meta-analysis
Cattamanchi A , Smith R , Steingart KR , Metcalfe JZ , Date A , Coleman C , Marston BJ , Huang L , Hopewell PC , Pai M . J Acquir Immune Defic Syndr 2010 56 (3) 230-8 OBJECTIVE: To determine whether interferon-gamma release assays (IGRAs) improve the identification of HIV-infected individuals who could benefit from LTBI therapy. DESIGN: Systematic review and meta-analysis. METHODS: We searched multiple databases through May 2010 for studies evaluating the performance of the newest commercial IGRAs (QuantiFERON-Gold In-tube [QFT-GIT] and T-SPOT.TB [TSPOT]) in HIV-infected individuals. We assessed the quality of all studies included in the review, summarized results in pre-specified sub-groups using forest plots, and where appropriate, calculated pooled estimates using random effects models. RESULTS: The search identified 37 studies that included 5736 HIV-infected individuals. In 3 longitudinal studies, the risk of active TB was higher in HIV-infected individuals with positive versus negative IGRA results. However, the risk difference was not statistically significant in the 2 studies that reported IGRA results according to manufacturer-recommended criteria. In persons with active TB (a surrogate reference standard for LTBI), pooled sensitivity estimates were heterogeneous, but higher for TSPOT (72%, 95% CI 62-81%) than for QFT-GIT (61%, 95% CI 41-75%). However, neither IGRA was consistently more sensitive than the tuberculin skin test (TST) in head-to-head comparisons. While TSPOT appeared to be less affected by immunosuppression than QFT-GIT and TST, overall, differences between the three tests were small or inconclusive. CONCLUSIONS: Current evidence suggests that IGRAs perform similarly to the TST at identifying HIV-infected individuals with LTBI. Given that both tests have modest predictive value and sub-optimal sensitivity, the decision to use either test should be based on country guidelines and resource and logistical considerations. |
Standardized treatment of active tuberculosis in patients with previous treatment and/or with mono-resistance to isoniazid: a systematic review and meta-analysis
Menzies D , Benedetti A , Paydar A , Royce S , Pai M , Burman W , Vernon A , Lienhardt C . PLoS Med 2009 6 (9) e1000150 BACKGROUND: A standardized regimen recommended by the World Health Organization for retreatment of active tuberculosis (TB) is widely used, but treatment outcomes are suspected to be poor. We conducted a systematic review of published evidence of treatment of patients with a history of previous treatment or documented isoniazid mono-resistance. METHODS AND FINDINGS: PubMed, EMBASE, and the Cochrane Central database for clinical trials were searched for randomized trials in previously treated patients and/or those with with mono-resistance to isoniazid, published in English, French, or Spanish between 1965 and June 2008. The first two sources were also searched for cohort studies evaluating specifically the current retreatment regimen. In studies selected for inclusion, rifampin-containing regimens were used to treat patients with bacteriologically confirmed pulmonary TB, in whom bacteriologically confirmed failure and/or relapse had been reported. Pooled cumulative incidences and 95% CIs of treatment outcomes were computed with random effects meta-analyses and negative binomial regression. No randomized trials of the currently recommended retreatment regimen were identified. Only six cohort studies were identified, in which failure rates were 18%-44% in those with isoniazid resistance. In nine trials, using very different regimens in previously treated patients with mono-resistance to isoniazid, the combined failure and relapse rates ranged from 0% to over 75%. From pooled analysis of 33 trials in 1,907 patients with mono-resistance to isoniazid, lower failure, relapse, and acquired drug resistance rates were associated with longer duration of rifampin, use of streptomycin, daily therapy initially, and treatment with a greater number of effective drugs. CONCLUSIONS: There are few published studies to support use of the current standardized retreatment regimen. Randomized trials of treatment of persons with isoniazid mono-resistance and/or a history of previous TB treatment are urgently needed. |
Effect of duration and intermittency of rifampin on tuberculosis treatment outcomes: a systematic review and meta-analysis
Menzies D , Benedetti A , Paydar A , Martin I , Royce S , Pai M , Vernon A , Lienhardt C , Burman W . PLoS Med 2009 6 (9) e1000146 BACKGROUND: Treatment regimens for active tuberculosis (TB) that are intermittent, or use rifampin during only the initial phase, offer practical advantages, but their efficacy has been questioned. We conducted a systematic review of treatment regimens for active TB, to assess the effect of duration and intermittency of rifampin use on TB treatment outcomes. METHODS AND FINDINGS: PubMed, Embase, and the Cochrane CENTRAL database for clinical trials were searched for randomized controlled trials, published in English, French, or Spanish, between 1965 and June 2008. Selected studies utilized standardized treatment with rifampin-containing regimens. Studies reported bacteriologically confirmed failure and/or relapse in previously untreated patients with bacteriologically confirmed pulmonary TB. Pooled cumulative incidences of treatment outcomes and association with risk factors were computed with stratified random effects meta-analyses. Meta-regression was performed using a negative binomial regression model. A total of 57 trials with 312 arms and 21,472 participants were included in the analysis. Regimens utilizing rifampin only for the first 1-2 mo had significantly higher rates of failure, relapse, and acquired drug resistance, as compared to regimens that used rifampin for 6 mo. This was particularly evident when there was initial drug resistance to isoniazid, streptomycin, or both. On the other hand, there was little evidence of difference in failure or relapse with daily or intermittent schedules of treatment administration, although there was insufficient published evidence of the efficacy of twice-weekly rifampin administration throughout therapy. CONCLUSIONS: TB treatment outcomes were significantly worse with shorter duration of rifampin, or with initial drug resistance to isoniazid and/or streptomycin. Treatment outcomes were similar with all intermittent schedules evaluated, but there is insufficient evidence to support administration of treatment twice weekly throughout therapy. |
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