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      High TB burden and low notification rates in the Philippines: The 2016 national TB prevalence survey

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          Abstract

          Setting

          The 3 rd national tuberculosis (TB) survey in the Philippines in 2007 reported a significant decline in the prevalence of TB. Since then, more significant investments for TB control have been made, yet TB burden estimates from routine surveillance data remain relatively stable.

          Objective

          To estimate the prevalence of bacteriologically confirmed pulmonary TB in the Philippines amongst individuals aged ≥15 years in 2016.

          Design

          In March–December 2016, we conducted a population-based survey with stratified, multi-stage cluster sampling of residents in 106 clusters aged ≥15 years. Survey participants were screened for TB by symptom-based interview and digital chest X-ray. Those with cough ≥2 weeks and/or haemoptysis and/or chest X-ray suggestive of TB were requested to submit 2 sputum specimens for Xpert MTB/RIF, direct sputum smear microscopy using LED fluorescent microscopy, and mycobacterial solid culture (Ogawa method). Bacteriologically confirmed pulmonary TB was defined as MTB culture positive and/or Xpert positive.

          Results

          There were 46,689 individuals interviewed, and 41,444 (88.8%) consented to a chest X-ray. There were 18,597 (39.8%) eligible for sputum examination and 16,242 (87.3%) submitted at least one specimen. Out of 16,058 sputum-eligible participants, 183 (1.1%) were smear-positive. There were 466 bacteriologically confirmed TB cases: 238 (51.1%) Xpert positive, 69 (14.8%) culture positive, and 159 (34.1%) positive by both Xpert and culture. The estimated TB prevalence per 100,000 population aged ≥15 years was 434 (95% CI: 350−518) for smear-positive TB, and 1,159 (95% CI: 1,016−1,301) for bacteriologically confirmed TB.

          Conclusion

          This nationally representative survey found that the TB burden in the Philippines in 2016 was higher than estimated from routine TB surveillance data. There was no evidence of a decline in smear and culture positive TB from the 2007 survey despite significant investments in TB control. New strategies for case-finding and patient-centered care must be intensified and expanded.

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          Most cited references19

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          Xpert MTB/RIF Ultra for detection of Mycobacterium tuberculosis and rifampicin resistance: a prospective multicentre diagnostic accuracy study

          Summary Background The Xpert MTB/RIF assay is an automated molecular test that has improved the detection of tuberculosis and rifampicin resistance, but its sensitivity is inadequate in patients with paucibacillary disease or HIV. Xpert MTB/RIF Ultra (Xpert Ultra) was developed to overcome this limitation. We compared the diagnostic performance of Xpert Ultra with that of Xpert for detection of tuberculosis and rifampicin resistance. Methods In this prospective, multicentre, diagnostic accuracy study, we recruited adults with pulmonary tuberculosis symptoms presenting at primary health-care centres and hospitals in eight countries (South Africa, Uganda, Kenya, India, China, Georgia, Belarus, and Brazil). Participants were allocated to the case detection group if no drugs had been taken for tuberculosis in the past 6 months or to the multidrug-resistance risk group if drugs for tuberculosis had been taken in the past 6 months, but drug resistance was suspected. Demographic information, medical history, chest imaging results, and HIV test results were recorded at enrolment, and each participant gave at least three sputum specimen on 2 separate days. Xpert and Xpert Ultra diagnostic performance in the same sputum specimen was compared with culture tests and drug susceptibility testing as reference standards. The primary objectives were to estimate and compare the sensitivity of Xpert Ultra test with that of Xpert for detection of smear-negative tuberculosis and rifampicin resistance and to estimate and compare Xpert Ultra and Xpert specificities for detection of rifampicin resistance. Study participants in the case detection group were included in all analyses, whereas participants in the multidrug-resistance risk group were only included in analyses of rifampicin-resistance detection. Findings Between Feb 18, and Dec 24, 2016, we enrolled 2368 participants for sputum sampling. 248 participants were excluded from the analysis, and 1753 participants were distributed to the case detection group (n=1439) and the multidrug-resistance risk group (n=314). Sensitivities of Xpert Ultra and Xpert were 63% and 46%, respectively, for the 137 participants with smear-negative and culture-positive sputum (difference of 17%, 95% CI 10 to 24); 90% and 77%, respectively, for the 115 HIV-positive participants with culture-positive sputum (13%, 6·4 to 21); and 88% and 83%, respectively, across all 462 participants with culture-positive sputum (5·4%, 3·3 to 8·0). Specificities of Xpert Ultra and Xpert for case detection were 96% and 98% (−2·7%, −3·9 to −1·7) overall, and 93% and 98% for patients with a history of tuberculosis. Xpert Ultra and Xpert performed similarly in detecting rifampicin resistance. Interpretation For tuberculosis case detection, sensitivity of Xpert Ultra was superior to that of Xpert in patients with paucibacillary disease and in patients with HIV. However, this increase in sensitivity came at the expense of a decrease in specificity. Funding Government of Netherlands, Government of Australia, Bill & Melinda Gates Foundation, Government of the UK, and the National Institute of Allergy and Infectious Diseases.
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            The global burden of tuberculosis: results from the Global Burden of Disease Study 2015

            Summary Background An understanding of the trends in tuberculosis incidence, prevalence, and mortality is crucial to tracking of the success of tuberculosis control programmes and identification of remaining challenges. We assessed trends in the fatal and non-fatal burden of tuberculosis over the past 25 years for 195 countries and territories. Methods We analysed 10 691 site-years of vital registration data, 768 site-years of verbal autopsy data, and 361 site-years of mortality surveillance data using the Cause of Death Ensemble model to estimate tuberculosis mortality rates. We analysed all available age-specific and sex-specific data sources, including annual case notifications, prevalence surveys, and estimated cause-specific mortality, to generate internally consistent estimates of incidence, prevalence, and mortality using DisMod-MR 2.1, a Bayesian meta-regression tool. We assessed how observed tuberculosis incidence, prevalence, and mortality differed from expected trends as predicted by the Socio-demographic Index (SDI), a composite indicator based on income per capita, average years of schooling, and total fertility rate. We also estimated tuberculosis mortality and disability-adjusted life-years attributable to the independent effects of risk factors including smoking, alcohol use, and diabetes. Findings Globally, in 2015, the number of tuberculosis incident cases (including new and relapse cases) was 10·2 million (95% uncertainty interval 9·2 million to 11·5 million), the number of prevalent cases was 10·1 million (9·2 million to 11·1 million), and the number of deaths was 1·3 million (1·1 million to 1·6 million). Among individuals who were HIV negative, the number of incident cases was 8·8 million (8·0 million to 9·9 million), the number of prevalent cases was 8·9 million (8·1 million to 9·7 million), and the number of deaths was 1·1 million (0·9 million to 1·4 million). Annualised rates of change from 2005 to 2015 showed a faster decline in mortality (–4·1% [–5·0 to –3·4]) than in incidence (–1·6% [–1·9 to –1·2]) and prevalence (–0·7% [–1·0 to –0·5]) among HIV-negative individuals. The SDI was inversely associated with HIV-negative mortality rates but did not show a clear gradient for incidence and prevalence. Most of Asia, eastern Europe, and sub-Saharan Africa had higher rates of HIV-negative tuberculosis burden than expected given their SDI. Alcohol use accounted for 11·4% (9·3–13·0) of global tuberculosis deaths among HIV-negative individuals in 2015, diabetes accounted for 10·6% (6·8–14·8), and smoking accounted for 7·8% (3·8–12·0). Interpretation Despite a concerted global effort to reduce the burden of tuberculosis, it still causes a large disease burden globally. Strengthening of health systems for early detection of tuberculosis and improvement of the quality of tuberculosis care, including prompt and accurate diagnosis, early initiation of treatment, and regular follow-up, are priorities. Countries with higher than expected tuberculosis rates for their level of sociodemographic development should investigate the reasons for lagging behind and take remedial action. Efforts to prevent smoking, alcohol use, and diabetes could also substantially reduce the burden of tuberculosis. Funding Bill & Melinda Gates Foundation.
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              The social determinants of tuberculosis: from evidence to action.

              Growing consensus indicates that progress in tuberculosis control in the low- and middle-income world will require not only investment in strengthening tuberculosis control programs, diagnostics, and treatment but also action on the social determinants of tuberculosis. However, practical ideas for action are scarcer than is notional support for this idea. We developed a framework based on the recent World Health Organization Commission on Social Determinants of Health and on current understanding of the social determinants of tuberculosis. Interventions from outside the health sector-specifically, in social protection and urban planning-have the potential to strengthen tuberculosis control.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Formal analysisRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: Project administrationRole: ResourcesRole: SupervisionRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: Formal analysisRole: InvestigationRole: MethodologyRole: SupervisionRole: Writing – original draft
                Role: ConceptualizationRole: Formal analysisRole: MethodologyRole: ValidationRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: Formal analysisRole: InvestigationRole: MethodologyRole: SupervisionRole: Writing – review & editing
                Role: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: SoftwareRole: VisualizationRole: Writing – review & editing
                Role: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: SoftwareRole: VisualizationRole: Writing – review & editing
                Role: Formal analysisRole: InvestigationRole: VisualizationRole: Writing – review & editing
                Role: InvestigationRole: MethodologyRole: Writing – review & editing
                Role: Formal analysisRole: InvestigationRole: Writing – review & editing
                Role: Formal analysisRole: InvestigationRole: Writing – review & editing
                Role: Formal analysisRole: InvestigationRole: MethodologyRole: Writing – review & editing
                Role: Data curationRole: MethodologyRole: ValidationRole: Writing – review & editing
                Role: Formal analysisRole: Writing – review & editing
                Role: Formal analysisRole: InvestigationRole: MethodologyRole: Writing – review & editing
                Role: Funding acquisitionRole: Project administrationRole: ResourcesRole: Writing – review & editing
                Role: Formal analysisRole: InvestigationRole: MethodologyRole: Writing – review & editing
                Role: Formal analysisRole: InvestigationRole: SupervisionRole: Writing – review & editing
                Role: Funding acquisitionRole: Project administrationRole: ResourcesRole: Writing – review & editing
                Role: ValidationRole: Writing – review & editing
                Role: ConceptualizationRole: Funding acquisitionRole: MethodologyRole: ResourcesRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS One
                plos
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                4 June 2021
                2021
                : 16
                : 6
                : e0252240
                Affiliations
                [1 ] Department of Clinical Epidemiology, College of Medicine, University of the Philippines, Manila, Philippines
                [2 ] Division of Infectious Diseases, Department of Medicine, College of Medicine, University of the Philippines–Philippine General Hospital, Manila, Philippines
                [3 ] Global Tuberculosis Programme, World Health Organization, Geneva, Switzerland
                [4 ] Institute of Clinical Epidemiology, National Institutes of Health, University of the Philippines, Manila, Philippines
                [5 ] Foundation for the Advancement of Clinical Epidemiology, Manila, Philippines
                [6 ] Social Innovation in Health Initiative, University of the Philippines, Manila, Philippines
                [7 ] Foundation for the Control of Infectious Diseases, Taft Avenue, Manila, Philippines
                [8 ] Department of Radiology, University of the Philippines College of Medicine, University of the Philippines, Manila, Philippines
                [9 ] Philippine College of Radiology, Quezon City, Philippines
                [10 ] Department of Health, National TB Control Program, Manila, Philippines
                [11 ] Institute of Health Policy and Development Studies, University of the Philippines, Manila, Philippines
                [12 ] Infectious Diseases Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Policlinico di Sant’Orsola, Bologna, Italy
                [13 ] Department of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna, Bologna, Italy
                The University of Georgia, UNITED STATES
                Author notes

                Competing Interests: The authors have declared that no competing interests exist. The authors alone are responsible for the views expressed in this article and they do not necessarily represent the views, decisions or policies of the institutions with which they are affiliated.

                ¶ Membership of the Philippine NTPS 2016 Group is provided in the Acknowledgments.

                Author information
                https://orcid.org/0000-0002-6606-0466
                https://orcid.org/0000-0003-0521-7754
                https://orcid.org/0000-0003-1723-712X
                https://orcid.org/0000-0003-1802-1021
                https://orcid.org/0000-0001-5407-1478
                Article
                PONE-D-21-01317
                10.1371/journal.pone.0252240
                8177416
                34086746
                3c083776-2185-451b-9408-d3636cdecf6d
                © 2021 Lansang 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
                : 13 January 2021
                : 11 May 2021
                Page count
                Figures: 4, Tables: 3, Pages: 16
                Funding
                Funded by: Department of Health, Republic of the Philippines
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/501100011096, Philippine Council for Health Research and Development;
                Award Recipient :
                The 2016 NTPS was supported by the Philippines’ Department of Health ( https://doh.gov.ph/) through a research grant from the Department of Science and Technology – Philippine Council for Health Research and Development ( http://pchrd.dost.gov.ph/), as covered by a Memorandum of Understanding dated 11 December 2015. The Department of Health and the Philippine Council for Health Research and Development were involved in the overall design of the survey and the decision to publish the survey results. Anna Marie Celina Garfin, programme manager of the National TB Control Programme of the Department of Health, is a co-author of the paper.
                Categories
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