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Ssekamatte P, Sitenda D, Nabatanzi R, Nakibuule M, Kibirige D, Kyazze AP, Kateete DP, Bagaya BS, Sande OJ, van Crevel R, Cose S, Biraro IA. Isoniazid preventive therapy modulates Mycobacterium tuberculosis-specific T-cell responses in individuals with latent tuberculosis and type 2 diabetes. Sci Rep 2025; 15:10423. [PMID: 40140681 PMCID: PMC11947150 DOI: 10.1038/s41598-025-95386-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2024] [Accepted: 03/20/2025] [Indexed: 03/28/2025] Open
Abstract
Diabetes mellitus (DM) is a significant contributor to tuberculosis (TB) incidence and poor treatment outcomes. This study explored the impact of isoniazid preventive therapy (IPT) on Mycobacterium tuberculosis (Mtb)-specific T-cell memory phenotypes and function among participants with latent TB infection and DM (LTBI-DM) at baseline and after 6 months of IPT; and compared the responses to healthy controls (HC). Peripheral blood mononuclear cells were stimulated with ESAT-6 and CFP-10 peptide pools to analyse CD4+ and CD8+ T-cell responses using flow cytometry. In LTBI-DM participants, effector memory CD4+ and CD8+ T cells were decreased post-IPT, suggesting a shift towards a less-activated state or differentiation into other subsets. CXCR5 expression on both CD4+ and CD8+ T cells was upregulated, while PD-1 expression was downregulated post-IPT, indicating reduced T-cell exhaustion and improved homing capabilities. Lastly, IL-17 A and IL-13 production in CD4+ and CD8+ T cells was increased post-IPT, respectively, which play a role in enhanced Mtb infection control. The post-IPT T-cell alterations were similar to normal HC levels. These findings suggest that IPT modulates and normalises specific T-cell memory phenotypes and functional responses in LTBI-DM participants, potentially contributing to improved long-term immunity and protection against TB. This study highlights the importance of preventive therapy in high-risk populations, and larger studies with more extended follow-up are needed to assess long-lasting IPT effects.
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Affiliation(s)
- Phillip Ssekamatte
- Department of Immunology and Molecular Biology, School of Biomedical Sciences, College of Health Sciences, Makerere University, Kampala, Uganda.
- Medical Research Council/Uganda Virus Research Institute and London School of Hygiene & Tropical Medicine Uganda Research Unit, Entebbe, Uganda.
| | - Diana Sitenda
- Department of Immunology and Molecular Biology, School of Biomedical Sciences, College of Health Sciences, Makerere University, Kampala, Uganda
| | - Rose Nabatanzi
- Department of Immunology and Molecular Biology, School of Biomedical Sciences, College of Health Sciences, Makerere University, Kampala, Uganda
| | - Marjorie Nakibuule
- Medical Research Council/Uganda Virus Research Institute and London School of Hygiene & Tropical Medicine Uganda Research Unit, Entebbe, Uganda
| | - Davis Kibirige
- Department of Medicine, Uganda Martyrs Hospital Lubaga, Kampala, Uganda
| | - Andrew Peter Kyazze
- Department of Internal Medicine, School of Medicine, College of Health Sciences, Makerere University, Kampala, Uganda
| | - David Patrick Kateete
- Department of Immunology and Molecular Biology, School of Biomedical Sciences, College of Health Sciences, Makerere University, Kampala, Uganda
| | - Bernard Ssentalo Bagaya
- Department of Immunology and Molecular Biology, School of Biomedical Sciences, College of Health Sciences, Makerere University, Kampala, Uganda
| | - Obondo James Sande
- Department of Immunology and Molecular Biology, School of Biomedical Sciences, College of Health Sciences, Makerere University, Kampala, Uganda
| | - Reinout van Crevel
- Department of Internal Medicine and Radboud Centre for Infectious Diseases, Radboud University Medical Centre, Kampala, Uganda
| | - Stephen Cose
- Medical Research Council/Uganda Virus Research Institute and London School of Hygiene & Tropical Medicine Uganda Research Unit, Entebbe, Uganda
| | - Irene Andia Biraro
- Medical Research Council/Uganda Virus Research Institute and London School of Hygiene & Tropical Medicine Uganda Research Unit, Entebbe, Uganda
- Department of Internal Medicine, School of Medicine, College of Health Sciences, Makerere University, Kampala, Uganda
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Gonzalez-Muñiz OE, Rodriguez-Carlos A, Santos-Mena A, Jacobo-Delgado YM, Gonzalez-Curiel I, Rivas-Santiago C, Navarro-Tovar G, Rivas-Santiago B. Metformin modulates corticosteroids hormones in adrenals cells promoting Mycobacterium tuberculosis elimination in human macrophages. Tuberculosis (Edinb) 2024; 148:102548. [PMID: 39068772 DOI: 10.1016/j.tube.2024.102548] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2024] [Revised: 07/22/2024] [Accepted: 07/23/2024] [Indexed: 07/30/2024]
Abstract
Research suggests that both tuberculosis (TB) and type 2 diabetes mellitus (T2DM) have an immuno-endocrine imbalance characterized by dysregulated proinflammatory molecules and hormone levels (high cortisol/DHEA ratio), impeding an effective immune response against Mycobacterium tuberculosis (Mtb) driven by cytokines, antimicrobial peptides (AMPs), and androgens like DHEA. Insulin, sulfonylurea derivatives, and metformin are commonly used glucose-lowering drugs in patients suffering from TB and T2DM. For this comorbidity, metformin is an attractive target to restore the immunoendocrine mechanisms dysregulated against Mtb. This study aimed to assess whether metformin influences cortisol and DHEA synthesis in adrenal cells and if these hormones influence the expression of proinflammatory cytokines and AMPs in Mtb-infected macrophages. Our results suggest that metformin may enhance DHEA synthesis while maintaining cortisol homeostasis. In addition, supernatants from metformin-treated adrenal cells decreased mycobacterial loads in macrophages, which related to rising proinflammatory cytokines and AMP expression (HBD-2 and 3). Intriguingly, we find that HBD-3 and LL-37 can modulate steroid synthesis in adrenal cells with diminished levels of cortisol and DHEA, highlighting the importance of crosstalk communication between adrenal hormones and these effectors of innate immunity. We suggest that metformin's effects can promote innate immunity against Mtb straight or through modulation of corticosteroid hormones.
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Affiliation(s)
- Oscar E Gonzalez-Muñiz
- Biomedical Research Unit Zacatecas, Mexican Institute of Social Security-IMSS, Zacatecas, Mexico; Faculty of Chemical Sciences, Autonomous University of San Luis Potosí, S.L.P, Mexico
| | - Adrián Rodriguez-Carlos
- Biomedical Research Unit Zacatecas, Mexican Institute of Social Security-IMSS, Zacatecas, Mexico
| | - Alan Santos-Mena
- Biomedical Research Unit Zacatecas, Mexican Institute of Social Security-IMSS, Zacatecas, Mexico; Faculty of Chemical Sciences, Autonomous University of San Luis Potosí, S.L.P, Mexico
| | - Yolanda M Jacobo-Delgado
- Biomedical Research Unit Zacatecas, Mexican Institute of Social Security-IMSS, Zacatecas, Mexico
| | - Irma Gonzalez-Curiel
- Sciences and Chemical Technology, Chemistry Sciences School, Autonomous University of Zacatecas, Zacatecas, 98085, Mexico
| | - Cesar Rivas-Santiago
- CONAHCYT-Academic Unit of Chemical Sciences, Autonomous University of Zacatecas, Zacatecas, 98085, Mexico
| | | | - Bruno Rivas-Santiago
- Biomedical Research Unit Zacatecas, Mexican Institute of Social Security-IMSS, Zacatecas, Mexico.
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Song C, Zhao C, Nong Y, Lin Y, Huang A, Xi S, Wei X, Zeng C, Qin Y, Zhu Q. Exploring the accuracy of third-generation Nanopore Sequencing technology for detecting mycobacterium tuberculosis in patients with diabetes mellitus. Diagn Microbiol Infect Dis 2024; 110:116392. [PMID: 38875895 DOI: 10.1016/j.diagmicrobio.2024.116392] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2024] [Revised: 05/17/2024] [Accepted: 06/03/2024] [Indexed: 06/16/2024]
Abstract
OBJECTIVE To explore the diagnostic value of third-generation nanopore sequencing technology in patients with diabetes mellitus suspected of pulmonary tuberculosis. METHODS Samples, including sputum and bronchoalveolar lavage fluid(BALF), were collected from patients with diabetes mellitus suspected of pulmonary tuberculosis who were admitted from October 2021 to August 2023. Nanopore sequencing, acid-fast bacilli (AFB) smear, mycobacterial solid culture, Xpert MTB/RIF, and DNA detection were performed, and their diagnostic efficacy was compared. RESULTS Third-generation nanopore sequencing technology exhibited high accuracy in diagnosing pulmonary tuberculosis in patients with diabetes mellitus. Compared to traditional methods, nanopore sequencing showed significantly improved sensitivity (76.80 %), negative predictive value (30.40 %), coincidence (77.92 %), and diagnostic accuracy (AUC = 0.822). Combined detection with Xpert achieved the highest diagnostic performance, with increased sensitivity (81.20 %), positive predictive value (98.20 %), negative predictive value (35.00 %), coincidence (81.82 %), and AUC (0.843). Although acid-fast staining had limitations, its combination with nanopore sequencing improved screening effectiveness. CONCLUSION Compared to established diagnostic modalities such as acid-fast staining, mycobacterial solid culture, Xpert MTB/RIF, and DNA detection, third-generation nanopore sequencing technology demonstrates a significant improvement in sensitivity for detecting suspected pulmonary tuberculosis in diabetic patients. Notably, the combined application of nanopore sequencing with Xpert testing offers a further enhancement in diagnostic accuracy.
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Affiliation(s)
- Chang Song
- Department of Tuberculosis, The Fourth People's Hospital of Nanning, NO.1 Changgang-two-li Road, Nanning, Guangxi, China, 530023; Guangxi Medical University, Nanning, China
| | - Chunyan Zhao
- Department of Tuberculosis, The Fourth People's Hospital of Nanning, NO.1 Changgang-two-li Road, Nanning, Guangxi, China, 530023; Guangxi Medical University, Nanning, China
| | - Yingxing Nong
- Department of Medical, The Fourth People's Hospital of Nanning, NO.1 Changgang-two-li Road, Nanning, Guangxi, China, 530023
| | - Yanrong Lin
- Department of Tuberculosis, The Fourth People's Hospital of Nanning, NO.1 Changgang-two-li Road, Nanning, Guangxi, China, 530023
| | - Aichun Huang
- Department of Tuberculosis, The Fourth People's Hospital of Nanning, NO.1 Changgang-two-li Road, Nanning, Guangxi, China, 530023
| | - Shanyong Xi
- Department of Clinical Laboratory, The Fourth People's Hospital of Nanning, NO.1 Changgang-two-li Road, Nanning, Guangxi, China, 530023
| | - Xiaoying Wei
- Department of Tuberculosis, The Fourth People's Hospital of Nanning, NO.1 Changgang-two-li Road, Nanning, Guangxi, China, 530023
| | - Chunmei Zeng
- Department of Tuberculosis, The Fourth People's Hospital of Nanning, NO.1 Changgang-two-li Road, Nanning, Guangxi, China, 530023
| | - Yaqin Qin
- Administrative Office, The Fourth People's Hospital of Nanning, NO.1 Changgang-two-li Road, Nanning, Guangxi, China, 530023
| | - Qingdong Zhu
- Department of Tuberculosis, The Fourth People's Hospital of Nanning, NO.1 Changgang-two-li Road, Nanning, Guangxi, China, 530023.
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Kim KH, Kim HW, Kim YH, Park Y, Jung SS, Kim JW, Oh JY, Lee H, Kim SK, Kim SH, Lyu J, Ko Y, Kwon SJ, Jeong YJ, Kim DJ, Koo HK, Jegal Y, Kyung SY, Lee SS, Park JS, Kim JS, Min J. Effect of complicated, untreated and uncontrolled diabetes and pre-diabetes on treatment outcome among patients with pulmonary tuberculosis. Respirology 2024; 29:624-632. [PMID: 38539055 DOI: 10.1111/resp.14714] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2023] [Accepted: 03/14/2024] [Indexed: 06/20/2024]
Abstract
BACKGROUND AND OBJECTIVE Patients with tuberculosis and diabetes have a higher risk of unfavourable anti-tuberculosis treatment outcomes. In the present study, we aimed to evaluate the effects of various diabetes statuses on the outcomes of patients with pulmonary tuberculosis. METHODS Among the patients with pulmonary tuberculosis enrolled in the Korea Tuberculosis Cohort (KTBC) registry and the multicentre prospective cohort study of pulmonary tuberculosis (COSMOTB), those with diabetes and complicated diabetes were identified. The primary and secondary outcomes were unfavourable outcomes and mortality, respectively. The effect of diabetes and complicated diabetes on the outcomes was assessed using multivariable logistic regression analysis. Using COSMOTB, subgroup analyses were performed to assess the association between various diabetes statuses and outcomes. RESULTS In the KTBC, diabetes (adjusted odds ratio [aOR] = 1.93, 95% CI = 1.64-2.26) and complicated diabetes (aOR = 1.96, 95% CI = 1.67-2.30) were significantly associated with unfavourable outcomes, consistent with the COSMOTB data analysis. Based on subgroup analysis, untreated diabetes at baseline was an independent risk factor for unfavourable outcomes (aOR = 2.72, 95% CI = 1.26-5.61). Prediabetes and uncontrolled diabetes increased unfavourable outcomes and mortality without statistical significance. CONCLUSION Untreated and complicated diabetes at the time of tuberculosis diagnosis increases the risk of unfavourable outcomes and mortality.
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Affiliation(s)
- Kyung Hoon Kim
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Hyung Woo Kim
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Yong Hyun Kim
- Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Bucheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Yeonhee Park
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Daejeon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Sung Soo Jung
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Chungnam National University Hospital, Daejeon, Republic of Korea
| | - Jin Woo Kim
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Uijeongbu St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Jee Youn Oh
- Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Internal Medicine, Korea University Guro Hospital, Korea University College of Medicine, Seoul, Republic of Korea
| | - Heayon Lee
- Division of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, Eunpyeong St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Sung Kyoung Kim
- Division of Pulmonology, Department of Internal Medicine, St. Vincent's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Sun-Hyung Kim
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Chungbuk National University Hospital, Cheongju, Republic of Korea
| | - Jiwon Lyu
- Department of Pulmonary and Critical Care Medicine, Soonchunhyang University Cheonan Hospital, Soonchunhyang University College of Medicine, Cheonan, Republic of Korea
| | - Yousang Ko
- Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Kangdong Sacred Heart Hospital, Hallym University College of Medicine, Seoul, Republic of Korea
| | - Sun Jung Kwon
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Konyang University Hospital, Konyang University College of Medicine, Daejeon, Korea
| | - Yun-Jeong Jeong
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Dongguk University Ilsan Hospital, Goyang, Republic of Korea
| | - Do Jin Kim
- Division of Allergy and Respiratory Medicine, Soonchunhyang University Bucheon Hospital, Soonchunhyang University College of Medicine, Bucheon, Republic of Korea
| | - Hyeon-Kyoung Koo
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Ilsan Paik Hospital, Inje University College of Medicine, Goyang, Republic of Korea
| | - Yangjin Jegal
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Ulsan University Hospital, Ulsan University College of Medicine, Ulsan, Republic of Korea
| | - Sun Young Kyung
- Division of Pulmonology, Department of Internal Medicine, Gachon University Gil Hospital, Incheon, Republic of Korea
| | - Sung Soon Lee
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Ilsan Paik Hospital, Inje University College of Medicine, Goyang, Republic of Korea
| | - Jae Seuk Park
- Division of Pulmonology, Department of Internal Medicine, Dankook University College of Medicine, Cheonan, Republic of Korea
| | - Ju Sang Kim
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Jinsoo Min
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
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Al-Bari MAA, Peake N, Eid N. Tuberculosis-diabetes comorbidities: Mechanistic insights for clinical considerations and treatment challenges. World J Diabetes 2024; 15:853-866. [PMID: 38766427 PMCID: PMC11099355 DOI: 10.4239/wjd.v15.i5.853] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/09/2024] [Revised: 02/08/2024] [Accepted: 03/21/2024] [Indexed: 05/10/2024] Open
Abstract
Tuberculosis (TB) remains a leading cause of death among infectious diseases, particularly in poor countries. Viral infections, multidrug-resistant and ex-tensively drug-resistant TB strains, as well as the coexistence of chronic illnesses such as diabetes mellitus (DM) greatly aggravate TB morbidity and mortality. DM [particularly type 2 DM (T2DM)] and TB have converged making their control even more challenging. Two contemporary global epidemics, TB-DM behaves like a syndemic, a synergistic confluence of two highly prevalent diseases. T2DM is a risk factor for developing more severe forms of multi-drug resistant-TB and TB recurrence after preventive treatment. Since a bidirectional relationship exists between TB and DM, it is necessary to concurrently treat both, and promote recommendations for the joint management of both diseases. There are also some drug-drug interactions resulting in adverse treatment outcomes in TB-DM patients including treatment failure, and reinfection. In addition, autophagy may play a role in these comorbidities. Therefore, the TB-DM comorbidities present several health challenges, requiring a focus on multidisciplinary collaboration and integrated strategies, to effectively deal with this double burden. To effectively manage the comorbidity, further screening in affected countries, more suitable drugs, and better treatment strategies are required.
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Affiliation(s)
| | - Nicholas Peake
- Biosciences and Chemistry and Biomolecular Research Centre, Sheffield Hallam University, Sheffield S1 1WB, United Kingdom
| | - Nabil Eid
- Department of Anatomy, Division of Human Biology, School of Medicine, International Medical University, Kuala Lumpur 57000, Malaysia
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Yamanaka T, Castro MC, Ferrer JP, Solon JA, Cox SE, Laurence YV, Vassall A. Costs incurred by people with co-morbid tuberculosis and diabetes and their households in the Philippines. PLoS One 2024; 19:e0297342. [PMID: 38271328 PMCID: PMC10810501 DOI: 10.1371/journal.pone.0297342] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2023] [Accepted: 01/02/2024] [Indexed: 01/27/2024] Open
Abstract
OBJECTIVE Diabetes is a risk factor for TB mortality and relapse. The Philippines has a high TB incidence with co-morbid diabetes. This study assessed the pre- and post-TB diagnosis costs incurred by people with TB and diabetes (TB-DM) and their households in the Philippines. METHODS Longitudinal data was collected for costs, income, and coping mechanisms of TB-affected households in Negros Occidental and Cebu, the Philippines. Data collection was conducted four times during TB treatment. The data collection tools were developed by adapting WHO's cross-sectional questionnaire in the Tuberculosis Patient Cost Surveys: A Handbook into a longitudinal study design. Demographic and clinical characteristics, self-reported household income, number of facility visits, patient costs, the proportion of TB-affected households facing catastrophic costs due to TB (>20% of annual household income before TB), coping mechanisms, and social support received were compared by diabetes status at the time of TB diagnosis. RESULTS 530 people with TB were enrolled in this study, and 144 (27.2%) had TB-DM based on diabetes testing at the time of TB diagnosis. 75.4% of people with TB-DM were more than 45 years old compared to 50.3% of people with TB-only (p<0.001). People with TB-DM had more frequent visits for TB treatment (120 vs 87 visits, p = 0.054) as well as for total visits for TB-DM treatment (129 vs 88 visits, p = 0.010) compared to those with TB-only. There was no significant difference in the proportion of TB-affected households facing catastrophic costs between those with TB-DM (76.3%) and those with TB-only (68.7%, p = 0.691). CONCLUSION People with TB-DM in the Philippines face extensive health service use. However, this does not translate into substantial differences in the incidence of catastrophic cost. Further study is required to understand the incidence of catastrophic costs due to diabetes-only in the Philippines.
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Affiliation(s)
- Takuya Yamanaka
- Department of Global Health and Development, London School of Hygiene and Tropical Medicine, London, United Kingdom
- School of Tropical Medicine and Global Health, Nagasaki University, Nagasaki, Japan
| | | | | | | | - Sharon E. Cox
- School of Tropical Medicine and Global Health, Nagasaki University, Nagasaki, Japan
- Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, United Kingdom
- Institute of Tropical Medicine, Nagasaki University (NEKKEN), Nagasaki, Japan
- UK Health Security Agency, London, United Kingdom
| | - Yoko V. Laurence
- Department of Global Health and Development, London School of Hygiene and Tropical Medicine, London, United Kingdom
- Health Economics for Life Sciences and Medicine, Department of Population Health Sciences, King’s College London, London, United Kingdom
| | - Anna Vassall
- Department of Global Health and Development, London School of Hygiene and Tropical Medicine, London, United Kingdom
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Oliveira Hashiguchi L, Cox SE, Edwards T, Castro MC, Khan M, Liverani M. How can tuberculosis services better support patients with a diabetes co-morbidity? A mixed methods study in the Philippines. BMC Health Serv Res 2023; 23:1027. [PMID: 37749519 PMCID: PMC10519082 DOI: 10.1186/s12913-023-10015-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2023] [Accepted: 09/08/2023] [Indexed: 09/27/2023] Open
Abstract
BACKGROUND People with diabetes mellitus (DM) have an estimated two- to three-times greater risk of adverse tuberculosis (TB) treatment outcomes compared to those without DM. Blood glucose control is a primary aim of managing DM during TB treatment, yet TB programmes are not generally adapted to provide DM services. The purpose of this study was to understand perceptions and the lived experiences of diabetic patients in TB treatment in the Philippines, with a view to informing the development of disease co-management strategies. METHODS This mixed methods study was conducted within a prospective cohort of adults newly-starting treatment for drug-sensitive and drug-resistant TB at 13 public TB clinics in three regions of the Philippines. Within the subset of 189 diabetic persons who self-reported a prior DM diagnosis, or were diagnosed by screenings conducted through the TB clinic, longitudinal blood glucose data were used to ascertain individuals' glycaemic control (controlled or uncontrolled). Univariable logistic regression analyses exploring associations between uncontrolled glycaemia and demographic and clinical factors informed purposive sampling of 31 people to participate in semi-structured interviews. All audio-recorded data were transcribed and thematic analysis performed. RESULTS Participants - both with controlled and uncontrolled blood glucose - were knowledgeable about diabetes and its management. However, a minority of participants were aware of the impact of DM on TB treatment and outcomes. Many participants newly-diagnosed with DM at enrolment in TB treatment had not perceived any diabetic symptoms prior and would have likely not sought clinical consult otherwise. Access to free glucose-lowering medications through TB clinics was a key enabling resource. However, participants expressed fear of side effects and interrupted access to glucose-lowering medications, and a preference for phytotherapy. Many participants felt that physical and financial impacts of TB and its treatment were challenges to DM management. CONCLUSIONS AND RECOMMENDATIONS Results of this study indicate that public TB clinics can provide diabetic patients with additional health care resources and education to address co-morbidity. TB programmes might consider identifying patients with complicated DM, and offering diabetic monitoring and management, as DM and diabetic complications may compound the burden of TB and its treatment.
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Affiliation(s)
- Lauren Oliveira Hashiguchi
- National Institute of Nursing Research, National Institutes of Health, 31 Center Drive, Bethesda, MD, 20892-2178, USA.
- Faculty of Public Health and Policy, London School of Hygiene & Tropical Medicine, Keppel St, London, WC1E 7HT, UK.
- School of Tropical Medicine & Global Health, Nagasaki University, 1 Chome-12-4 Sakamoto, Nagasaki, 852-8523, Japan.
| | - Sharon E Cox
- School of Tropical Medicine & Global Health, Nagasaki University, 1 Chome-12-4 Sakamoto, Nagasaki, 852-8523, Japan
- Faculty of Epidemiology & Population Health, London School of Hygiene & Tropical Medicine, Keppel St, London, WC1E 7HT, UK
- United Kingdom Health Security Agency, 61 Colindale Avenue London NW9 5EQ, Collindale, UK
| | - Tansy Edwards
- School of Tropical Medicine & Global Health, Nagasaki University, 1 Chome-12-4 Sakamoto, Nagasaki, 852-8523, Japan
- MRC International Statistics and Epidemiology Group, London School of Hygiene & Tropical Medicine, Keppel St, London, WC1E 7HT, UK
| | - Mary C Castro
- Nutrition Center Philippines, Muntinlupa City, Manila, Philippines
| | - Mishal Khan
- Faculty of Public Health and Policy, London School of Hygiene & Tropical Medicine, Keppel St, London, WC1E 7HT, UK
- Aga Khan University, National Stadium Road, Karachi, 74800, Pakistan
| | - Marco Liverani
- Faculty of Public Health and Policy, London School of Hygiene & Tropical Medicine, Keppel St, London, WC1E 7HT, UK
- School of Tropical Medicine & Global Health, Nagasaki University, 1 Chome-12-4 Sakamoto, Nagasaki, 852-8523, Japan
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Alffenaar JWC, Stocker SL, Forsman LD, Garcia-Prats A, Heysell SK, Aarnoutse RE, Akkerman OW, Aleksa A, van Altena R, de Oñata WA, Bhavani PK, Van't Boveneind-Vrubleuskaya N, Carvalho ACC, Centis R, Chakaya JM, Cirillo DM, Cho JG, D Ambrosio L, Dalcolmo MP, Denti P, Dheda K, Fox GJ, Hesseling AC, Kim HY, Köser CU, Marais BJ, Margineanu I, Märtson AG, Torrico MM, Nataprawira HM, Ong CWM, Otto-Knapp R, Peloquin CA, Silva DR, Ruslami R, Santoso P, Savic RM, Singla R, Svensson EM, Skrahina A, van Soolingen D, Srivastava S, Tadolini M, Tiberi S, Thomas TA, Udwadia ZF, Vu DH, Zhang W, Mpagama SG, Schön T, Migliori GB. Clinical standards for the dosing and management of TB drugs. Int J Tuberc Lung Dis 2022; 26:483-499. [PMID: 35650702 PMCID: PMC9165737 DOI: 10.5588/ijtld.22.0188] [Citation(s) in RCA: 43] [Impact Index Per Article: 14.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2022] [Accepted: 04/04/2022] [Indexed: 12/16/2022] Open
Abstract
BACKGROUND: Optimal drug dosing is important to ensure adequate response to treatment, prevent development of drug resistance and reduce drug toxicity. The aim of these clinical standards is to provide guidance on 'best practice´ for dosing and management of TB drugs.METHODS: A panel of 57 global experts in the fields of microbiology, pharmacology and TB care were identified; 51 participated in a Delphi process. A 5-point Likert scale was used to score draft standards. The final document represents the broad consensus and was approved by all participants.RESULTS: Six clinical standards were defined: Standard 1, defining the most appropriate initial dose for TB treatment; Standard 2, identifying patients who may be at risk of sub-optimal drug exposure; Standard 3, identifying patients at risk of developing drug-related toxicity and how best to manage this risk; Standard 4, identifying patients who can benefit from therapeutic drug monitoring (TDM); Standard 5, highlighting education and counselling that should be provided to people initiating TB treatment; and Standard 6, providing essential education for healthcare professionals. In addition, consensus research priorities were identified.CONCLUSION: This is the first consensus-based Clinical Standards for the dosing and management of TB drugs to guide clinicians and programme managers in planning and implementation of locally appropriate measures for optimal person-centred treatment to improve patient care.
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Affiliation(s)
- J W C Alffenaar
- Sydney Institute for Infectious Diseases, The University of Sydney, Sydney, NSW, Australia, School of Pharmacy, The University of Sydney Faculty of Medicine and Health, Sydney, NSW, Australia, Westmead Hospital, Sydney, NSW, Australia
| | - S L Stocker
- School of Pharmacy, The University of Sydney Faculty of Medicine and Health, Sydney, NSW, Australia, Department of Clinical Pharmacology and Toxicology, St Vincent´s Hospital, Sydney, NSW, Australia, St Vincent´s Clinical Campus, University of NSW, Kensington, NSW, Australia
| | - L Davies Forsman
- Division of Infectious Diseases, Department of Medicine, Karolinska Institutet, Solna, Sweden, Department of Infectious Diseases Karolinska University Hospital, Solna, Sweden
| | - A Garcia-Prats
- Desmond Tutu TB Centre, Department of Paediatrics and Child Health, Stellenbosch University, Tygerberg, South Africa, Department of Pediatrics, University of Wisconsin, Madison, WI
| | - S K Heysell
- Division of Infectious Diseases and International Health, University of Virginia, Charlottesville, VA, USA
| | - R E Aarnoutse
- Department of Pharmacy, Radboud Institute for Health Sciences & Radboudumc Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, The Netherlands
| | - O W Akkerman
- University of Groningen, University Medical Center Groningen, Department of Pulmonary Diseases and Tuberculosis, Groningen, The Netherlands, University of Groningen, University Medical Center Groningen, Tuberculosis Center Beatrixoord, Haren, The Netherlands
| | - A Aleksa
- Educational Institution "Grodno State Medical University", Grodno, Belarus
| | - R van Altena
- Asian Harm Reduction Network (AHRN) and Medical Action Myanmar (MAM) in Yangon, Myanmar
| | - W Arrazola de Oñata
- Belgian Scientific Institute for Public Health (Belgian Lung and Tuberculosis Association), Brussels, Belgium
| | - P K Bhavani
- Indian Council of Medical Research-National Institute for Research in Tuberculosis-International Center for Excellence in Research, Chennai, India
| | - N Van't Boveneind-Vrubleuskaya
- Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands, Department of Public Health TB Control, Metropolitan Public Health Services, The Hague, The Netherlands
| | - A C C Carvalho
- Laboratório de Inovações em Terapias, Ensino e Bioprodutos (LITEB), Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, RJ, Brazil
| | - R Centis
- Servizio di Epidemiologia Clinica delle Malattie Respiratorie, Istituti Clinici Scientifici Maugeri Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Tradate, Italy
| | - J M Chakaya
- Department of Medicine, Therapeutics and Dermatology, Kenyatta University, Nairobi, Kenya, Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, UK
| | - D M Cirillo
- Emerging Bacterial Pathogens Unit, Division of Immunology, Transplantation and Infectious Diseases, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - J G Cho
- Sydney Institute for Infectious Diseases, The University of Sydney, Sydney, NSW, Australia, Westmead Hospital, Sydney, NSW, Australia, Parramatta Chest Clinic, Parramatta, NSW, Australia
| | - L D Ambrosio
- Public Health Consulting Group, Lugano, Switzerland
| | - M P Dalcolmo
- Reference Center Hélio Fraga, Fundação Oswaldo Cruz (Fiocruz), Rio de Janeiro, RJ, Brazil
| | - P Denti
- Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa
| | - K Dheda
- Centre for Lung Infection and Immunity, Department of Medicine, Division of Pulmonology and UCT Lung Institute, University of Cape Town, Cape Town, South Africa, University of Cape Town Lung Institute & South African MRC Centre for the Study of Antimicrobial Resistance, Cape Town, South Africa, Faculty of Infectious and Tropical Diseases, Department of Immunology and Infection, London School of Hygiene & Tropical Medicine, London, UK
| | - G J Fox
- Faculty of Medicine and Health, Sydney Medical School, The University of Sydney, Sydney, NSW, Australia, Woolcock Institute of Medical Research, Glebe, NSW, Australia
| | - A C Hesseling
- Desmond Tutu TB Centre, Department of Paediatrics and Child Health, Stellenbosch University, Tygerberg, South Africa
| | - H Y Kim
- Sydney Institute for Infectious Diseases, The University of Sydney, Sydney, NSW, Australia, School of Pharmacy, The University of Sydney Faculty of Medicine and Health, Sydney, NSW, Australia, Westmead Hospital, Sydney, NSW, Australia
| | - C U Köser
- Department of Genetics, University of Cambridge, Cambridge, UK
| | - B J Marais
- Sydney Institute for Infectious Diseases, The University of Sydney, Sydney, NSW, Australia, Department of Infectious Diseases and Microbiology, The Children´s Hospital at Westmead, Westmead, NSW, Australia
| | - I Margineanu
- Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| | - A G Märtson
- Antimicrobial Pharmacodynamics and Therapeutics, Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool, UK
| | - M Munoz Torrico
- Clínica de Tuberculosis, Instituto Nacional de Enfermedades Respiratorias, Ciudad de México, Mexico
| | - H M Nataprawira
- Division of Paediatric Respirology, Department of Child Health, Faculty of Medicine, Universitas Padjadjaran, Hasan Sadikin Hospital, Bandung, Indonesia
| | - C W M Ong
- Infectious Disease Translational Research Programme, Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Institute for Health Innovation & Technology (iHealthtech), National University of Singapore, Singapore, Division of Infectious Diseases, Department of Medicine, National University Hospital, Singapore
| | - R Otto-Knapp
- German Central Committee against Tuberculosis (DZK), Berlin, Germany
| | - C A Peloquin
- Infectious Disease Pharmacokinetics Laboratory, Pharmacotherapy and Translational Research, University of Florida College of Pharmacy, Gainesville, FL, USA
| | - D R Silva
- Faculdade de Medicina, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil
| | - R Ruslami
- TB/HIV Research Centre, Faculty of Medicine, Universitas Padjadjaran, Bandung, Indonesia, Department of Biomedical Sciences, Division of Pharmacology and Therapy, Faculty of Medicine, Universitas Padjadjaran, Bandung, Indonesia
| | - P Santoso
- Division of Respirology and Critical Care, Department of Internal Medicine, Faculty of Medicine, Universitas Padjadjaran/Hasan Sadikin General Hospital, Bandung, Indonesia
| | - R M Savic
- Department of Bioengineering and Therapeutic Sciences, Division of Pulmonary and Critical Care Medicine, Schools of Pharmacy and Medicine, University of California San Francisco, San Francisco, CA, USA
| | - R Singla
- Department of TB & Respiratory Diseases, National Institute of TB & Respiratory Diseases, New Delhi, India
| | - E M Svensson
- Department of Pharmacy, Radboud Institute for Health Sciences & Radboudumc Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, The Netherlands, Department of Pharmacy, Uppsala University, Uppsala, Sweden
| | - A Skrahina
- The Republican Research and Practical Centre for Pulmonology and TB, Minsk, Belarus
| | - D van Soolingen
- National Institute for Public Health and the Environment, TB Reference Laboratory (RIVM), Bilthoven, The Netherlands
| | - S Srivastava
- Department of Pulmonary Immunology, University of Texas Health Science Center at Tyler, Tyler, TX, USA
| | - M Tadolini
- Infectious Diseases Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy, Department of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna, Bologna, Italy
| | - S Tiberi
- Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK
| | - T A Thomas
- Division of Infectious Diseases and International Health, University of Virginia, Charlottesville, VA, USA
| | - Z F Udwadia
- P. D. Hinduja National Hospital and Medical Research Centre, Mumbai, India
| | - D H Vu
- National Drug Information and Adverse Drug Reaction Monitoring Centre, Hanoi University of Pharmacy, Hanoi, Vietnam
| | - W Zhang
- Department of Infectious Diseases, National Medical Center for Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, People´s Republic of China
| | - S G Mpagama
- Kilimanjaro Christian Medical University College, Moshi, United Republic of Tanzania, Kibong´oto Infectious Diseases Hospital, Sanya Juu, Siha, Kilimanjaro, United Republic of Tanzania
| | - T Schön
- Department of Infectious Diseases, Linköping University Hospital, Linköping, Sweden, Institute of Biomedical and Clinical Sciences, Division of Infection and Inflammation, Linköping University, Linköping, Sweden, Department of Infectious Diseases, Kalmar County Hospital, Kalmar, Linköping University, Linköping, Sweden
| | - G B Migliori
- Servizio di Epidemiologia Clinica delle Malattie Respiratorie, Istituti Clinici Scientifici Maugeri Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Tradate, Italy
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Impact of diabetes mellitus on rifampicin's plasma concentration and bioavailability in patients with tuberculosis: A systematic review and meta-analysis study. Therapie 2022; 78:313-324. [DOI: 10.1016/j.therap.2022.05.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2022] [Revised: 02/27/2022] [Accepted: 05/16/2022] [Indexed: 11/19/2022]
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10
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Metwally AS, El-Sheikh SMA, Galal AAA. The impact of diabetes mellitus on the pharmacokinetics of rifampicin among tuberculosis patients: A systematic review and meta-analysis study. Diabetes Metab Syndr 2022; 16:102410. [PMID: 35144181 DOI: 10.1016/j.dsx.2022.102410] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/25/2021] [Revised: 01/15/2022] [Accepted: 01/18/2022] [Indexed: 11/26/2022]
Abstract
BACKGROUND AND AIMS Diabetes mellitus has a negative impact on the treatment outcome of tuberculosis, increasing the incidence of treatment failure and relapse. There is a scarcity of knowledge concerning the impact of diabetes mellitus on the pharmacokinetics of rifampicin. This study was conducted to evaluate the impact of diabetes mellitus on the pharmacokinetics of rifampicin among patients with tuberculosis. METHODS We explored the Web of Science, Cochrane Library, PubMed, and Scopus databases for articles that reported the pharmacokinetic parameters of rifampicin in diabetic and nondiabetic patients with tuberculosis published until September 2020. Based on the presence or absence of heterogeneity, pooled estimates were calculated using a random or fixed effect model. RESULTS Seven studies were relevant and included in this study. The Tmax of rifampicin increased in diabetic patients with tuberculosis compared with nondiabetic patients with tuberculosis (MD 0.84, 95% CI (0.32, 1.35), p = 0.002). No significant differences were detected in rifampicin Cmax (MD 0.18, 95% CI (-0.52, 0.88), p = 0.61), AUC0-24 (SMD -0.02, 95% CI (-0.34, 0.30), p = 0.90), Vd (MD -3.89, 95% CI (-11.17, 3.38), p = 0.29), CL (MD -0.13, 95%CI (-0.88, 0.61), p = 0.72), and MRT (MD 1.89, 95% CI (-0.03, 3.81), p = 0.05) between diabetic and nondiabetic patients with tuberculosis. CONCLUSION Diabetes mellitus increased the Tmax of rifampicin without further impact on other rifampicin pharmacokinetic parameters such as Cmax, AUC0-24, Vd, CL and MRT. Early therapeutic drug monitoring of rifampicin is necessary for diabetic tuberculosis patients.
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Affiliation(s)
- Amera Sh Metwally
- Zagazig University Hospitals, Zagazig University, 44519, Zagazig, Egypt.
| | - Sawsan M A El-Sheikh
- Professor of Pharmacology, Department of Pharmacology, Faculty of Veterinary Medicine, Zagazig University, 44519, Zagazig, Egypt
| | - Azza A A Galal
- Professor of Pharmacology, Department of Pharmacology, Faculty of Veterinary Medicine, Zagazig University, 44519, Zagazig, Egypt
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11
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Wu Q, Wang M, Zhang Y, Wang W, Ye TF, Liu K, Chen SH. Epidemiological Characteristics and Their Influencing Factors Among Pulmonary Tuberculosis Patients With and Without Diabetes Mellitus: A Survey Study From Drug Resistance Surveillance in East China. Front Public Health 2022; 9:777000. [PMID: 35141185 PMCID: PMC8818727 DOI: 10.3389/fpubh.2021.777000] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2021] [Accepted: 12/14/2021] [Indexed: 11/23/2022] Open
Abstract
Background The burden of pulmonary tuberculosis (TB) and diabetes mellitus (DM) have become serious global concerns, while the comprehensive evaluations of DM status and drug resistance in TB patients are still lacking. Methods All details of TB cases were collected from drug resistance monitoring sentinels in Zhejiang province. Fisher's exact test or Pearson chi-square test (χ2) was used to compare the baseline characteristics among TB with different DM statuses. The logistic regression model was used to estimate the relationship between DM and different drug resistance spectra. Univariate analysis and multivariate logistic model were used to explore the possible risk factors of drug resistance in TB patients with DM and no DM. Results 936 TB cases with smear-positive in Zhejiang province were collected, in which 76 patients (8.12%) owned the co-morbidity of DM. TB-DM prevalence was higher in older, Han nationality, employed, accompanied by no health insurance and hepatitis B status. Among 860 cases of TB-no DM and 76 cases of TB-DM, drug resistance-TB accounted for 31.51% and 23.68% (P > 0.05), MR-TB accounted for 15.93% and 14.47% (P > 0.05), respectively. MDR-TB was 4.88% and 6.58% (P > 0.05). The incidence of poly-drug resistant tuberculosis (PDR-TB) in TB-no DM patients (10.70 vs. 2.63%, OR: 4.43; 95% CI, 1.07–18.36) was higher than that in the TB-DM group (P < 0.05). In univariate and multivariate analysis, none of the basic factors were statistically significant with drug resistance among TB-DM cases (all P > 0.05). Retreatment was the risk factor of drug resistance among TB-no DM cases. Conclusions Our results showed that the drug resistance rate of the TB-DM group was not higher than that of the TB-no DM group. Patients with TB-no DM were at a higher risk for PDR-TB, but not for MDR-TB, MR-TB, and drug resistance-TB. Special attention should be paid to TB-no DM patients who have been previously treated. In the future, large-scale and well-designed prospective studies are needed to clarify the impact of DM on the drug-resistance among TB.
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Affiliation(s)
- Qian Wu
- Department of Tuberculosis Control and Prevention, Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou, China
| | - Min Wang
- Quzhou City Center Blood Station, Quzhou, China
| | - Yu Zhang
- Department of Tuberculosis Control and Prevention, Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou, China
| | - Wei Wang
- Department of Tuberculosis Control and Prevention, Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou, China
| | - Teng-Fei Ye
- Anhui No.2 Provincial People's Hospital, Hefei, China
| | - Kui Liu
- Department of Tuberculosis Control and Prevention, Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou, China
- *Correspondence: Kui Liu
| | - Song-Hua Chen
- Department of Tuberculosis Control and Prevention, Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou, China
- Song-Hua Chen
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12
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Hong L, Lin L, Chen J, Wu B. CT Image Features of the FBP Reconstruction Algorithm in the Evaluation of Fasting Blood Sugar Level of Diabetic Pulmonary Tuberculosis Patients and Early Diet Nursing. COMPUTATIONAL AND MATHEMATICAL METHODS IN MEDICINE 2021; 2021:1101930. [PMID: 34840593 PMCID: PMC8616654 DOI: 10.1155/2021/1101930] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/18/2021] [Revised: 10/22/2021] [Accepted: 11/02/2021] [Indexed: 11/18/2022]
Abstract
The study was aimed at exploring the application value of the CT image based on a filtered back projection (FBP) algorithm in the diagnosis of patients with diabetes complicated with tuberculosis and at analyzing the influence of dietary nursing on patients with diabetes complicated with tuberculosis. In this study, the FBP algorithm was used to optimize CT images to effectively obtain reconstructed ROI images. Then, the deviation from measurement values of reconstructed images at different pixel levels was analyzed. 138 patients with diabetes complicated with tuberculosis were selected as research subjects to compare the number of lung segments involved and the CT imaging manifestations at different fasting glucose levels. All patients were divided into the control group (routine drug treatment) and observation group (diet intervention on the basis of drug treatment) by random number table method, and the effect of different nursing methods on the improvement of patients' clinical symptoms was discussed. The results showed that the distance measurement value decreased with the increase in pixel level, there was no significant difference in the number of lung segments involved in patients with different fasting glucose levels (P > 0.05), and there were statistically significant differences in the incidence of segmental lobar shadow, bronchial air sign, wall-less cavity, thick-walled cavity, pulmonary multiple cavity, and bronchial tuberculosis in patients with different fasting glucose levels (P < 0.05). Compared with the control group, 2 h postprandial blood glucose level in the observation group was significantly improved (P < 0.05), there was a statistical significance in the number with reduced pleural effusion and the number with reduced tuberculosis foci in the two groups (P < 0.05), and the level of hemoglobin in the observation group was 7.1 ± 1.26, significantly lower than that in the control group (8.91 ± 2.03, P < 0.05). It suggested that the changes of CT images based on the FBP reconstruction algorithm were correlated with fasting blood glucose level. Personalized diet nursing intervention can improve the clinical symptoms of patients, which provides a reference for the clinical diagnosis and treatment of patients with diabetes complicated with tuberculosis.
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Affiliation(s)
- Lili Hong
- Pulmonary and Critical Care Medicine (PCCM), Quanzhou First Hospital, Quanzhou, 362000 Fujian, China
| | - Liling Lin
- Hospital Infection-Control Office, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, 362000 Fujian, China
| | - Jingping Chen
- Pulmonary and Critical Care Medicine (PCCM), Quanzhou First Hospital, Quanzhou, 362000 Fujian, China
| | - Biyu Wu
- Department of Nursing, Quanzhou First Hospital, Quanzhou, 362000 Fujian, China
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13
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Antonio-Arques V, Franch-Nadal J, Caylà JA. Diabetes and tuberculosis: A syndemic complicated by COVID-19. ACTA ACUST UNITED AC 2021; 157:288-293. [PMID: 34541325 PMCID: PMC8433042 DOI: 10.1016/j.medcle.2021.04.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2021] [Accepted: 04/13/2021] [Indexed: 11/25/2022]
Abstract
Tuberculosis (TB) is the leading cause of infectious mortality in the world, affecting mainly developing countries (DC), while diabetes (DM) is one of the most prevalent chronic diseases. This review analyzes the fact that diabetes is currently an important risk factor for developing TB, also presenting more complicated TB, more relapses and higher mortality. The DCs and the fourth world of the large cities are those with the highest incidence of TB and an increase in DM, which will make it difficult to control tuberculosis disease. At the same time, the COVID-19 pandemic is complicating the management of both diseases due to the difficulty of access to control and treatment and the worsening of socioeconomic inequalities. It is necessary to establish a bidirectional screening for TB and DM and promote recommendations for the joint management of both diseases.
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Affiliation(s)
- Violeta Antonio-Arques
- Institut Universitari per a la Recerca en Atenció Primària (IDIAP) Jordi Gol, Barcelona, Spain.,Equip d'Atenció Primària (EAP) Bordeta Magòria, Institut Català de la Salut, Barcelona, Spain
| | - Josep Franch-Nadal
- Institut Universitari per a la Recerca en Atenció Primària (IDIAP) Jordi Gol, Barcelona, Spain.,Equip d'Atenció Primària (EAP) Raval Sud - Drassanes, Institut Català de la Salut, Barcelona, Spain
| | - Joan A Caylà
- Fundación de la Unidad de Investigación en Tuberculosis de Barcelona, Barcelona, Spain
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Antonio-Arques V, Franch-Nadal J, Caylà JA. Diabetes and tuberculosis: a syndemic complicated by COVID-19. Med Clin (Barc) 2021; 157:288-293. [PMID: 34049681 PMCID: PMC8101986 DOI: 10.1016/j.medcli.2021.04.004] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2021] [Revised: 04/12/2021] [Accepted: 04/13/2021] [Indexed: 01/16/2023]
Abstract
Tuberculosis (TB) is the leading cause of infectious mortality in the world, affecting mainly developing countries (DC), while diabetes (DM) is one of the most prevalent chronic diseases. This review analyzes the fact that diabetes is currently an important risk factor for developing TB, also presenting more complicated TB, more relapses and higher mortality. The DCs and the fourth world of the large cities are those with the highest incidence of TB and an increase in DM, which will make it difficult to control tuberculosis disease. At the same time, the COVID-19 pandemic is complicating the management of both diseases due to the difficulty of access to control and treatment and the worsening of socioeconomic inequalities. It is necessary to establish a bidirectional screening for TB and DM and promote recommendations for the joint management of both diseases.
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Affiliation(s)
- Violeta Antonio-Arques
- Institut Universitari per a la Recerca en Atenció Primària (IDIAP) Jordi Gol, Barcelona, España; Equip d'Atenció Primària (EAP) Bordeta Magòria, Institut Català de la Salut, Barcelona, España
| | - Josep Franch-Nadal
- Institut Universitari per a la Recerca en Atenció Primària (IDIAP) Jordi Gol, Barcelona, España; Equip d'Atenció Primària (EAP) Raval Sud - Drassanes, Institut Català de la Salut, Barcelona, España.
| | - Joan A Caylà
- Fundación de la Unidad de Investigación en Tuberculosis de Barcelona, Barcelona, España
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15
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Mpagama SG, Ramaiya K, Lillebæk T, Mmbaga BT, Sumari-de Boer M, Ntinginya NE, Alffenaar JW, Heysell SK, Bygbjerg IC, Christensen DL. Protocol for establishing an Adaptive Diseases control Expert Programme in Tanzania (ADEPT) for integrating care of communicable and non-communicable diseases using tuberculosis and diabetes as a case study. BMJ Open 2021; 11:e041521. [PMID: 33910944 PMCID: PMC8094344 DOI: 10.1136/bmjopen-2020-041521] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/12/2020] [Revised: 02/04/2021] [Accepted: 04/12/2021] [Indexed: 12/12/2022] Open
Abstract
INTRODUCTION Most sub-Saharan African countries endure a high burden of communicable infections but also face a rise of non-communicable diseases (NCDs). Interventions targeting particular epidemics are often executed within vertical programmes. We establish an Adaptive Diseases control Expert Programme in Tanzania (ADEPT) model with three domains; stepwise training approach, integration of communicable and NCDs and a learning system. The model aims to shift traditional vertical programmes to an adaptive diseases management approach through integrating communicable and NCDs using the tuberculosis (TB) and diabetes mellitus (DM) dual epidemic as a case study. We aim to describe the ADEPT protocol with underpinned implementation and operational research on TB/DM. METHODS AND ANALYSIS The model implement a collaborative TB and DM services protocol as endorsed by WHO in Tanzania. Evaluation of the process and outcomes will follow the logic framework. A mixed research design with both qualitative and quantitative approaches will be used in applied research action. Anticipated implementation research outcomes include at the health facilities level for organising TB/DM services, pathways of patients with TB/DM seeking care in different health facilities, factors in service delivery that need deimplementation and the ADEPT model implementation feasibility, acceptability and fidelity. Expected operational research outcomes include additional identified patients with dual TB/DM, the prevalence of comorbidities like hypertension in patients with TB/DM and final treatment outcomes of TB/DM including treatment-related complications. Findings will inform the future policies and practices for integrating communicable and NCDs services. ETHICS AND DISSEMINATION Ethical approval was granted by The National Research Health Ethical Committee (Ref-No. NIMR/HQ/R.8a/Vol.IX/2988) and the implementation endorsed by the government authorities. Findings will be proactively disseminated through multiple mechanisms including peer-reviewed journals, and engagement with various stakeholders' example in conferences and social media.
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Affiliation(s)
- Stellah G Mpagama
- Medical, Kibong'oto Infectious Diseases Hospital, Sanya Juu, Tanzania
| | - Kaushik Ramaiya
- Department of Internal Medicine, Shree Hindu Mandal Hospital, Dar es Salaam, Tanzania
| | | | | | | | | | | | - Scott K Heysell
- Division of Infectious Diseases and International Health, University of Virginia, Charlottesville, Virginia, USA
| | - Ib C Bygbjerg
- Global Health Section, Department of Public Health, University of Copenhagen, Copenhagen, Denmark
| | - Dirk L Christensen
- Global Health Section, Department of Public Health, University of Copenhagen, Copenhagen, Denmark
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16
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Liang CN, Zhao HW, Kang J, Hou G, Yin Y. Acute mediastinitis associated with tracheobronchial tuberculosis and aspergillosis: a case report and literature review. J Int Med Res 2021; 48:300060520918469. [PMID: 32431185 PMCID: PMC7241265 DOI: 10.1177/0300060520918469] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022] Open
Abstract
Acute mediastinitis (AM) is a rare but life-threatening disease. Here, we report a case of AM secondary to endobronchial tuberculosis (EBTB) and pseudomembranous Aspergillus tracheobronchitis (PMATB) co-infection. EBTB was confirmed by tissue culture for Mycobacterium tuberculosis and GeneXpert MTB/RIF (Cepheid, Sunnyvale, CA, USA) detection (simultaneous detection of M. tuberculosis and resistance to rifampin) using endobronchial biopsies; PMATB was confirmed by histopathology. Even with antibiotic treatment and systemic support treatment, the patient died of massive hemoptysis on day 10 after admission. When immunocompromised hosts have AM, especially with central airway involvement, EBTB and aspergillosis should be considered potential causes. Bronchoscopy is helpful for rapid diagnosis and administering precise treatment.
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Affiliation(s)
- Chao-Nan Liang
- Department of Pulmonary and Critical Care Medicine, First Hospital of China Medical University, Shenyang, Liaoning, China
| | - Hong-Wen Zhao
- Department of Pulmonary and Critical Care Medicine, First Hospital of China Medical University, Shenyang, Liaoning, China
| | - Jian Kang
- Department of Pulmonary and Critical Care Medicine, First Hospital of China Medical University, Shenyang, Liaoning, China
| | - Gang Hou
- Department of Pulmonary and Critical Care Medicine, First Hospital of China Medical University, Shenyang, Liaoning, China
| | - Yan Yin
- Department of Pulmonary and Critical Care Medicine, First Hospital of China Medical University, Shenyang, Liaoning, China
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17
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Ruslami R, Koesoemadinata RC, Soetedjo NNM, Imaculata S, Gunawan Y, Permana H, Santoso P, Alisjahbana B, McAllister SM, Grint D, Critchley JA, Hill PC, van Crevel R. The effect of a structured clinical algorithm on glycemic control in patients with combined tuberculosis and diabetes in Indonesia: A randomized trial. Diabetes Res Clin Pract 2021; 173:108701. [PMID: 33609618 DOI: 10.1016/j.diabres.2021.108701] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/15/2020] [Revised: 10/05/2020] [Accepted: 02/04/2021] [Indexed: 11/20/2022]
Abstract
AIMS Diabetes mellitus (DM) is associated with worse tuberculosis (TB) treatment outcomes, especially among those with poor glycemic control. We examined whether a structured clinical algorithm could improve glycemic control in TB patients with DM. METHODS In an open label randomized trial, TB-DM patients were randomized to scheduled counselling, glucose monitoring, and adjustment of medication using a structured clinical algorithm (intervention arm) or routine DM management (control arm), with glycated hemoglobin (HbA1c) at month 6 as the primary end point. RESULTS We randomized 150 pulmonary TB-DM patients (92% culture positive, 51.3% male, mean age 53 years). Baseline mean HbA1c was 11.0% in the intervention arm (n = 76) and 11.6% in the control arm (n = 74). At 6 months, HbA1c had decreased more in the intervention arm compared with the control arm (a difference of 1.82% HbA1c, 95% CI 0.82-2.83, p < 0.001). Five patients were hospitalized in the intervention arm and seven in the control arm. There was more hypoglycemia (35.0% vs 11.8%; p = 0.002) in the intervention arm. Two deaths occurred in the intervention arm, one due to cardiorespiratory failure and one because of suspected septic shock and multiorgan failure. CONCLUSION Regular monitoring and algorithmic adjustment of DM treatment led to improved glycemic control.
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Affiliation(s)
- Rovina Ruslami
- Infectious Disease Research Center, Faculty of Medicine, Universitas Padjadjaran, Bandung, Indonesia; Department of Biomedical Science, Faculty of Medicine, Universitas Padjadjaran, Bandung, Indonesia
| | - Raspati C Koesoemadinata
- Infectious Disease Research Center, Faculty of Medicine, Universitas Padjadjaran, Bandung, Indonesia; Department of Internal Medicine, Radboud Institute of Health Sciences, Radboud University Medical Center, Nijmegen, The Netherlands.
| | - Nanny N M Soetedjo
- Infectious Disease Research Center, Faculty of Medicine, Universitas Padjadjaran, Bandung, Indonesia; Department of Internal Medicine, Faculty of Medicine, Universitas Padjadjaran / Hasan Sadikin General Hospital, Bandung, Indonesia
| | - Sofia Imaculata
- Infectious Disease Research Center, Faculty of Medicine, Universitas Padjadjaran, Bandung, Indonesia
| | - Yuanita Gunawan
- Infectious Disease Research Center, Faculty of Medicine, Universitas Padjadjaran, Bandung, Indonesia
| | - Hikmat Permana
- Department of Internal Medicine, Faculty of Medicine, Universitas Padjadjaran / Hasan Sadikin General Hospital, Bandung, Indonesia
| | - Prayudi Santoso
- Infectious Disease Research Center, Faculty of Medicine, Universitas Padjadjaran, Bandung, Indonesia; Department of Internal Medicine, Faculty of Medicine, Universitas Padjadjaran / Hasan Sadikin General Hospital, Bandung, Indonesia
| | - Bachti Alisjahbana
- Infectious Disease Research Center, Faculty of Medicine, Universitas Padjadjaran, Bandung, Indonesia; Department of Internal Medicine, Faculty of Medicine, Universitas Padjadjaran / Hasan Sadikin General Hospital, Bandung, Indonesia
| | - Susan M McAllister
- Centre for International Health, Department of Preventive and Social Medicine, University of Otago Medical School, Dunedin, New Zealand
| | - Daniel Grint
- Tropical Epidemiology Group, London School of Hygiene & Tropical Medicine, London, England, UK
| | - Julia A Critchley
- Population Health Research Institute, St George's University of London, London, England, UK
| | - Philip C Hill
- Centre for International Health, Department of Preventive and Social Medicine, University of Otago Medical School, Dunedin, New Zealand
| | - Reinout van Crevel
- Department of Internal Medicine and Radboud Centre for Infectious Disease (RCI), Radboud University Medical Center, Nijmegen, The Netherlands
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van Crevel R, Critchley JA. The Interaction of Diabetes and Tuberculosis: Translating Research to Policy and Practice. Trop Med Infect Dis 2021; 6:tropicalmed6010008. [PMID: 33435609 PMCID: PMC7838867 DOI: 10.3390/tropicalmed6010008] [Citation(s) in RCA: 35] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2020] [Revised: 12/23/2020] [Accepted: 12/31/2020] [Indexed: 12/17/2022] Open
Abstract
Diabetes Mellitus increases the risk of developing Tuberculosis (TB) disease by about three times; it also doubles the risk of death during TB treatment and other poor TB treatment outcomes. Diabetes may increase the risk of latent infection with Mycobacterium tuberculosis (LTBI), but the magnitude of this effect is less clear. Whilst this syndemic has received considerable attention, most of the published research has focussed on screening for undiagnosed diabetes in TB patients or observational follow-up of TB treatment outcomes by diabetes status. There are thus substantial research and policy gaps, particularly with regard to prevention of TB disease in people with diabetes and management of patients with TB-diabetes, both during TB treatment and after successful completion of TB treatment, when they likely remain at high risk of TB recurrence, mortality from TB and cardiovascular disease. Potential strategies to prevent development of TB disease might include targeted vaccination programmes, screening for LTBI and preventive therapy among diabetes patients or, perhaps ideally, improved diabetes management and prevention. The cost-effectiveness of each of these, and in particular how each strategy might compare with targeted TB prevention among other population groups at higher risk of developing TB disease, is also unknown. Despite research gaps, clinicians urgently need practical management advice and more research evidence on the choice and dose of different anti-diabetes medication and effective medical therapies to reduce cardiovascular risks (statins, anti-hypertensives and aspirin). Substantial health system strengthening and integration may be needed to prevent these at risk patients being lost to care at the end of TB treatment.
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Affiliation(s)
- Reinout van Crevel
- Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, 6500HB Nijmegen, The Netherlands
- Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7LG, UK
- Correspondence:
| | - Julia A. Critchley
- Population Health Research Institute, St George’s, University of London, London SW17 ORE, UK;
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19
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Ugarte-Gil C, Alisjahbana B, Ronacher K, Riza AL, Koesoemadinata RC, Malherbe ST, Cioboata R, Llontop JC, Kleynhans L, Lopez S, Santoso P, Marius C, Villaizan K, Ruslami R, Walzl G, Panduru NM, Dockrell HM, Hill PC, Mc Allister S, Pearson F, Moore DAJ, Critchley JA, van Crevel R. Diabetes Mellitus Among Pulmonary Tuberculosis Patients From 4 Tuberculosis-endemic Countries: The TANDEM Study. Clin Infect Dis 2021; 70:780-788. [PMID: 30958536 DOI: 10.1093/cid/ciz284] [Citation(s) in RCA: 38] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2018] [Accepted: 04/03/2019] [Indexed: 01/15/2023] Open
Abstract
BACKGROUND Diabetes mellitus (DM) increases active tuberculosis (TB) risk and worsens TB outcomes, jeopardizing TB control especially in TB-endemic countries with rising DM prevalence rates. We assessed DM status and clinical correlates in TB patients across settings in Indonesia, Peru, Romania, and South Africa. METHODS Age-adjusted DM prevalence was estimated using laboratory glycated hemoglobin (HbA1c) or fasting plasma glucose in TB patients. Detailed and standardized sociodemographic, anthropometric, and clinical measurements were made. Characteristics of TB patients with or without DM were compared using multilevel mixed-effect regression models with robust standard errors. RESULTS Of 2185 TB patients (median age 36.6 years, 61.2% male, 3.8% human immunodeficiency virus-infected), 12.5% (267/2128) had DM, one third of whom were newly diagnosed. Age-standardized DM prevalence ranged from 10.9% (South Africa) to 19.7% (Indonesia). Median HbA1c in TB-DM patients ranged from 7.4% (Romania) to 11.3% (Indonesia). Compared to those without DM, TB-DM patients were older and had a higher body mass index (BMI) (P value < .05). Compared to those with newly diagnosed DM, TB patients with diagnosed DM had higher BMI and HbA1c, less severe TB, and more frequent comorbidities, DM complications, and hypertension (P value < .05). CONCLUSIONS We show that DM prevalence and clinical characteristics of TB-DM vary across settings. Diabetes is primarily known but untreated, hyperglycemia is often severe, and many patients with TB-DM have significant cardiovascular disease risk and severe TB. This underlines the need to improve strategies for better clinical management of combined TB and DM.
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Affiliation(s)
- Cesar Ugarte-Gil
- School of Medicine, Universidad Peruana Cayetano Heredia, Lima, Perú.,Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.,TB Centre, London School of Hygiene and Tropical Medicine, United Kingdom
| | - Bachti Alisjahbana
- Department of Internal Medicine, Hasan Sadikin Hospital, Bandung, Indonesia.,Infectious Disease Research Center, Faculty of Medicine, Universitas Padjadjaran, Bandung, Indonesia
| | - Katharina Ronacher
- South African Department of Science & Technology and the National Research Foundation Centre of Excellence for Biomedical Tuberculosis Research, South African Medical Research Council Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town.,Translational Research Institute, Mater Research Institute-University of Queensland, Brisbane, Australia
| | - Anca Lelia Riza
- Department of Internal Medicine and Radboud Center of Infectious Diseases, Radboud University Medical Center, Nijmegen, The Netherlands.,Human Genomics Laboratory, University of Medicine and Pharmacy of Craiova, Craiova, Romania.,Regional Centre for Human Genetics-Dolj, Emergency Clinical County Hospital, Craiova, Romania
| | - Raspati C Koesoemadinata
- Infectious Disease Research Center, Faculty of Medicine, Universitas Padjadjaran, Bandung, Indonesia.,Department of Biomedical Sciences, Faculty of Medicine, Universitas Padjadjaran, Bandung, Indonesia
| | - Stephanus T Malherbe
- South African Department of Science & Technology and the National Research Foundation Centre of Excellence for Biomedical Tuberculosis Research, South African Medical Research Council Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town
| | - Ramona Cioboata
- Hospital for Infectious Diseases and Pneumology "Victor Babeș," Craiova, Romania
| | | | - Leanie Kleynhans
- South African Department of Science & Technology and the National Research Foundation Centre of Excellence for Biomedical Tuberculosis Research, South African Medical Research Council Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town
| | - Sonia Lopez
- Laboratorios de Investigación y Desarrollo, Universidad Peruana Cayetano Heredia, Lima, Perú
| | - Prayudi Santoso
- Department of Internal Medicine, Hasan Sadikin Hospital, Bandung, Indonesia.,Infectious Disease Research Center, Faculty of Medicine, Universitas Padjadjaran, Bandung, Indonesia
| | - Ciontea Marius
- Pneumology Hospital Tudor Vladimirescu, Dobrita, jud. Gorj, Bucharest, Romania
| | - Katerine Villaizan
- Laboratorios de Investigación y Desarrollo, Universidad Peruana Cayetano Heredia, Lima, Perú
| | - Rovina Ruslami
- Infectious Disease Research Center, Faculty of Medicine, Universitas Padjadjaran, Bandung, Indonesia.,Department of Biomedical Sciences, Faculty of Medicine, Universitas Padjadjaran, Bandung, Indonesia
| | - Gerhard Walzl
- South African Department of Science & Technology and the National Research Foundation Centre of Excellence for Biomedical Tuberculosis Research, South African Medical Research Council Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town
| | - Nicolae Mircea Panduru
- 2nd Clinical Department, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
| | - Hazel M Dockrell
- Department of Immunology and Infection, London School of Hygiene and Tropical Medicine, United Kingdom
| | - Philip C Hill
- Centre for International Health, University of Otago Medical School, University of Otago, Dunedin, New Zealand
| | - Susan Mc Allister
- Centre for International Health, University of Otago Medical School, University of Otago, Dunedin, New Zealand
| | - Fiona Pearson
- Population Health Research Institute, St Georges, University of London, United Kingdom
| | - David A J Moore
- TB Centre, London School of Hygiene and Tropical Medicine, United Kingdom.,Laboratorios de Investigación y Desarrollo, Universidad Peruana Cayetano Heredia, Lima, Perú
| | - Julia A Critchley
- Population Health Research Institute, St Georges, University of London, United Kingdom
| | - Reinout van Crevel
- Department of Internal Medicine and Radboud Center of Infectious Diseases, Radboud University Medical Center, Nijmegen, The Netherlands
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20
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Molecular detection of Mycobacterium tuberculosis from buccal swabs among adult in Peru. Sci Rep 2020; 10:22231. [PMID: 33335256 PMCID: PMC7746708 DOI: 10.1038/s41598-020-79297-9] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2020] [Accepted: 12/07/2020] [Indexed: 11/18/2022] Open
Abstract
Tuberculosis (TB) diagnosis relies on a sputum sample, which cannot be easily obtained from all symptomatic patients. Mycobacterium tuberculosis DNA can be detected from oral swabs, a noninvasive, safe alternative sample type; however, reported sensitivities have been variable and likely depend on sample collection, processing procedures and host characteristics. We analyzed three buccal swab samples from 123 adults with culture-confirmed TB in Lima, Peru. We compared the sensitivity and specificity of two sample collection devices (OmniSwab and EasiCollect FTA cards) and examined factors associated with detection. DNA was extracted with a commercially available kit and detected via real-time PCR IS6110 amplification. Overall sensitivity for buccal samples was 51% (95% Confidence Interval [CI] 42–60%). Specificity from a single sample among healthy controls was 96.7% (95% CI 83–99.9%). Positive sputum smear and cavitary disease, correlates of disease burden, were associated with detection via buccal swab. Although we observed higher sensitivities with the Omniswab samples, this appeared to be due primarily to differences in patient characteristics (e.g., cavitary disease). Overall, our findings support the potential for a buccal sample-based TB assay. Future work should focus on assay optimization and streamlining the assay workflow.
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21
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Wang W, Du Z, Ni M, Wang Z, Liang M, Sheng H, Zhang A, Yang J. Aspirin enhances the clinical efficacy of anti-tuberculosis therapy in pulmonary tuberculosis in patients with type 2 diabetes mellitus. Infect Dis (Lond) 2020; 52:721-729. [PMID: 32552387 DOI: 10.1080/23744235.2020.1778177] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
Background: Tuberculosis in patients with diabetes mellitus is characterised by rapid disease progression, poor treatment efficacy, poor prognosis and poses a new challenge in tuberculosis treatment and control.Methods: Patients with pulmonary TB and type 2 DM were recruited at Yijishan Hospital of Wannan Medical College. A total of 348 patients were randomly assigned to two groups. The aspirin group (aspirin + TB/DM) included 174 patients who received anti-TB therapy and enteric-coated aspirin tablets (100 mg/tablet). The control group (placebo + TB/DM) included 174 patients who received anti-TB therapy and enteric-coated placebo tablets (an identical tablet containing no drug). Eighty-two patients in the aspirin group and 86 in the control group completed the trial and were included in the analysis. Clinical characteristics, laboratory test results, imaging data and side effects of aspirin were monitored.Results: Aspirin treatment affect certain signs and symptoms. The erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels were lower in the aspirin group than in the control group after treatment (Both p = .000). The sputum-negative conversion rate was 86.7% in the aspirin group, significantly higher than in the control group (53.8%) (p = .031). After two months of treatment, the differences in the number of cases with cavities, the number of cavities, and maximum diameter of cavities in the aspirin group were statistically significant (p = .003, p = .023 and p = .015 respectively).Conclusion: Our findings suggest that aspirin may improve treatment in patients with pulmonary TB and type 2 DM.
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Affiliation(s)
- Wenjie Wang
- Department of Infectious Diseases, Yijishan Hospital of Wannan Medical College, Wuhu, P. R. China
| | - Zhixiang Du
- Department of Infectious Diseases, The People's Hospital of Taizhou, Taizhou, P. R. China
| | - Mingyue Ni
- Department of Infectious Diseases, Yijishan Hospital of Wannan Medical College, Wuhu, P. R. China
| | - Zijian Wang
- Department of Infectious Diseases, Yijishan Hospital of Wannan Medical College, Wuhu, P. R. China
| | - Manman Liang
- Department of Infectious Diseases, Yijishan Hospital of Wannan Medical College, Wuhu, P. R. China
| | - Haoyu Sheng
- Department of Infectious Diseases, Yijishan Hospital of Wannan Medical College, Wuhu, P. R. China
| | - Aiping Zhang
- Department of Infectious Diseases, Yijishan Hospital of Wannan Medical College, Wuhu, P. R. China
| | - Jianghua Yang
- Department of Infectious Diseases, Yijishan Hospital of Wannan Medical College, Wuhu, P. R. China
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22
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Arroyo LH, Yamamura M, Ramos ACV, Campoy LT, Crispim JDA, Berra TZ, Alves LS, Alves YM, Dos Santos FL, Souza LLL, Bruce ATI, de Andrade HLP, Bollela VR, Krainski ET, Nunes C, Arcêncio RA. Determinants of multidrug-resistant tuberculosis in São Paulo-Brazil: a multilevel Bayesian analysis of factors associated with individual, community and access to health services. Trop Med Int Health 2020; 25:839-849. [PMID: 32358845 PMCID: PMC7383622 DOI: 10.1111/tmi.13409] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
Objective Multidrug‐resistant tuberculosis (MDR‐TB) remains a serious public health problem worldwide. Accordingly, this study sought to identify individual, community and access to health services risk factors for MDR‐TB. Methods Retrospective cohort of all TB cases diagnosed between 2006 and 2016 in the state of São Paulo. A Bayesian spatial hierarchical analysis with a multilevel design was carried out. Results It was identified that the history of previous TB treatment (Odds Ratios [OR]:13.86, 95% credibility interval [95% CI]:12.06–15.93), positive sputum culture test (OR: 5.26, 95% CI: 4.44–6.23), diabetes mellitus (OR: 2.34, 95% CI: 1.87–2.91), residing at a standard address (OR: 2.62, 95% CI: 1.91–3.60), positive sputum smear microscopy (OR: 1.74, 95% CI: 1.44–2.12), cavitary pulmonary TB (OR: 1.35, 95% CI: 1.14–1.60) and diagnosis performed due to spontaneous request (OR: 1.26; 95% CI: 1.10–1.46) were associated with MDR‐TB. Furthermore, municipalities that performed HIV tests in less than 42.65% of patients with TB (OR: 1.50, 95% CI: 1.25–1.79), that diagnosed TB cases only after death (OR: 1.50, 95% CI: 1.17–1.93) and that had more than 20.16% of their population with income between ¼ and ½ of one minimum wage (OR: 1.56, 95% CI: 1.30–1.87) were also related to the MDR‐TB. Conclusions Knowledge of these predictive factors may help to develop more comprehensive disease prevention strategies for MDR‐TB, avoiding the risks expressed regarding drug resistance expansion.
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Affiliation(s)
- Luiz Henrique Arroyo
- Ribeirão Preto College of Nursing, University of São Paulo, Ribeirão Preto, Brazil
| | - Mellina Yamamura
- Department of Nursing, Federal University of São Carlos, São Carlos, Brazil
| | | | | | | | - Thais Zamboni Berra
- Ribeirão Preto College of Nursing, University of São Paulo, Ribeirão Preto, Brazil
| | - Luana Seles Alves
- Ribeirão Preto College of Nursing, University of São Paulo, Ribeirão Preto, Brazil
| | - Yan Mathias Alves
- Ribeirão Preto College of Nursing, University of São Paulo, Ribeirão Preto, Brazil
| | | | | | | | | | | | | | - Carla Nunes
- National School of Public Health, Nova University of Lisbon, Lisbon, Portugal
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23
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Ferluga J, Yasmin H, Al-Ahdal MN, Bhakta S, Kishore U. Natural and trained innate immunity against Mycobacterium tuberculosis. Immunobiology 2020; 225:151951. [PMID: 32423788 DOI: 10.1016/j.imbio.2020.151951] [Citation(s) in RCA: 62] [Impact Index Per Article: 12.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2020] [Revised: 04/05/2020] [Accepted: 04/20/2020] [Indexed: 12/14/2022]
Abstract
Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb) infection, remains a major global health emergency. It is estimated that one third of global population are affected, predominantly with latent granuloma form of the disease. Mtb co-evolved with humans, for its obligatory intra-macrophage phagosome habitat and slow replication, balanced against unique mycobacterial innate immunity, which appears to be highly complex. TB is transmitted via cough aerosol Mtb inhalation. Bovine TB attenuated Bacillus Calmette Guerin (BCG) live vaccine has been in practice for protection of young children from severe disseminated Mtb infection, but not sufficiently for their lungs, as obtained by trials in TB endemic community. To augment BCG vaccine-driven innate and adaptive immunity for neonates and better protection against adult pulmonary TB, a number of BCG pre-vaccination based, subset vaccine candidates have been tested via animal preclinical, followed by safe clinical trials. BCG also enhances innate macrophage trained immunity and memory, through primordial intracellular Toll-like receptors (TLRs) 7 and 9, which recognise distinct mycobacterial molecular pattern signature. This signature is transmitted by TLR signalling via nuclear factor-κB, for activating innate immune transcription and expression of gene profiling in a mycobacterial signature-specific manner. These are epigenetically imprinted in reprogramming of distinct chromatin areas for innate immune memory, to be recalled following lung reinfection. Unique TB innate immunity and its trained memory are considered independent from adaptive immune B and T cells. On the other hand, adaptive immunity is crucial in Mtb containment in granulomatous latency, supported by innate immune cell infiltration. In nearly 5-10 % of susceptible people, latent TB may be activated due to immune evasion by Mtb from intracellular phagosome within macrophage, perpetrating TB. However, BCG and new recombinant BCG vaccines have the capacity, as indicated in pre- and clinical trials, to overcome such Mtb evasion. Various strategies include pro-inflammatory-bactericidal type 1 polarisation (M1) phenotype of the infected macrophage, involving thrombospondin-TLR pathway. Saprophytic M. smegmatis-based recombinant vaccines are also promising candidates against TB. BCG vaccination of neonates/infants in TB endemic countries also reduced their pneumonia caused by various microbes independent of TB immunity. Here, we discuss host immune response against Mtb, its immune evasion strategies, and the important role innate immunity plays in the development of protection against TB.
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Affiliation(s)
- Janez Ferluga
- Biosciences, College of Health and Life Sciences, Brunel University London, Uxbridge UB8 3PH, United Kingdom
| | - Hadida Yasmin
- Immunology and Cell Biology Laboratory, Department of Zoology, Cooch Behar Panchanan Barma University, Cooch Behar, West Bengal, India
| | - Mohammed N Al-Ahdal
- Department of Infection and Immunity, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia
| | - Sanjib Bhakta
- Institute of Structural and Molecular Biology, Department of Biological Sciences, Birkbeck, University of London, London WC1E 7HX, United Kingdom
| | - Uday Kishore
- Biosciences, College of Health and Life Sciences, Brunel University London, Uxbridge UB8 3PH, United Kingdom.
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Lakoh S, Jiba DF, Adekanmbi O, Poveda E, Sahr F, Deen GF, Foray LM, Gashau W, Hoffmann CJ, Salata RA, Yendewa GA. Diagnosis and treatment outcomes of adult tuberculosis in an urban setting with high HIV prevalence in Sierra Leone: A retrospective study. Int J Infect Dis 2020; 96:112-118. [PMID: 32339724 DOI: 10.1016/j.ijid.2020.04.038] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2020] [Revised: 04/15/2020] [Accepted: 04/17/2020] [Indexed: 12/21/2022] Open
Abstract
OBJECTIVE To assess the diagnosis, treatment outcomes, and predictors of mortality in adult tuberculosis (TB) patients in an urban setting with a high HIV prevalence. METHODS A retrospective study was conducted of adult TB patients aged ≥15 years who were treated at Connaught Hospital in Freetown, Sierra Leone from January through December 2017. Multivariate logistic regression was used to identify predictors of mortality. RESULTS Of 1127 TB cases notified in 2017, 1105 (98%) were tested for HIV, yielding a TB/HIV co-infection rate of 32.0%. Only HIV-tested cases (n=1105) were included in the final analysis. The majority were male (69.3%), aged 25-34 years (29.2%), and had pulmonary TB (96.3%). Treatment outcomes were as follows: 29.0% cured, 29.0% completed, 0.5% treatment failure, 24.2% lost to follow-up, 12.8% transferred/not evaluated, and 4.5% died. The majority of deaths (80.0%, 40/50) occurred within 2 months of TB treatment initiation. Age 65 years or older (adjusted odds ratio 3.48, 95% confidence interval 1.15-10.56; p=0.027) and HIV-positive status (adjusted odds ratio 3.50, 95% confidence interval 1.72-7.12; p=0.001) were independent predictors of mortality. CONCLUSIONS Suboptimal TB treatment outcomes were observed in Sierra Leone in 2017. More local and international action is warranted to help achieve the 2035 global TB elimination targets.
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Affiliation(s)
- Sulaiman Lakoh
- College of Medicine and Allied Health Sciences, University of Sierra Leone, Freetown, Sierra Leone; Department of Medicine, University of Sierra Leone Teaching Hospitals Complex, Freetown, Sierra Leone.
| | - Darlinda F Jiba
- Department of Medicine, University of Sierra Leone Teaching Hospitals Complex, Freetown, Sierra Leone
| | - Olukemi Adekanmbi
- College of Medicine, University of Ibadan, Ibadan, Nigeria; Department of Medicine, University College Hospital, Ibadan, Nigeria
| | - Eva Poveda
- Group of Virology and Pathogenesis, Galicia Sur Health Research Institute, Complexo Hospitalario Universitario de Vigo, SERGAS-Vigo, Vigo, Spain
| | - Foday Sahr
- College of Medicine and Allied Health Sciences, University of Sierra Leone, Freetown, Sierra Leone
| | - Gibrilla F Deen
- College of Medicine and Allied Health Sciences, University of Sierra Leone, Freetown, Sierra Leone; Department of Medicine, University of Sierra Leone Teaching Hospitals Complex, Freetown, Sierra Leone
| | - Lynda M Foray
- National TB and Leprosy Control Programme, Ministry of Health and Sanitation, Government of Sierra Leone, Freetown, Sierra Leone
| | - Wadzani Gashau
- College of Medical Sciences, University of Maiduguri, Maiduguri, Nigeria
| | | | - Robert A Salata
- Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA; Division of Infectious Diseases and HIV Medicine, University Hospitals Cleveland Medical Center, Cleveland, Ohio, USA
| | - George A Yendewa
- Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA; Division of Infectious Diseases and HIV Medicine, University Hospitals Cleveland Medical Center, Cleveland, Ohio, USA; Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA
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White LV, Edwards T, Lee N, Castro MC, Saludar NR, Calapis RW, Faguer BN, Fuente ND, Mayoga F, Saito N, Ariyoshi K, Garfin AMCG, Solon JA, Cox SE. Patterns and predictors of co-morbidities in Tuberculosis: A cross-sectional study in the Philippines. Sci Rep 2020; 10:4100. [PMID: 32139742 PMCID: PMC7058028 DOI: 10.1038/s41598-020-60942-2] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2019] [Accepted: 02/19/2020] [Indexed: 12/22/2022] Open
Abstract
Diabetes and undernutrition are common risk factors for TB, associated with poor treatment outcomes and exacerbated by TB. We aimed to assess non-communicable multimorbidity (co-occurrence of two or more medical conditions) in Filipino TB outpatients, focusing on malnutrition and diabetes. In a cross-sectional study, 637 adults (70% male) from clinics in urban Metro Manila (N = 338) and rural Negros Occidental (N = 299) were enrolled. Diabetes was defined as HbA1c of ≥6.5% and/or current diabetes medication. Study-specific HIV screening was conducted. The prevalence of diabetes was 9.2% (54/589, 95%CI: 7.0-11.8%) with 52% newly diagnosed. Moderate/severe undernutrition (body mass index (BMI) <17 kg/2) was 20.5% (130/634, 95%CI: 17.4-23.9%). Forty percent of participants had at least one co-morbidity (diabetes, moderate/severe undernutrition or moderate/severe anaemia (haemoglobin <11 g/dL)). HIV infection (24.4%, 74/303) was not associated with other co-morbidities (but high refusal in rural clinics). Central obesity assessed by waist-to-hip ratio was more strongly associated with diabetes (Adjusted Odds Ratio (AOR) = 6.16, 95%CI: 3.15-12.0) than BMI. Undernutrition was less common in men (AOR = 0.44, 95%CI: 0.28-0.70), and associated with previous history of TB (AOR = 1.97, 95%CI: 1.28-3.04) and recent reduced food intake. The prevalence of multimorbidity was high demonstrating a significant unmet need. HIV was not a risk factor for increased non-communicable multimorbidity.
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Affiliation(s)
- Laura V White
- School of Tropical Medicine and Global Health, Nagasaki University, Nagasaki, Japan
| | - Tansy Edwards
- School of Tropical Medicine and Global Health, Nagasaki University, Nagasaki, Japan
- Tropical Epidemiology Group, London School of Hygiene and Tropical Medicine, London, UK
| | - Nathaniel Lee
- School of Tropical Medicine and Global Health, Nagasaki University, Nagasaki, Japan
- Royal Free Hospital, London, UK
| | - Mary C Castro
- Nutrition Center Philippines, Manila, The Philippines
| | | | | | - Benjamin N Faguer
- School of Tropical Medicine and Global Health, Nagasaki University, Nagasaki, Japan
| | - Nelson Dela Fuente
- Valladolid Health Center, Valladolid, Negros Occidental, The Philippines
| | - Ferdinand Mayoga
- Bago City Health Center, Bago City, Negros Occidental, The Philippines
| | - Nobuo Saito
- Institute of Tropical Medicine, Nagasaki University, Nagasaki, Japan
| | - Koya Ariyoshi
- Institute of Tropical Medicine, Nagasaki University, Nagasaki, Japan
| | | | - Juan A Solon
- Nutrition Center Philippines, Manila, The Philippines
| | - Sharon E Cox
- School of Tropical Medicine and Global Health, Nagasaki University, Nagasaki, Japan.
- Institute of Tropical Medicine, Nagasaki University, Nagasaki, Japan.
- Faculty of Population Health, London School of Hygiene and Tropical Medicine, London, UK.
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Chakaya JM, Harries AD, Marks GB. Ending tuberculosis by 2030-Pipe dream or reality? Int J Infect Dis 2020; 92S:S51-S54. [PMID: 32114202 DOI: 10.1016/j.ijid.2020.02.021] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2020] [Revised: 02/12/2020] [Accepted: 02/12/2020] [Indexed: 01/15/2023] Open
Abstract
Tuberculosis (TB) remains a major public health threat. In 2018, an estimated 10 million people fell ill with TB and 1.5 million died of the disease. The End TB Strategy envisages an end to TB as a public health threat and has set ambitious targets to reduce TB incidence and mortality by 90% and 95%, respectively, by 2035 compared with 2015. In this paper we describe the progress that is being made towards the achievement of these targets and highlight the challenges that are hampering this progress. The development and deployment of new tools will certainly accelerate progress towards ending TB. We believe that the end of TB is realizable if there are sustained efforts to actively find TB cases, a more robust multi-sectoral approach to tackle social determinants of TB, and improved person-centred health services.
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Affiliation(s)
- Jeremiah M Chakaya
- International Union Against Tuberculosis and Lung Disease, Paris, France; Department of Medicine, Therapeutics, Dermatology and Psychiatry, Kenyatta University, Nairobi, Kenya.
| | - Anthony D Harries
- International Union Against Tuberculosis and Lung Disease, Paris, France; Department of Clinical Research, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK
| | - Guy B Marks
- International Union Against Tuberculosis and Lung Disease, Paris, France; Woolcock Institute of Medical Research, Sydney, Australia; University of New South Wales, Sydney, Australia
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Zhang HQ, Liao W, Wang YX. Response to "Comment on Wang et al.: One-stage posterior focus debridement, interbody graft using titanium mesh cages, posterior instrumentation and fusion in the surgical treatment of lumbo-sacral spinal tuberculosis in the aged". INTERNATIONAL ORTHOPAEDICS 2019; 44:195-196. [PMID: 31478070 DOI: 10.1007/s00264-019-04407-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/12/2019] [Accepted: 08/27/2019] [Indexed: 10/26/2022]
Affiliation(s)
- Hong-Qi Zhang
- Department of Spine Surgery, Xiangya Spinal Surgery Center, Xiangya Hospital of Central South University, Xiang Ya Road 87, ChangSha, China.,National Clinical Research Center for Geriatric Disorder, Xiangya Hospital of Central South University, ChangSha, China
| | - Weiwei Liao
- Department of Health Management Center, Xiangya Hospital of Central South University, ChangSha, China
| | - Yu-Xiang Wang
- Department of Spine Surgery, Xiangya Spinal Surgery Center, Xiangya Hospital of Central South University, Xiang Ya Road 87, ChangSha, China. .,National Clinical Research Center for Geriatric Disorder, Xiangya Hospital of Central South University, ChangSha, China.
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Oglesby W, Kara AM, Granados H, Cervantes JL. Metformin in tuberculosis: beyond control of hyperglycemia. Infection 2019; 47:697-702. [PMID: 31119504 DOI: 10.1007/s15010-019-01322-5] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2019] [Accepted: 05/14/2019] [Indexed: 10/26/2022]
Abstract
Two global epidemics, diabetes mellitus (DM) and tuberculosis (TB), have converged making their control even more challenging. We herein have reviewed metformin's (MTF) effect on patients with active and latent TB, as well as discussed its newly discovered biological mechanisms in mycobacteria. Mounting evidence suggests that MTF provides better outcomes in TB patients, especially those with DM. The mechanisms by which MTF produces its benefits are multiple. Though metformin's potential has been proven in patients with DM, larger and more thorough clinical trials, in DM and non-DM-TB patients, need to be conducted. MTF could be added to the arsenal of anti-TB drugs, aiding in the goal of TB eradication worldwide.
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Affiliation(s)
- William Oglesby
- Department of Medical Education, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso, 5001 El Paso Dr., El Paso, TX, 79905, USA
| | - Ali M Kara
- Department of Medical Education, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso, 5001 El Paso Dr., El Paso, TX, 79905, USA
| | - Hector Granados
- Department of Pediatrics, Texas Tech University Health Sciences Center, El Paso, El Paso, TX, 79905, USA
| | - Jorge L Cervantes
- Department of Medical Education, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso, 5001 El Paso Dr., El Paso, TX, 79905, USA.
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