Publications by authors named "Hongjo Choi"

22 Publications

  • Page 1 of 1

Evaluating the impact of the nationwide public-private mix (PPM) program for tuberculosis under National Health Insurance in South Korea: A difference in differences analysis.

PLoS Med 2021 Jul 14;18(7):e1003717. Epub 2021 Jul 14.

Korean Institute of Tuberculosis, Korean National Tuberculosis Association, Cheongju, Republic of Korea.

Background: Public-private mix (PPM) programs on tuberculosis (TB) have a critical role in engaging and integrating the private sector into the national TB control efforts in order to meet the End TB Strategy targets. South Korea's PPM program can provide important insights on the long-term impact and policy gaps in the development and expansion of PPM as a nationwide program.

Methods And Findings: Healthcare is privatized in South Korea, and a majority (80.3% in 2009) of TB patients sought care in the private sector. Since 2009, South Korea has rapidly expanded its PPM program coverage under the National Health Insurance (NHI) scheme as a formal national program with dedicated PPM nurses managing TB patients in both the private and public sectors. Using the difference in differences (DID) analytic framework, we compared relative changes in TB treatment outcomes-treatment success (TS) and loss to follow-up (LTFU)-in the private and public sector between the 2009 and 2014 TB patient cohorts. Propensity score matching (PSM) using the kernel method was done to adjust for imbalances in the covariates between the 2 population cohorts. The 2009 cohort included 6,195 (63.0% male, 37.0% female; mean age: 42.1) and 27,396 (56.1% male, 43.9% female; mean age: 45.7) TB patients in the public and private sectors, respectively. The 2014 cohort included 2,803 (63.2% male, 36.8% female; mean age: 50.1) and 29,988 (56.5% male, 43.5% female; mean age: 54.7) patients. In both the private and public sectors, the proportion of patients with transfer history decreased (public: 23.8% to 21.7% and private: 20.8% to 17.6%), and bacteriological confirmed disease increased (public: 48.9% to 62.3% and private: 48.8% to 58.1%) in 2014 compared to 2009. After expanding nationwide PPM, absolute TS rates improved by 9.10% (87.5% to 93.4%) and by 13.6% (from 70.3% to 83.9%) in the public and private sectors. Relative to the public, the private saw 4.1% (95% confidence interval [CI] 2.9% to 5.3%, p-value < 0.001) and -8.7% (95% CI -9.7% to -7.7%, p-value <0.001) higher rates of improvement in TS and reduction in LTFU. Treatment outcomes did not improve in patients who experienced at least 1 transfer during their TB treatment. Study limitations include non-longitudinal nature of our original dataset, inability to assess the regional disparities, and verify PPM program's impact on TB mortality.

Conclusions: We found that the nationwide scale-up of the PPM program was associated with improvements in TB treatment outcomes in the private sector in South Korea. Centralized financial governance and regulatory mechanisms were integral in facilitating the integration of highly diverse South Korean private sector into the national TB control program and scaling up of the PPM intervention nationwide. However, TB care gaps continued to exist for patients who transferred at least once during their treatment. These programmatic gaps may be improved through reducing administrative hurdles and making programmatic amendments that can help facilitate management TB patients between institutions and healthcare sectors, as well as across administrative regions.
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http://dx.doi.org/10.1371/journal.pmed.1003717DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8318235PMC
July 2021

Tuberculosis: A persistent unpleasant neighbour of humans.

J Infect Public Health 2021 Apr 11;14(4):508-513. Epub 2021 Jan 11.

Department of Mycobacterium Reference and Research, Research Institute of Tuberculosis, Japan Anti-Tuberculosis Association, 3-1-24 Matsuyama, Kiyose-shi, Tokyo 204-8533, Japan. Electronic address:

Mycobacterium tuberculosis, the bacterium that causes tuberculosis, has long been an unpleasant neighbour of humans. Following transmission of the bacterium from patients with active infection, new hosts do not immediately develop symptoms, as M. tuberculosis initially remains quiescent. However, it is eventually triggered, leading to the infection of other individuals. Humans are the exclusive host, and the rapid proliferation of the human population worldwide along with increasing globalisation have contributed to the pathogen's persistence, as have the survival strategies employed by M. tuberculosis, especially its resistance to several antimicrobials. Defeating this enemy will require novel approaches.
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http://dx.doi.org/10.1016/j.jiph.2021.01.005DOI Listing
April 2021

Mainstreaming of Health Equity in Infectious Disease Control Policy During the COVID-19 Pandemic Era.

J Prev Med Public Health 2021 Jan 15;54(1):1-7. Epub 2021 Jan 15.

People's Health Institute, Seoul, Korea.

The Korean government's strategy to combat coronavirus disease 2019 (COVID-19) has focused on non-pharmaceutical interventions, such as social distancing and wearing masks, along with testing, tracing, and treatment; overall, its performance has been relatively good compared to that of many other countries heavily affected by COVID-19. However, little attention has been paid to health equity in measures to control the COVID-19 pandemic. The study aimed to examine the unequal impacts of COVID-19 across socioeconomic groups and to suggest potential solutions to tackle these inequalities. The pathways linking social determinants and health could be entry points to tackle the unequal consequences of this public health emergency. It is crucial for infectious disease policy to consider social determinants of health including poor housing, precarious working conditions, disrupted healthcare services, and suspension of social services. Moreover, the high levels of uncertainty and complexity inherent in this public health emergency, as well as the health and socioeconomic inequalities caused by the pandemic, underscore the need for good governance other than top-down measures by the government. We emphasize that a people-centered perspective is a key approach during the pandemic era. Mutual trust between the state and civil society, strong accountability of the government, and civic participation are essential components of cooperative disaster governance.
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http://dx.doi.org/10.3961/jpmph.20.593DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7939756PMC
January 2021

Protocol of a Nationwide Observational Study among Patients with Nontuberculous Mycobacterium Pulmonary Disease in South Korea (NTM-KOREA).

Tuberc Respir Dis (Seoul) 2020 Apr 10;83(2):141-146. Epub 2020 Mar 10.

Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.

Background: The burden of nontuberculous mycobacterial (NTM) pulmonary disease (PD) is increasing globally. To understand the treatment outcomes and prognosis of NTM-PD, a unified registry is needed. In this project, we aim to construct a multicenter prospective observational cohort with NTM-PD in South Korea (NTM-KOREA).

Methods: The primary objective of this study is to analyze treatment outcomes according to the species. In addition, recurrence rate, adverse events, the impact of each drug on treatment outcomes as well as the impact of characteristics of mycobacteriology will be analyzed. The inclusion criteria for the study are as follows: fulfilling the criteria for NTM-PD having one of the following etiologic organisms: complex, subspecies , subspecies , or ; receiving the first treatment for NTM-PD after enrollment; age >20 years; and consenting to participate in the study. Seven institutions will participate in patient enrollment and about 500 patients are expected to be enrolled. Participants will be recruited from 1 March 2020 until 19 March 2024 and will be observed through 19 March 2029. During the follow-up period, participants' clinical course will be tracked and their clinical data as well as NTM isolates will be collected.

Conclusion: NTM-KOREA will be the first nationwide observational cohort for NTM-PD in South Korea. It will provide the information to optimize treatment modalities and will contribute to deeper understanding of the treatment outcomes and long-term prognosis of patients with NTM-PD in South Korea.
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http://dx.doi.org/10.4046/trd.2019.0077DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7105436PMC
April 2020

Effects of particulate air pollution on tuberculosis development in seven major cities of Korea from 2010 to 2016: methodological considerations involving long-term exposure and time lag.

Epidemiol Health 2020 12;42:e2020012. Epub 2020 Mar 12.

Research Center, the Korean Institute of Tuberculosis, Korean National Tuberculosis Association, Seoul, Korea.

Objectives: Epidemiological evidence of associations between ambient particulate matter (PM) and tuberculosis (TB) risk is accumulating. Two previous studies in Korea found associations between air pollution-especially sulfur dioxide (SO2)-and TB. In this study, we conducted an annual time-series cross-sectional study to assess the effect of PM with an aerodynamic diameter less than 10 μm (PM10) on TB risk in seven major cities of Korea from 2010 to 2016, taking into account time lag and long-term cumulative exposure.

Methods: Age-standardized TB notification rates were derived using the Korea National TB Surveillance System. Annual average PM10 concentrations were obtained from annual Korean air quality reports. We applied a generalized linear mixed model with unconstrained distributed lags of exposure to PM10. We adjusted for potential confounders such as age, health behaviors, and area-level characteristics.

Results: Both average annual PM10 concentrations and age-standardized TB notification rates decreased over time. The association between cumulative exposure to PM10 and TB incidence became stronger as a longer exposure duration was considered. An increase of one standard deviation (5.63 μg/m3) in PM10 exposure for six years was associated with a 1.20 (95% confidence interval, 1.17 to 1.22) times higher TB notification rate. The marginal association of exposure duration with the TB notification rate was highest at four and five years prior to TB notification. This association remained consistent even after adjusting it for exposure to SO2.

Conclusions: The findings of this study suggest that cumulative exposure to PM10 may affect TB risk, with a potential lag effect.
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http://dx.doi.org/10.4178/epih.e2020012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7285441PMC
April 2020

Impact of Housing Provision Package on Treatment Outcome Among Homeless Tuberculosis Patients in South Korea.

Asia Pac J Public Health 2019 10 14;31(7):603-611. Epub 2019 Sep 14.

Korea University, Seoul, Republic of Korea.

The objective of this study was to assess the effect of a housing provision package on treatment outcomes among homeless South Korean tuberculosis (TB) patients. We conducted a prospective, single-arm, community-based study with historical controls as follows: community-based intervention group (COM), who were provided housing, nutrition, and case management, and received directly observed therapy services; a first historical control that was treated as usual (TAU); and a second historical control that comprised homeless TB patients residing in long-term TB-care facility (FAC). A multivariable logistic regression model was constructed to identify predictors associated with treatment success among homeless TB patients. Treatment was successful in 86.0%, 58.3%, and 96.1% of patients in the COM, TAU, and FAC groups, respectively. Interventions, including those found in the COM and FAC groups, were the only predictors of treatment success. Therefore, we determined that housing provision package positively influenced the treatment outcomes of homeless TB patients.
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http://dx.doi.org/10.1177/1010539519871779DOI Listing
October 2019

Social selection in historical time: The case of tuberculosis in South Korea after the East Asian financial crisis.

PLoS One 2019 16;14(5):e0217055. Epub 2019 May 16.

Bloomberg Faculty of Nursing, University of Toronto, Toronto, Ontario, Canada.

The perspectives of social selection and causation have long been debated. Social selection theory is as "social" as social causation theory, since all diseases are social and no biological process occurs outside society. To identify the social selection pathway and historical juncture affected by socioeconomic and political changes, we investigated the reciprocal impact of suffering from tuberculosis (TB) on the current socioeconomic position (SEP), stratified by childhood SEP. We also examined the extent to which the social consequences of ill health changed since the East Asian economic downturn. Data were collected for 2007-2012 from the Korea National Health and Nutritional Examination Survey. To identify associations between TB history and current household income (HHI), we constructed an ordinal logistic regression model adjusted for covariates, including age, gender, educational attainment, and job status. We adopted a recursive regression model to examine trend changes in this association from 1980-2012 to 2003-2012. Of 28,136 participants, 936 had experienced TB. In the first ordinal logistic regression, the TB group was more likely to have lower HHI than the non-TB group. The odds ratios (ORs) increased from 1.30 (1980-2012) to 1.86 (2003-2012) for the TB group, increasing their probability of having low HHI. Among the low childhood SEP group, the TB group's probability of having low HHI was 1.35 (95% confidence interval [CI]: 1.16-1.57) during 1980-2012, which increased to 2.01 (95% CI: 1.37-2.95) during 2003-2012. For the high childhood SEP group, the TB group's OR range fluctuated, similar to that for the non-TB group. The results support the social selection pathway from TB history to adverse impact on current SEP. Our study identified downward social mobility due to TB history among the low childhood SEP group. Moreover, negative social consequences deteriorated since the East Asian economic crisis.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0217055PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6522038PMC
February 2020

A Pilot Project of Systematic Tuberculosis Screening in the Elderly in a South Korean Province.

Tuberc Respir Dis (Seoul) 2019 Jul 28;82(3):194-200. Epub 2019 Feb 28.

Department of Research and Development, The Korean Institute of Tuberculosis, Korean National Tuberculosis Association, Cheongju, Korea.

Background: Tuberculosis (TB) is a major infectious disease in South Korea causing substantial disease burden, particularly in the elderly. This study aimed to identify the case detection rate of mobile TB screening for the elderly conducted in the Jeollanam-do region and to analyze risk factors of active TB.

Methods: We screened the elderly population (≥65 years old) in Jeollanam-do from August to December 2017. Chest radiography was performed for all participants. Participants with TB presumptive signs were asked to submit sputum specimen(s). Sputum smear, culture, and polymerase chain reaction analyses were performed. Cascade analysis, chi-squared tests, and Fisher exact tests were used to evaluate screening performance.

Results: In total, 12,402 participants were screened, and 211 (1.7%) were suspected to have active TB; 181 of the suspected patients (85.8%) underwent sputum smear test, and 16 (8.8%) patients were confirmed to have TB. The TB prevalence among the elderly was bacteriologically confirmed to be 129 per 100,000 individuals, which was similar to national TB notification data for the same age groups. The proportion of active TB cases increased with age, and differed based on sex and past TB history. However, TB-related symptoms, comorbidity status, and TB screening history within 12 months were not predictive of active TB.

Conclusion: This study identified that the prevalence rate was similar to national TB notification data from the same age groups. Periodic, community-based, systematic TB screening among the elderly population is recommended.
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http://dx.doi.org/10.4046/trd.2018.0063DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6609519PMC
July 2019

Investigation of false-positive culture tests using whole genome sequencing.

Ann Thorac Med 2019 Jan-Mar;14(1):90-93

Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Chungbuk National University Hospital, Cheongju, Republic of Korea.

Although accurate identification of is the gold standard for tuberculosis (TB) diagnosis, there have been several reports of false-positive results. After identifying a sudden increase in extensively drug-resistant TB, false-positive mycobacterial culture tests were suspected, and we contacted the supranational reference center for molecular typing. genotyping tests showed that isolates from all five patients had an identical genotype pattern, and all harbored the same Beijing strain based on sequence-based phylogenic analysis and drug-resistant single nucleotide polymorphisms (SNPs) analysis. We also used whole genome sequencing (WGS) to compare the SNPs of all isolates with a reference genome, and all were identical. We adapted WGS to efficiently detect false-positive MTB culture tests.
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http://dx.doi.org/10.4103/atm.ATM_184_18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6341868PMC
February 2019

Association of social deprivation and outdoor air pollution with pulmonary tuberculosis in spatiotemporal analysis.

Int J Environ Health Res 2019 Dec 30;29(6):657-667. Epub 2019 Jan 30.

Department of Public Health Sciences, Graduate School of Korea University, BK21Plus Program in Public Health Sciences , Seoul , Republic of Korea.

The objective of this study was to identify the association between social deprivation, outdoor air pollution, and tuberculosis (TB) incidence rate or mortality rate. The study sample comprised 25 districts in Seoul, Korea. We used two public data derived from the Community Health Survey and Seoul Statistics. The geographic information system analysis and random effects Poisson regression were applied to explore the association of social deprivation and air pollution with TB incidence and mortality. An 1 ppb increase in sulfur dioxide (SO) concentration was significantly associated with the risk of TB incidence (risk ratio [RR] = 1.046, 95% confidence interval [CI]: 1.028, 1.065). An 1 unit increase in the deprivation index was significantly related to a6% increase in the mortality of TB (RR = 1.063, 95% CI: 1.031, 1.097). : Our results imply that social deprivation and air pollution may affect the different TB outcomes. Effective policy-making for TB control should reflect the differing outcomes between TB incidence and mortality.
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http://dx.doi.org/10.1080/09603123.2019.1566522DOI Listing
December 2019

Action towards Universal Health Coverage and Social Protection for Tuberculosis Care and Prevention: Workshop on the End TB Strategy Pillar 2 in the Western Pacific Region 2017.

Trop Med Infect Dis 2018 Dec 24;4(1). Epub 2018 Dec 24.

Ministry of Labour-Invalids and Social Affairs, 12 Ngo Quyen Str, Hoan Kiem District, Ha Noi 110905, Viet Nam.

Although the End TB Strategy highlights that major global progress towards universal health coverage (UHC) and social protection are fundamental to achieving the global targets for reductions in tuberculosis (TB) incidence and deaths, there is still a long way to go to achieve them in low- and middle-income countries. A workshop on the End TB Strategy Pillar 2 in the Western Pacific Region focusing on action towards UHC and social protection was held between 27 and 29 November in 2017 at the Korean Institute of Tuberculosis in Cheonju, Republic of Korea. The workshop brought together key personnel from national TB programmes and other stakeholders or researchers with experience in this topic from six countries with a high burden of TB in the region. During the workshop, participants shared country experiences, best practices, and challenges in achieving UHC and enhancing social protection in the context of TB service delivery, and also explored policy options to address the challenges, to be applied in their respective countries. This report describes the content of the meeting and the conclusions and recommendations arising from the meeting.
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http://dx.doi.org/10.3390/tropicalmed4010003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6473827PMC
December 2018

Comparison of DNA extraction methods for drug susceptibility testing by allele-specific primer extension on a microsphere-based platform: Chelex-100 (in-house and commercialized) and MagPurix TB DNA Extraction Kit.

J Microbiol Methods 2018 09 31;152:105-108. Epub 2018 Jul 31.

Korean Institute of Tuberculosis, 168-5 Osongsaengmyeong 4-ro, Osong-eup, Heungdeok-gu, Cheongju 28158, Republic of Korea. Electronic address:

Tuberculosis (TB), caused by infections of the Mycobacterium tuberculosis (MTB) complex, is the ninth leading cause of death worldwide, and several molecular approaches for MTB species identification and the detection of mutations associated with drug resistance have been developed to date. We previously developed a diagnostic assay for drug susceptibility testing that can detect mutations conferring resistance to anti-TB drugs using allele-specific primer extension on a microsphere-based platform for multiplex polymerase chain reaction. The aim of the present study was to optimize this diagnostic assay based on the evaluation of three methods for extracting mycobacterial DNA from clinical samples. Mycobacterial DNA of 81 samples was digested and decontaminated by N-acetyl-l-cysteine-2% NaOH and then extracted using three methods: "in-house" 5% Chelex-100 chelating resin, InstaGene Matrix, and MagPurix TB DNA Extraction Kit. The former two methods are manual extraction methods, whereas the MagPurix TB DNA Extraction Kit is an automated extraction method used with the MagPurix 12 s automated nucleic acid purification system. The extracted DNA was then subjected to our diagnostic assay, and the results were compared among methods. The magnetic bead method exhibited a higher extraction efficiency and resulted in greater diagnostic efficacy than the two resin-based methods with respect to both target gene detection and acid-fast bacilli smear grades. Therefore, the MagPurix TB DNA Extraction Kit is the optimal MTB DNA extraction method for our diagnostic assay of TB drug susceptibility testing.
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http://dx.doi.org/10.1016/j.mimet.2018.07.019DOI Listing
September 2018

A molecular epidemiological analysis of tuberculosis trends in South Korea.

Tuberculosis (Edinb) 2018 07 6;111:127-134. Epub 2018 Jun 6.

Seoul Clinical Laboratories, Yongin-si, Gyeonggi-do, Republic of Korea. Electronic address:

Molecular epidemiological data are needed to assess tuberculosis (TB)-management policy outcomes in South Korea. IS6110 restriction fragment-length polymorphism (IS6110-RFLP) and mycobacterial interspersed repetitive unit-variable-number tandem repeat (MIRU-VNTR) analyses are major molecular epidemiological tools for investigating the transmission or reactivation of active TB. Here, we determined trends in the clustering rate (i.e., the prevalence of Mycobacterium tuberculosis isolates with identical genotype patterns) of active TB and related differences between the 1990s and 2000s in Korea. M. tuberculosis isolates (1,007) of nationwide origins were analyzed by IS6110-RFLP and 24-locus standardized MIRU-VNTR genotyping. The clustering rate was measured by IS6110-RFLP, 24-locus MIRU-VNTR, and both analytical methods in combination. IS6110-RFLP, 24-locus MIRU-VNTR typing, and the combined method revealed 882, 754, and 983 distinct profiles; 809, 651, and 961 unique isolates; and 198, 356, and 46 clustered isolates grouped into 73, 103, and 22 clusters, respectively. In addition, we confirmed that the clustering rates in the 2000s decreased by 11.2%, 2.1%, and 3.1% relative to that in the 1990s using the three methods, respectively. Furthermore, in multivariate analysis, the younger-age group (<30) clustered more frequently than the older-age group (>50), based on all the three methods. Our study is the first report to provide nationwide molecular epidemiological information on TB in Korea.
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http://dx.doi.org/10.1016/j.tube.2018.06.003DOI Listing
July 2018

Delamanid, Bedaquiline, and Linezolid Minimum Inhibitory Concentration Distributions and Resistance-related Gene Mutations in Multidrug-resistant and Extensively Drug-resistant Tuberculosis in Korea.

Ann Lab Med 2018 Nov;38(6):563-568

Department of R&D, Korean Institute of Tuberculosis, Cheongju, Korea.

Background: Delamanid, bedaquiline, and linezolid have recently been approved for the treatment of multidrug- and extensively drug-resistant (MDR and XDR, respectively) tuberculosis (TB). To use these drugs effectively, drug susceptibility tests, including rapid molecular techniques, are required for accurate diagnosis and treatment. Furthermore, mutation analyses are needed to assess the potential for resistance. We evaluated the minimum inhibitory concentrations (MICs) of these three anti-TB drugs for Korean MDR and XDR clinical strains and mutations in genes related to resistance to these drugs.

Methods: MICs were determined for delamanid, bedaquiline, and linezolid using a microdilution method. The PCR products of drug resistance-related genes from 420 clinical Mycobacterium tuberculosis strains were sequenced and aligned to those of M. tuberculosis H37Rv.

Results: The overall MICs for delamanid, bedaquiline, and linezolid ranged from ≤0.025 to >1.6 mg/L, ≤0.0312 to >4 mg/L, and ≤0.125 to 1 mg/L, respectively. Numerous mutations were found in drug-susceptible and -resistant strains. We did not detect specific mutations associated with resistance to bedaquiline and linezolid. However, the Gly81Ser and Gly81Asp mutations were associated with resistance to delamanid.

Conclusions: We determined the MICs of three anti-TB drugs for Korean MDR and XDR strains and identified various mutations in resistance-related genes. Further studies are needed to determine the genetic mechanisms underlying resistance to these drugs.
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http://dx.doi.org/10.3343/alm.2018.38.6.563DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6056398PMC
November 2018

In Reply.

Int J Tuberc Lung Dis 2017 12;21(12):1314-1315

Korean Institute of Tuberculosis, Cheongju, Korea.

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http://dx.doi.org/10.5588/ijtld.17.0436-2DOI Listing
December 2017

Persisting positron emission tomography lesion activity and Mycobacterium tuberculosis mRNA after tuberculosis cure.

Nat Med 2016 10 5;22(10):1094-1100. Epub 2016 Sep 5.

National Medical Center, Seoul, South Korea.

The absence of a gold standard to determine when antibiotics induce a sterilizing cure has confounded the development of new approaches to treat pulmonary tuberculosis (PTB). We detected positron emission tomography and computerized tomography (PET-CT) imaging response patterns consistent with active disease, along with the presence of Mycobacterium tuberculosis (MTB) mRNA in sputum and bronchoalveolar lavage samples, in a substantial proportion of adult, HIV-negative patients with PTB after a standard 6-month treatment plus 1 year follow-up, including patients with a durable cure and others who later developed recurrent disease. The presence of MTB mRNA in the context of nonresolving and intensifying lesions on PET-CT images might indicate ongoing transcription, suggesting that even apparently curative treatment for PTB may not eradicate all of the MTB bacteria in most patients. This suggests an important complementary role for the immune response in maintaining a disease-free state. Sterilizing drugs or host-directed therapies, and better treatment response markers, are probably needed for the successful development of improved and shortened PTB-treatment strategies.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5053881PMC
http://dx.doi.org/10.1038/nm.4177DOI Listing
October 2016

Predictors of pulmonary tuberculosis treatment outcomes in South Korea: a prospective cohort study, 2005-2012.

BMC Infect Dis 2014 Jul 2;14:360. Epub 2014 Jul 2.

International Tuberculosis Research Center, Changwon, Republic of Korea.

Background: Tuberculosis remains an important health concern in many countries. The aim of this study was to identify predictors of unfavorable outcomes at the end of treatment (EOT) and at the end of study (EOS; 40 months after EOT) in South Korea.

Methods: New or previously treated tuberculosis patients were recruited into a prospective observational cohort study at two hospitals in South Korea. To identify predictors of unfavorable outcomes at EOT and EOS, logistic regression analysis was performed.

Results: The proportion of multidrug-resistant tuberculosis (MDR-TB) was 8.2% in new cases and 57.9% in previously treated cases. Of new cases, 68.6% were cured, as were 40.7% of previously treated cases. At EOT, diabetes, ≥3 previous TB episodes, ≥1 significant regimen change, and MDR-TB were significantly associated with treatment failure or death. At EOS, age ≥35, body-mass index (BMI) <18.5, diabetes, and MDR-TB were significantly associated with treatment failure, death, or relapse. Among cases that were cured at EOT, age ≥50 and a BMI <18.5 were associated with subsequent death or relapse during follow-up to EOS. Treatment interruption was associated with service sector employees or laborers, bilateral lesions on chest X-ray, and previous treatment failure or treatment interruption history.

Conclusions: Risk factors for poor treatment outcomes at EOT and EOS include both patient factors (diabetes status, age, BMI) and disease factors (history of multiple previous treatment episodes, MDR-TB). In this longitudinal, observational cohort study, diabetes mellitus and MDR-TB were risk factors for poor treatment outcomes and relapse. Measures to help ensure that the first tuberculosis treatment episode is also the last one may improve treatment outcomes.

Trial Registration: ClinicalTrials.gov ID: NCT00341601.
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http://dx.doi.org/10.1186/1471-2334-14-360DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4094632PMC
July 2014

Fitness costs of rifampicin resistance in Mycobacterium tuberculosis are amplified under conditions of nutrient starvation and compensated by mutation in the β' subunit of RNA polymerase.

Mol Microbiol 2014 Mar 26;91(6):1106-19. Epub 2014 Feb 26.

International Tuberculosis Research Center, Changwon, South Korea.

Rifampicin resistance, a defining attribute of multidrug-resistant tuberculosis, is conferred by mutations in the β subunit of RNA polymerase. Sequencing of rifampicin-resistant (RIF-R) clinical isolates of Mycobacterium tuberculosis revealed, in addition to RIF-R mutations, enrichment of potential compensatory mutations around the double-psi β-barrel domain of the β' subunit comprising the catalytic site and the exit tunnel for newly synthesized RNA. Sequential introduction of the resistance allele followed by the compensatory allele in isogenic Mycobacterium smegmatis showed that these mutations respectively caused and compensated a starvation enhanced growth defect by altering RNA polymerase activity. While specific combinations of resistance and compensatory alleles converged in divergent lineages, other combinations recurred among related isolates suggesting transmission of compensated RIF-R strains. These findings suggest nutrient poor growth conditions impose larger selective pressure on RIF-R organisms that results in the selection of compensatory mutations in a domain involved in catalysis and starvation control of RNA polymerase transcription.
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http://dx.doi.org/10.1111/mmi.12520DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3951610PMC
March 2014

Impact of diabetes and smoking on mortality in tuberculosis.

PLoS One 2013 28;8(2):e58044. Epub 2013 Feb 28.

Department of Preventive and Behavioral Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America.

Background: Diabetes mellitus is a risk factor for tuberculosis (TB) disease. There is evidence that diabetes also influences TB severity and treatment outcomes but information is incomplete and some published results have been inconsistent.

Methods: A longitudinal cohort study was conducted at the National Masan Tuberculosis Hospital in the Republic of Korea. Subjects presenting with a first episode of TB or for retreatment of TB were followed from enrollment through completion of treatment. Demographic, clinical, and microbiological variables were recorded, along with assessment of outcomes. Results were compared in TB patients with and without diabetes or smoking history. Data were adjusted for gender, age, cohort, educational level and alcohol consumption.

Results: The combined cohorts comprised 657 subjects. Diabetes was present in 25% and was associated with greater radiographic severity and with recurrent or relapsed TB. Diabetes and cigarette smoking independently increased the risk of death in the first 12 months after enrollment. Estimating the combined impact of diabetes and smoking yielded a hazard ratio of 5.78. Only 20% of diabetic subjects were non-smokers; 54% smoked ≥1 pack daily. In this cohort, the impact of diabetes on mortality was greater in patients younger than 50 years, compared to older patients.

Conclusions: In this cohort of Korean patients, diabetes exacerbated the severity of TB disease. Diabetic subjects who smoked ≥1 pack of cigarettes daily were at particularly high risk of death from TB. Strategies to improve TB outcomes could productively focus resources for patient education and TB prevention on the vulnerable population of younger diabetics, particularly those who also smoke.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0058044PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3585219PMC
August 2013

Proportion of multidrug-resistant tuberculosis in human immunodeficiency virus/mycobacterium tuberculosis co-infected patients in Korea.

J Korean Med Sci 2012 Oct 2;27(10):1143-6. Epub 2012 Oct 2.

Department of Internal Medicine, National Medical Center, Seoul, Korea.

Much controversy surrounds the issue of whether HIV infection is a risk factor for developing multidrug-resistant tuberculosis (MDR-TB). In this study, we evaluated the prevalence of and risk factors for MDR-TB in HIV-infected patients at the National Medical Center of Korea. We reviewed the medical records of HIV/TB co-infected patients from January 2005 to May 2011; the drug susceptibility profiles were available for 55 patients. Of these, 32.7% had MDR-TB, which was approximately 3.6 times higher than the prevalence among the general population. Additionally, there were more additional AIDS-defining clinical illnesses in the MDR-TB group than in the non-MDR-TB group (27.8% vs 5.4%, P = 0.032). These results suggest that HIV infection and HIV-related immunosuppresion may contribute to the development of MDR-TB.
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http://dx.doi.org/10.3346/jkms.2012.27.10.1143DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3468748PMC
October 2012

Linezolid for treatment of chronic extensively drug-resistant tuberculosis.

N Engl J Med 2012 Oct;367(16):1508-18

International Tuberculosis Research Center, Changwon, South Korea.

Background: Linezolid has antimycobacterial activity in vitro and is increasingly used for patients with highly drug-resistant tuberculosis.

Methods: We enrolled 41 patients who had sputum-culture-positive extensively drug-resistant (XDR) tuberculosis and who had not had a response to any available chemotherapeutic option during the previous 6 months. Patients were randomly assigned to linezolid therapy that started immediately or after 2 months, at a dose of 600 mg per day, without a change in their background regimen. The primary end point was the time to sputum-culture conversion on solid medium, with data censored 4 months after study entry. After confirmed sputum-smear conversion or 4 months (whichever came first), patients underwent a second randomization to continued linezolid therapy at a dose of 600 mg per day or 300 mg per day for at least an additional 18 months, with careful toxicity monitoring.

Results: By 4 months, 15 of the 19 patients (79%) in the immediate-start group and 7 of the 20 (35%) in the delayed-start group had culture conversion (P=0.001). Most patients (34 of 39 [87%]) had a negative sputum culture within 6 months after linezolid had been added to their drug regimen. Of the 38 patients with exposure to linezolid, 31 (82%) had clinically significant adverse events that were possibly or probably related to linezolid, including 3 patients who discontinued therapy. Patients who received 300 mg per day after the second randomization had fewer adverse events than those who continued taking 600 mg per day. Thirteen patients completed therapy and have not had a relapse. Four cases of acquired resistance to linezolid have been observed.

Conclusions: Linezolid is effective at achieving culture conversion among patients with treatment-refractory XDR pulmonary tuberculosis, but patients must be monitored carefully for adverse events. (Funded by the National Institute of Allergy and Infectious Diseases and the Ministry of Health and Welfare, South Korea; ClinicalTrials.gov number, NCT00727844.).
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http://dx.doi.org/10.1056/NEJMoa1201964DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3814175PMC
October 2012

Rhabdomyolysis in a patient treated with linezolid for extensively drug-resistant tuberculosis.

Clin Infect Dis 2012 Jun 15;54(11):1624-7. Epub 2012 Mar 15.

Tuberculosis Research Section, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, Maryland, USA.

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http://dx.doi.org/10.1093/cid/cis293DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3404720PMC
June 2012
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