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Fulltext Genomic epidemiology of tuberculosis in eastern Malaysia: insights for strengthening public health responses

Bainomugisa A, Meumann EM, Rajahram GS, Ong RT, Coin L, Paul DC, et al.

Microb Genom, 2021 05;7(5).
PMID: 33945455 DOI: 10.1099/mgen.0.000573

Tuberculosis is a leading public health priority in eastern Malaysia. Knowledge of the genomic epidemiology of tuberculosis can help tailor public health interventions. Our aims were to determine tuberculosis genomic epidemiology and characterize resistance mutations in the ethnically diverse city of Kota Kinabalu, Sabah, located at the nexus of Malaysia, Indonesia, Philippines and Brunei. We used an archive of prospectively collected Mycobacterium tuberculosis samples paired with epidemiological data. We collected sputum and demographic data from consecutive consenting outpatients with pulmonary tuberculosis at the largest tuberculosis clinic from 2012 to 2014, and selected samples from tuberculosis inpatients from the tertiary referral centre during 2012-2014 and 2016-2017. Two hundred and eight M. tuberculosis sequences were available for analysis, representing 8 % of cases notified during the study periods. Whole-genome phylogenetic analysis demonstrated that most strains were lineage 1 (195/208, 93.8 %), with the remainder being lineages 2 (8/208, 3.8 %) or 4 (5/208, 2.4 %). Lineages or sub-lineages were not associated with patient ethnicity. The lineage 1 strains were diverse, with sub-lineage 1.2.1 being dominant (192, 98 %). Lineage 1.2.1.3 isolates were geographically most widely distributed. The greatest diversity occurred in a border town sub-district. The time to the most recent common ancestor for the three major lineage 1.2.1 clades was estimated to be the year 1966 (95 % HPD 1948-1976). An association was found between failure of culture conversion by week 8 of treatment and infection with lineage 2 (4/6, 67 %) compared with lineage 1 strains (4/83, 5 %) (P<0.001), supporting evidence of greater virulence of lineage 2 strains. Eleven potential transmission clusters (SNP difference ≤12) were identified; at least five included people living in different sub-districts. Some linked cases spanned the whole 4-year study period. One cluster involved a multidrug-resistant tuberculosis strain matching a drug-susceptible strain from 3 years earlier. Drug resistance mutations were uncommon, but revealed one phenotype-genotype mismatch in a genotypically multidrug-resistant isolate, and rare nonsense mutations within the katG gene in two isolates. Consistent with the regionally mobile population, M. tuberculosis strains in Kota Kinabalu were diverse, although several lineage 1 strains dominated and were locally well established. Transmission clusters - uncommonly identified, likely attributable to incomplete sampling - showed clustering occurring across the community, not confined to households or sub-districts. The findings indicate that public health priorities should include active case finding and early institution of tuberculosis management in mobile populations, while there is a need to upscale effective contact investigation beyond households to include other contacts within social networks.

Matched MeSH terms: Tuberculosis, Pulmonary/epidemiology
Fulltext Effect of smoking on treatment outcome among tuberculosis patients in Malaysia; a multicenter study

Khan AH, Sulaiman SAS, Hassali MA, Khan KU, Ming LC, Mateen O, et al.

BMC Public Health, 2020 Jun 04;20(1):854.
PMID: 32498682 DOI: 10.1186/s12889-020-08856-6

BACKGROUND: Smoking plays a key role in the development of tuberculosis (TB) infection and is also a predictor of poor TB treatment prognosis and outcomes. The current study was conducted to determine the prevalence of smoking and to assess the effects of smoking on treatment outcomes among TB patients.
METHODS: A multi-center retrospective study design was used to collect data from TB patients in four different states of Malaysia, namely Penang, Sabah, Sarawak, and Selangor. The study included medical records of TB patients admitted to the selected hospitals in the period from January 2006 to March 2009. Medical records with incomplete data were not included. Patient demographics and clinical data were collected using a validated data collection form.
RESULTS: Of all patients with TB (9337), the prevalence of smokers was 4313 (46.2%). Among smokers, 3584 (83.1%) were associated with pulmonary TB, while 729 (16.9%) were associated with extrapulmonary TB. Male gender (OR = 1.43, 95% CI 1.30-1.58), Chinese ethnicity (OR = 1.23, 95% CI 1.02-1.49), Sarawak indigenous ethnicity (OR = 0.74, 95% CI 0.58-0.95), urban residents (OR = 1.46, 95% CI 1.33-1.61), employed individuals (OR = 1.21, 95% CI 1.09-1.34), alcoholics (OR = 4.91, 95% CI 4.04-5.96), drug abusers (OR = 7.43, 95% CI 5.70-9.60) and presence of co-morbid condition (OR = 1.27, 95% CI 1.16-1.40) all showed significant association with smoking habits. This study found that 3236 (75.0%) patients were successfully treated in the smokers' group, while 4004 (79.7%) patients were non-smokers. The proportion of deaths (6.6%, n = 283), defaulters (6.6%, n = 284) and treatment interruptions (4.7%, n = 204) was higher in the smokers' group.
CONCLUSIONS: Smoking has a strong influence on TB and is a major barrier towards treatment success (OR = 0.76, 95% CI 0.69-0.84, p

Matched MeSH terms: Tuberculosis, Pulmonary/epidemiology
Fulltext Costs associated with tuberculosis diagnosis and treatment in Yemen for patients and public health services

Othman GQ, Ibrahim MI, Raja'a YA

East Mediterr Health J, 2012 Apr;18(4):393-8.
PMID: 22768704

This study determined the costs associated with tuberculosis (TB) diagnosis and treatment for the public health services and patients in Sana'a, Yemen. Data were collected prospectively from 320 pulmonary and extrapulmonary TB patients (160 each) who were followed until completion of treatment. Direct medical and nonmedical costs and indirect costs were calculated. The proportionate cost to the patients for pulmonary TB and extrapulmonary TB was 76.1% arid 89.4% respectively of the total for treatment. The mean cost to patients for pulmonary and extrapulmonary TB treatment was US$ 108.4 and US$ 328.0 respectively. The mean cost per patient to the health services for pulmonary and extrapulmonary TB treatment was US$ 34.0 and US$ 38.8 respectively. For pulmonary and extrapulmonary TB, drug treatment represented 59.3% and 77.9% respectively of the total cost to the health services. The greatest proportionate cost to patients for pulmonary TB treatment was time away from work (67.5% of the total cost), and for extrapulmonary TB was laboratory and X-ray costs (55.5%) followed by transportation (28.6%).

Matched MeSH terms: Tuberculosis, Pulmonary/epidemiology
Fulltext Diagnostic delay among pulmonary tuberculosis patients in Sarawak, Malaysia: a cross-sectional study

Chang CT, Esterman A

Rural Remote Health, 2007 Apr-Jun;7(2):667.
PMID: 17511524

Delayed diagnosis of tuberculosis (TB) can lead to an increased period of infectivity in the community, a delay in treatment and a severe form of the disease. The objective of this study was to determine the length of delay, and factors linking the delay from the onset of symptoms of pulmonary tuberculosis (PTB) until the commencement of treatment in Sarawak, Malaysia.

Matched MeSH terms: Tuberculosis, Pulmonary/epidemiology*
Fulltext Tuberculosis in diabetic patients: a clinical perspective

Nissapatorn V, Kuppusamy I, Jamaiah I, Fong MY, Rohela M, Anuar AK

Southeast Asian J. Trop. Med. Public Health, 2005;36 Suppl 4:213-20.
PMID: 16438212

This retrospective and descriptive study was a report on the clinical situation of tuberculosis in diabetic patients, with 1,651 patients recruited. The mean age of TBDM patients was significantly higher than that of non-diabetic patients (p<0.05). Moreover, TBDM patients had a higher ratio of male to female than the other group. The significant proportion of TB appeared to increase steadily with age in diabetic patients compared to non-diabetic ones (p<0.05). However, they showed similarities in terms of sex, race, marital status, present address, and occupation. A higher percentage of pulmonary tuberculosis (91.4%) was shown in the TBDM group. We found that both groups had no differences in the radiological findings, with opacity or cavity of the upper lobe involvement being 89% and 91% in TBDM and non-diabetic groups, respectively. TBDM patients were shown to have more treatment success (33.3%), particularly the pulmonary type of tuberculosis in the longer duration ( 9 months). Further findings demonstrated that a lower proportion of the TBDM group defaulted in their treatment (19.8%) and experienced resistance to anti-tubercular therapy (1.4%) compared to non-diabetics.

Matched MeSH terms: Tuberculosis, Pulmonary/epidemiology
Fulltext Diabetes mellitus and its influence on sputum smear positivity at the 2nd month of treatment among pulmonary tuberculosis patients in Kuala Lumpur, Malaysia: A case control study

Shariff NM, Safian N

Int J Mycobacteriol, 2015 Dec;4(4):323-9.
PMID: 26964816 DOI: 10.1016/j.ijmyco.2015.09.003

OBJECTIVE/BACKGROUND: Many studies have suggested that sputum smear conversion after 2 months of antituberculosis treatment is an important determinant of treatment success and can be a predictor for relapse. The objective of this study is to determine the factors that influence sputum smear conversion after 2 months of treatment among pulmonary tuberculosis patients receiving treatment in the Institute of Respiratory Medicine in Kuala Lumpur, Malaysia.
METHODS: A total of 75 cases and 75 controls were interviewed, and their medical records were retrieved in order to extract the information needed. All analyses were conducted using SPSS version 17, and binary logistic regression analysis was used to determine the predictors of sputum smear nonconversion.
RESULTS: Results showed that the following factors were associated with sputum smear positivity after 2 months of intensive treatment: diabetes mellitus (p=.013, odds ratio [OR]=2.59, 95% confidence interval [CI] 1.27-5.33), underweight body mass index (p=.025, OR=1.67, 95% CI 0.80-3.49), nonadherent to tuberculosis treatment (p=.024, OR=2.85, 95% CI 1.21-6.74), and previous history of tuberculosis (p=.043, OR=2.53, 95% CI 1.09-5.83). Multivariable analysis identified diabetes mellitus (p=.003, OR=4.01, 95% CI 1.61-9.96) as being independently associated with the risk of persistent sputum smear positivity after 2 months of intensive treatment.
CONCLUSION: Based on the findings, identification of these factors is valuable in strengthening the management and treatment of tuberculosis in Malaysia in the future. This study emphasizes the importance of diabetes screening and integration of diabetic controls among tuberculosis patients in achieving better treatment outcome.
KEYWORDS: Risk factors; Sputum smear nonconversion; Tuberculosis

Matched MeSH terms: Tuberculosis, Pulmonary/epidemiology
Tuberculosis: clinical manifestations and outcomes

Nissapatorn V, Kuppusamy I, Anuar AK, Quek KF, Latt HM

Southeast Asian J. Trop. Med. Public Health, 2003;34 Suppl 2:147-52.
PMID: 19238668

A total of 290 HIV/AIDS patients were recruited into this retrospective study, which was carried out at the National Tuberculosis Center (NTBC), Kuala Lumpur. The age range was 18 to 75 years with a mean age of 36.10 (SD +/- 7.44) years. Males outnumbered females by a ratio of 31:1. In this study, the majority of patients were male (96.9%), Malay (47.2%), single (66.9%), unemployed (81%), and smoked (61.4%). The main risk marker identified was injecting drug use (74.5%). The most common clinical manifestations were cough, fever, sputum, lymphadenopathy, and chest infiltrations. More than half of the patients (85.9%) were diagnosed with localized tuberculosis (pulmonary) and the others (14.1%) had extra-pulmonary or disseminated tuberculosis. At the time of this study, the majority of the patients (16.9%) had CD4 cell counts of less than 200 cell/mm3, with a median of 221 cell/mm3. Clinical outcomes demonstrated that among those who survived, 11.0% and 20.7% of the patients had completed treatment either > or = 6 or > or = 9 months, respectively, whereas 54.8% of patients were lost to follow-up, including 0.7% for MDR-TB. Diagnostic criteria for tuberculosis in this study were mainly clinical symptoms/signs and chest x-ray findings (31.0%).

Matched MeSH terms: Tuberculosis, Pulmonary/epidemiology
Delay in the diagnosis and treatment of pulmonary tuberculosis in patients attending a university teaching hospital

Liam CK, Tang BG

Int J Tuberc Lung Dis, 1997 Aug;1(4):326-32.
PMID: 9432388

University Hospital, Kuala Lumpur, Malaysia.

Matched MeSH terms: Tuberculosis, Pulmonary/epidemiology
Fulltext Treatment outcomes and risk factors of extra-pulmonary tuberculosis in patients with co-morbidities

Khan AH, Sulaiman SAS, Laghari M, Hassali MA, Muttalif AR, Bhatti Z, et al.

BMC Infect Dis, 2019 Aug 05;19(1):691.
PMID: 31382889 DOI: 10.1186/s12879-019-4312-9

BACKGROUND: Extra-pulmonary tuberculosis (EPTB) represents about 14% of all cases of tuberculosis (TB) in Malaysia. The aims of the study include evaluation of socio-demographic factors, clinical manifestations, co-morbidities among patients with EPTB and their treatment outcomes.
METHODS: A retrospective study was conducted to recognize the epidemiology facts of EPTB. Individual data for EPTB patients were collected from TB registers, laboratory TB registers, treatment cards and TB medical personal files into a standardized study questionnaire. Crude (COR) and adjusted odds ratios (AOR) and 95% confidence intervals (CI) were determined to assess the risk factors for EPTB and unsuccessful treatment outcomes.
RESULTS: There were 1222 EPTB patients presenting 13.1% of all TB cases during 2006-2008. Pleural effusion and lymph node TB were the most frequent types and accounted for 45.1% of all EPTB cases among study participants. Treatment success rate was 67.6%. The best treatment completion rates were found in children ≤15 years (0.478 [0.231-1.028]; p = 0.05). On multivariate analysis, age group 56-65 years (1.658 [1.157-2.376]; p = 0.006), relapse cases (7.078 [1.585-31.613]; p = 0.010), EPTB-DM (1.773 [1.165-2.698]; p = 0.008), patients with no formal (2.266 [1.254-4.095]; p = 0.001) and secondary level of education (1.889 [1.085-3.288]; p = 0.025) were recorded as statistically positive significant risk factors for unsuccessful treatment outcomes. Patients at the risk of EPTB were more likely to be females (1.524 [1.311-1.746]; p

Matched MeSH terms: Tuberculosis, Pulmonary/epidemiology
Fulltext AIDS-related opportunistic infections in Hospital Kuala Lumpur

Nissapatorn V, Lee C, Quek KF, Abdullah KA

Jpn J Infect Dis, 2003 Oct-Dec;56(5-6):187-92.
PMID: 14695428

We retrospectively reviewed 419 HIV/AIDS patients in Hospital Kuala Lumpur from 1994 to 2001. In the male group, the age range was 20-74, with a mean age 37 years, while in the female group it was 17-63, with a mean age of 33 years. With regard to age group, it was found that the preponderant age group was 25-34 years. The majority of male subjects were Chinese (52.5%), single (56.3%), and unemployed (55.1%), whereas the females were Malay (42.3%), married (79.5%), and non-laborer (64.1%). Also, both groups resided in Kuala Lumpur and had heterosexual contact as the leading cause of HIV transmission. More than half of the patients had CD4 cell counts of <200 cells/cumm. We found that the acquisition of HIV infection via intravenous drug use (IDU) was directly related to the incidence of tuberculosis infection (P < 0.05). Further analysis showed HIV-related tuberculosis with IDU was also dependently correlated with occupational status (unemployed) (P < 0.05). The four main AIDS-defining diseases include tuberculosis (48%), Pneumocystis carinii pneumonia (13%), toxoplasmic encephalitis (11%), and cryptococcal meningitis (7%); in addition, 53% of these patients were found to have CD4 cell counts of less than 200 cells/cumm at the time of diagnosis.

Matched MeSH terms: Tuberculosis, Pulmonary/epidemiology
Fulltext Pulmonary tuberculosis in outpatients in Sabah, Malaysia: advanced disease but low incidence of HIV co-infection

William T, Parameswaran U, Lee WK, Yeo TW, Anstey NM, Ralph AP

BMC Infect Dis, 2015;15:32.
PMID: 25636334 DOI: 10.1186/s12879-015-0758-6

BACKGROUND: Tuberculosis (TB) is generally well controlled in Malaysia, but remains an important problem in the nation's eastern states. In order to better understand factors contributing to high TB rates in the eastern state of Sabah, our aims were to describe characteristics of patients with TB at a large outpatient clinic, and determine the prevalence of HIV co-infection. Additionally, we sought to test sensitivity and specificity of the locally-available point-of-care HIV test kits.
METHODS: We enrolled consenting adults with smear-positive pulmonary TB for a 2-year period at Luyang Clinic, Kota Kinabalu, Malaysia. Participants were questioned about ethnicity, smoking, prior TB, disease duration, symptoms and comorbidities. Chest radiographs were scored using a previously devised tool. HIV was tested after counselling using 2 point-of-care tests for each patient: the test routinely in use at the TB clinic (either Advanced Quality™ Rapid Anti-HIV 1&2, FACTS anti-HIV 1/2 RAPID or HIV (1 + 2) Antibody Colloidal Gold), and a comparator test (Abbott Determine™ HIV-1/2, Inverness Medical). Positive tests were confirmed by enzyme immunoassay (EIA), particle agglutination and line immunoassay.
RESULTS: 176 participants were enrolled; 59 (33.5%) were non-Malaysians and 104 (59.1%) were male. Smoking rates were high (81/104 males, 77.9%), most had cavitary disease (51/145, 64.8%), and 81/176 (46.0%) had haemoptysis. The median period of symptoms prior to treatment onset was 8 weeks. Diabetes was present in 12. People with diabetes or other comorbidities had less severe TB, suggesting different healthcare seeking behaviours in this group. All participants consented to HIV testing: three (1.7%) were positive according to Determine™ and EIA, but one of these tested negative on the point-of-care test available at the clinic (Advanced Quality™ Rapid Anti-HIV 1&2). The low number of positive tests and changes in locally-available test type meant that accurate estimates of sensitivity and specificity were not possible.
CONCLUSION: Patients had advanced disease at diagnosis, long diagnostic delays, low HIV co-infection rates, high smoking rates among males, and migrants may be over-represented. These findings provide important insights to guide local TB control efforts. Caution is required in using some point-of-care HIV tests, and ongoing quality control measures are of major importance.
Study site: Klinik Kesihatan Luyang (Tuberculosis Clinic), Kota Kinabalu, Sabah, Malaysia,

Matched MeSH terms: Tuberculosis, Pulmonary/epidemiology*
The reliability of a rapid molecular detection method in determining the prevalence of rifampicin-resistant Mycobacterium tuberculosis in an urban district health facility in Malaysia

Ding CH, Ismail Z, Sulong A, Wahab AA, Gan B, Mustakim S, et al.

Malays J Pathol, 2020 Dec;42(3):401-407.
PMID: 33361721

INTRODUCTION: Rifampicin is a key first-line antimycobacterial agent employed for the treatment of pulmonary tuberculosis (PTB). This study sought to obtain prevalence data on rifampicin-resistant Mycobacterium tuberculosis among smear-positive PTB patients in the Klang District of Malaysia.
MATERIALS AND METHODS: A total of 103 patients from the Chest Clinic of Hospital Tengku Ampuan Rahimah with sputum smears positive for acid-fast bacilli were included in this cross-sectional study. All sputa were tested using Xpert MTB/RIF to confirm the presence of M. tuberculosis complex and detect rifampicin resistance. Sputa were also sent to a respiratory medicine institute for mycobacterial culture. Positive cultures were then submitted to a reference laboratory, where isolates identified as M. tuberculosis complex underwent drug susceptibility testing (DST).
RESULTS: A total of 58 (56.3%) patients were newly diagnosed and 45 (43.7%) patients were previously treated. Xpert MTB/RIF was able to detect rifampicin resistance with a sensitivity and specificity of 87.5% and 98.9%, respectively. Assuming that a single resistant result from Xpert MTB/RIF or any DST method was sufficient to denote resistance, a total of 8/103 patients had rifampicinresistant M. tuberculosis. All eight patients were previously treated for PTB (p<0.05). The overall prevalence of rifampicin resistance among smear-positive PTB patients was 7.8%, although it was 17.8% among the previously treated ones.
CONCLUSION: The local prevalence of rifampicin-resistant M. tuberculosis was particularly high among previously treated patients. Xpert MTB/RIF can be employed in urban district health facilities not only to diagnose PTB in smear-positive patients, but also to detect rifampicin resistance with good sensitivity and specificity.

Matched MeSH terms: Tuberculosis, Pulmonary/epidemiology
Pulmonary tuberculosis presenting as community-acquired pneumonia

Liam CK, Pang YK, Poosparajah S

Respirology, 2006 Nov;11(6):786-92.
PMID: 17052309

The aims of this study were to investigate the frequency of Mycobacterium tuberculosis as a cause of community-acquired pneumonia (CAP) requiring hospitalization in Malaysia, and to define the clinical features of pulmonary tuberculosis (PTB) that distinguish it from non-TB CAP.

Matched MeSH terms: Tuberculosis, Pulmonary/epidemiology
Characteristics of HIV-infected tuberculosis patients in Kota Bharu Hospital, Kelantan from 1998 to 2001

Mohammad Z, Naing NN

Southeast Asian J. Trop. Med. Public Health, 2004 Mar;35(1):140-3.
PMID: 15272757

To characterize the demographic profiles, clinical features, radiological patterns and outcomes of treatment of HIV-infected TB patients, a descriptive study was carried out on 149 HIV-infected TB cases diagnosed from 1998 through 2001 at Kota Bharu Hospital, Kelantan, Malaysia. The majority of the patients were males (94.6%), single (45.0%), ethnic Malay (94.0%) with a mean age of 34 years (standard deviation 7.8, range 18-76). The most common HIV transmission category was through injecting drug use (73.8%) and being the inmates or former inhabitants of drug rehabilitation centers and prisons were the commonest high-risk groups. One hundred and seventeen patients were diagnosed as having pulmonary TB, while about 20% were extra-pulmonary in type with 9 cases of milliary TB. The majority (45%) presented with cough symptoms while only 51% had a positive sputum smear. Fifty-five percent were found to have pulmonary lesions on chest x-ray, such as localized, milliary or diffuse pulmonary infiltrates, or opacities. Eight (5.4%) had pleural lesions while another 8 cases had hilar or mediastinal lymph node lesions. Overall, fifty-eight (38.9%) patients had died by the completion of data collection. The median weeks or survival from the time of starting TB treatment was 13.5 (range 1-56) and the majority of them (74%) died without completing the 6-month regime of treatment.

Matched MeSH terms: Tuberculosis, Pulmonary/epidemiology*
Building a tuberculosis-free world: The Lancet Commission on tuberculosis

Reid MJA, Arinaminpathy N, Bloom A, Bloom BR, Boehme C, Chaisson R, et al.

Lancet, 2019 Mar 30;393(10178):1331-1384.
PMID: 30904263 DOI: 10.1016/S0140-6736(19)30024-8
Matched MeSH terms: Tuberculosis, Pulmonary/epidemiology
Pattern of first- and second-line drug resistance among pulmonary tuberculosis retreatment cases in Pakistan

Javaid A, Hasan R, Zafar A, Chaudry MA, Qayyum S, Qadeer E, et al.

Int J Tuberc Lung Dis, 2017 03 01;21(3):303-308.
PMID: 28225340 DOI: 10.5588/ijtld.16.0444

BACKGROUND: Drug resistance in general, and multidrug-resistant tuberculosis (MDR-TB) in particular, threatens global tuberculosis (TB) control efforts. Population-based estimates of drug resistance are needed to develop strategies for controlling drug-resistant TB in Pakistan.
OBJECTIVE: To obtain population-based data on Mycobacterium tuberculosis drug resistance in Pakistan.
METHODS: To obtain drug resistance data, we conducted a population-based study of TB cases in all provinces of Pakistan. We performed culture and drug susceptibility testing on M. tuberculosis isolates from patients with a prior history of anti-tuberculosis treatment (retreatment cases) from all over the country.
RESULTS: Of 544 isolates from previously treated cases, 289 (53.1%) were susceptible to all first-line drugs, 255 (46.9%) were resistant to at least one anti-tuberculosis drug and 132 (24.3%) were MDR-TB. Among MDR-TB isolates, 47.0% were ofloxacin (OFX) resistant. Extensively drug-resistant TB was found in two (0.4%) isolates.
CONCLUSION: Prevalence of drug resistance in retreatment isolates was high. The alarmingly high prevalence of OFX resistance among MDR-TB isolates may threaten the success of efforts to control and treat MDR-TB.

Matched MeSH terms: Tuberculosis, Pulmonary/epidemiology

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