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      Prevalence and associated factors of delayed sputum smear conversion in patients treated for smear positive pulmonary tuberculosis: A retrospective follow up study in Sabah, Malaysia

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          Abstract

          Introduction

          Tuberculosis remains a major health problem globally and in Malaysia, particularly in the state of Sabah. Delayed sputum conversion is associated with treatment failure, drug-resistant tuberculosis and mortality. We aimed to determine the prevalence of delayed sputum conversion among smear positive pulmonary tuberculosis (PTB) patients and its associated factors in Sabah, Malaysia.

          Methods

          A retrospective follow up study on all patients newly diagnosed with smear positive pulmonary tuberculosis from 2017 to 2019 was conducted at three government health clinics in Sabah, utilizing data from a national electronic tuberculosis database and medical records. Descriptive statistics and binary logistic regression were applied for data analysis. The outcome of the study was the sputum conversion status at the end of the two-month intensive treatment phase with either successful conversion to smear negative or non-conversion.

          Results

          374 patients were included in the analysis. Our patients were generally younger than 60 years old with no medical illness and varying proportions of tuberculosis severity as judged by radiographic appearance and sputum bacillary load upon diagnosis. Foreigners constituted 27.8% of our sample. 8.8% (confidence interval: 6.2–12.2) did not convert to smear negative at the end of the intensive phase. Binary logistic regression showed that older patients ≥60 years old (adjusted odds ratio, AOR = 4.303), foreigners (AOR = 3.184) and patients with higher sputum bacillary load at diagnosis [2+ (AOR = 5.061) and 3+ (AOR = 4.992)] were more likely to have delayed sputum smear conversion.

          Conclusion

          The prevalence of delayed sputum conversion in our study was considerably low at 8.8% with age ≥60 years old, foreigners and higher pre-treatment sputum bacillary load associated with delayed conversion. Healthcare providers should take note of these factors and ensure the patients receive proper follow up treatment.

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          Most cited references39

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          Model building strategy for logistic regression: purposeful selection.

          Logistic regression is one of the most commonly used models to account for confounders in medical literature. The article introduces how to perform purposeful selection model building strategy with R. I stress on the use of likelihood ratio test to see whether deleting a variable will have significant impact on model fit. A deleted variable should also be checked for whether it is an important adjustment of remaining covariates. Interaction should be checked to disentangle complex relationship between covariates and their synergistic effect on response variable. Model should be checked for the goodness-of-fit (GOF). In other words, how the fitted model reflects the real data. Hosmer-Lemeshow GOF test is the most widely used for logistic regression model.
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            Influence of diabetes on manifestations and treatment outcome of pulmonary TB patients.

            To understand the influence of diabetes on the clinical and bacteriological aspects and treatment outcome of pulmonary tuberculosis (PTB) patients. Records of 692 consecutive smear-positive PTB patients admitted to a referral hospital in Riyadh, Saudi Arabia, were reviewed retrospectively. The characteristics of 187 patients with diabetes mellitus (PTB-DM group) were compared to 505 patients without DM (PTB group). In the PTB-DM group, 65.2% of the patients had numerous acid-fast bacilli (AFB) on sputum smear examination compared to 54.1% in the control group (P = 0.008). Among new cases, PTB-DM patients had a lower prevalence of resistance to any anti-tuberculosis drug (6.4% vs. 16.0%, P = 0.007) and achieved higher sputum conversion rates at the end of 3 months of treatment (98.9% vs. 94.7%, P = 0.013). Favourable outcomes (cured/treatment completed), failure, death and default were comparable in both groups (P = 0.7005). PTB-DM patients have a higher pre-treatment bacillary load, a lower prevalence of anti-tuberculosis drug resistance and achieve slightly higher sputum conversion by the end of 3 months of treatment compared to non-diabetic patients. The association of diabetes does not alter the final treatment outcome among PTB patients.
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              Molecular Bacterial Load Assay, a Culture-Free Biomarker for Rapid and Accurate Quantification of Sputum Mycobacterium tuberculosis Bacillary Load during Treatment

              A molecular assay to quantify Mycobacterium tuberculosis is described. In vitro , 98% ( n = 96) of sputum samples with a known number of bacilli (10 7 to 10 2 bacilli) could be enumerated within 0.5 log 10 . In comparison to culture, the molecular bacterial load (MBL) assay is unaffected by other microorganisms present in the sample, results are obtained more quickly (within 24 h) and are seldom inhibited (0.7% samples), and the MBL assay critically shows the same biphasic decline as observed longitudinally during treatment. As a biomarker of treatment response, the MBL assay responds rapidly, with a mean decline in bacterial load for 111 subjects of 0.99 log 10 (95% confidence interval [95% CI], 0.81 to 1.17) after 3 days of chemotherapy. There was a significant association between the rate of bacterial decline during the same 3 days and bacilli ml −1 sputum at day 0 (linear regression, P = 0.0003) and a 3.62 increased odds ratio of relapse for every 1 log 10 increase in pretreatment bacterial load (95% CI, 1.53 to 8.59).
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: Project administrationRole: ResourcesRole: SoftwareRole: Writing – original draft
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: Project administrationRole: ResourcesRole: SoftwareRole: Writing – original draft
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: Project administrationRole: ResourcesRole: SoftwareRole: Writing – original draft
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: Project administrationRole: ResourcesRole: SoftwareRole: Writing – original draft
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: Project administrationRole: ResourcesRole: SoftwareRole: Writing – original draft
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: Project administrationRole: ResourcesRole: SoftwareRole: Writing – original draft
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: SupervisionRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: ResourcesRole: SoftwareRole: SupervisionRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS One
                plos
                PLOS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                6 March 2023
                2023
                : 18
                : 3
                : e0282733
                Affiliations
                [1 ] Luyang Health Clinic, Kota Kinabalu, Sabah, Malaysia
                [2 ] Tamparuli Health Clinic, Tuaran, Sabah, Malaysia
                [3 ] Penampang Health Clinic, Penampang, Sabah, Malaysia
                [4 ] Permai Polyclinic Sri Kepayan, Kota Kinabalu, Sabah, Malaysia
                [5 ] Department of Primary Care Medicine, Faculty of Medicine, Universiti Malaya, Kuala Lumpur, Malaysia
                [6 ] Department of Family Medicine, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Selangor, Malaysia
                The University of Georgia, UNITED STATES
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Author information
                https://orcid.org/0000-0002-3074-9114
                Article
                PONE-D-22-24926
                10.1371/journal.pone.0282733
                9987811
                36877714
                861a987c-a28a-4a48-b38e-e5788b272e09
                © 2023 Khor et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 7 September 2022
                : 20 February 2023
                Page count
                Figures: 0, Tables: 4, Pages: 14
                Product
                Funding
                The authors received no specific funding for this work.
                Categories
                Research Article
                Biology and Life Sciences
                Anatomy
                Body Fluids
                Mucus
                Sputum
                Medicine and Health Sciences
                Anatomy
                Body Fluids
                Mucus
                Sputum
                Biology and Life Sciences
                Physiology
                Body Fluids
                Mucus
                Sputum
                Medicine and Health Sciences
                Medical Conditions
                Infectious Diseases
                Bacterial Diseases
                Tuberculosis
                Medicine and Health Sciences
                Medical Conditions
                Tropical Diseases
                Tuberculosis
                Medicine and health sciences
                Diagnostic medicine
                HIV diagnosis and management
                Medicine and Health Sciences
                Diagnostic Medicine
                Tuberculosis Diagnosis and Management
                People and Places
                Geographical Locations
                Asia
                Malaysia
                Medicine and Health Sciences
                Endocrinology
                Endocrine Disorders
                Diabetes Mellitus
                Medicine and Health Sciences
                Medical Conditions
                Metabolic Disorders
                Diabetes Mellitus
                Medicine and Health Sciences
                Medical Conditions
                Infectious Diseases
                Bacterial Diseases
                Tuberculosis
                Extensively Drug-Resistant Tuberculosis
                Medicine and Health Sciences
                Medical Conditions
                Tropical Diseases
                Tuberculosis
                Extensively Drug-Resistant Tuberculosis
                Medicine and Health Sciences
                Medical Conditions
                Infectious Diseases
                Bacterial Diseases
                Tuberculosis
                Multi-Drug-Resistant Tuberculosis
                Medicine and Health Sciences
                Medical Conditions
                Tropical Diseases
                Tuberculosis
                Multi-Drug-Resistant Tuberculosis
                Custom metadata
                All relevant data are within the manuscript. Further data cannot be shared publicly because the data is owned by Ministry of Health Malaysia. Access to data can be requested from National Institutes of Health (NIH), Ministry of Health Malaysia (contact via email: jppnih@ 123456moh.gov.my ) and Medical Research and Ethics Committee (MREC) Malaysia (contact via email: mrecsec@ 123456moh.gov.my ) for researchers who meet the criteria for access to confidential data. The data underlying the results presented in the study are available from the Public Health Division, Sabah State Health deaprtment (contact via phone: +608-8512555). The authors did not have special access to the data and requested these data in the same manner after obtaining approval from NIH Malaysia and MREC Malaysia.

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