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Getaneh Y, Dejene Y, Adankie BT, Khairunisa SQ, Husada D, Kuntaman K, Lusida MI. Exploring survival rates in HIV-infected Ethiopian children receiving HAART: a retrospective cohort study. BMJ Paediatr Open 2025; 9:e003022. [PMID: 39824536 PMCID: PMC11749865 DOI: 10.1136/bmjpo-2024-003022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/13/2024] [Accepted: 12/30/2024] [Indexed: 01/20/2025] Open
Abstract
BACKGROUND Studies have shown a high rate of mortality among adults despite the introduction of highly active antiretroviral therapy (HAART). However, long-term outcomes of HAART among children remain poorly documented in Ethiopia. This study aimed to estimate the survival rate and identify associated factors among HIV-infected children on antiretroviral therapy. METHODS A retrospective cohort study was conducted from August to December 2022 in 13 health facilities (HFs) using records of 554 children (<15 years old) initiating HAART from 2007 to 2019. HFs were selected using probability proportional to the size of patients. Survival rate and predictors of mortality were estimated using Kaplan-Meier and Cox-proportional hazards, respectively. The analysis was done using STATA V.16.0. RESULT Overall mortality among HIV-positive children taking HAART in Ethiopia in 12-year follow-up was 25.5%. Moreover, the mortality rate was 24 per 100 child-year observation. Survival during the median 9.65 (95% CI=9.30 to 10.00) years of follow-up was 0.50. There was a significant drop in the survival rate from the 6th year of follow-up (0.96) to the 8th year (0.78) till the 12th year (0.18). By the end of the follow-up period, 172 (23.69%) were lost to follow-up. There was a high risk of mortality among female (adjusted HRs (AHRs) (95% CI) =1.35 (1.14 to 1.65)), those with poor adherence (AHR (95% CI) =1.29 (1.13 to 1.35)), CD4 count of ≤200 cells/mm3 (AHR (95% CI) =1.75 (1.33 to 2.30)) and baseline haemoglobin≤12 g/dL (AHR (95% CI) =1.8 (1.66 to 1.98)). CONCLUSION The significant drop in the survival rate as of the 6th year follow-up and the high loss rate to follow-up call for programme attention. Close follow-up of children with low CD4 count, low haemoglobin and poor adherence could help improve survival.
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Affiliation(s)
- Yimam Getaneh
- Doctoral Program, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia
- Infectious Disease Research Directorate, Ethiopian Public health Institute, Addis Ababa, Ethiopia
- Research Center on Global Emerging and Re-emerging Infectious Diseases, Institute of Tropical Disease, Universitas Airlangga, Surabaya, 60115, Indonesia
| | - Yared Dejene
- St. Paul Hospital Millennium Medical College, Addis Ababa, Ethiopia
| | | | - Siti Qamariyah Khairunisa
- Research Center on Global Emerging and Re-emerging Infectious Diseases, Institute of Tropical Disease, Universitas Airlangga, Surabaya, 60115, Indonesia
- Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia
| | | | | | - Maria Inge Lusida
- Research Center on Global Emerging and Re-emerging Infectious Diseases, Institute of Tropical Disease, Universitas Airlangga, Surabaya, 60115, Indonesia
- Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia
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Brumec M, Sobočan M, Takač I, Arko D. Clinical Implications of Androgen-Positive Triple-Negative Breast Cancer. Cancers (Basel) 2021; 13:1642. [PMID: 33915941 PMCID: PMC8037213 DOI: 10.3390/cancers13071642] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2021] [Revised: 03/18/2021] [Accepted: 03/26/2021] [Indexed: 12/22/2022] Open
Abstract
This review summarizes the recent findings of a vast array of studies conducted on androgen receptor-positive triple-negative breast cancer (AR-positive TNBC) to provide a better understanding of this specific breast cancer subgroup. AR expression is correlated with higher age, lower histological grade, lower proliferation index Ki-67, spiculated masses, and calcifications on mammography. Studies investigating the correlation between AR expression and lymph node metastasis are highly discordant. In addition, results regarding prognosis are highly contradictory. AR antagonists are a promising novel therapeutic approach in AR-positive TNBC. However, AR signaling pathways should be more investigated in order to understand the influence of AR expression on TNBC more thoroughly.
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Affiliation(s)
- Maša Brumec
- Department of Obstetrics and Gynecology, Faculty of Medicine, University of Maribor, 2000 Maribor, Slovenia; (M.B.); (I.T.); (D.A.)
| | - Monika Sobočan
- Department of Obstetrics and Gynecology, Faculty of Medicine, University of Maribor, 2000 Maribor, Slovenia; (M.B.); (I.T.); (D.A.)
- Department of Pharmacology, Faculty of Medicine, University of Maribor, 2000 Maribor, Slovenia
- Divison of Gynecology and Perinatology, University Medical Centre Maribor, 2000 Maribor, Slovenia
| | - Iztok Takač
- Department of Obstetrics and Gynecology, Faculty of Medicine, University of Maribor, 2000 Maribor, Slovenia; (M.B.); (I.T.); (D.A.)
- Divison of Gynecology and Perinatology, University Medical Centre Maribor, 2000 Maribor, Slovenia
| | - Darja Arko
- Department of Obstetrics and Gynecology, Faculty of Medicine, University of Maribor, 2000 Maribor, Slovenia; (M.B.); (I.T.); (D.A.)
- Divison of Gynecology and Perinatology, University Medical Centre Maribor, 2000 Maribor, Slovenia
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Sabir N, Hussain T, Mangi MH, Zhao D, Zhou X. Matrix metalloproteinases: Expression, regulation and role in the immunopathology of tuberculosis. Cell Prolif 2019; 52:e12649. [PMID: 31199047 PMCID: PMC6668971 DOI: 10.1111/cpr.12649] [Citation(s) in RCA: 42] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2019] [Revised: 05/11/2019] [Accepted: 05/15/2019] [Indexed: 12/25/2022] Open
Abstract
Mycobacterium tuberculosis (Mtb) leads to approximately 1.5 million human deaths every year. In pulmonary tuberculosis (TB), Mtb must drive host tissue destruction to cause pulmonary cavitation and dissemination in the tissues. Matrix metalloproteinases (MMPs) are endopeptidases capable of degrading all components of pulmonary extracellular matrix (ECM). It is well established that Mtb infection leads to upregulation of MMPs and also causes disturbance in the balance between MMPs and tissue inhibitors of metalloproteinases (TIMPs), thus altering the extracellular matrix deposition. In TB, secretion of MMPs is mainly regulated by NF-κB, p38 and MAPK signalling pathways. In addition, recent studies have demonstrated the immunomodulatory roles of MMPs in Mtb pathogenesis. Researchers have proposed a new regimen of improved TB treatment by inhibition of MMP activity to hinder matrix destruction and to minimize the TB-associated morbidity and mortality. The proposed regimen involves adjunctive use of MMP inhibitors such as doxycycline, marimastat and other related drugs along with front-line anti-TB drugs to reduce granuloma formation and bacterial load. These findings implicate the possible addition of economical and well-tolerated MMP inhibitors to current multidrug regimens as an attractive mean to increase the drug potency. Here, we will summarize the recent advancements regarding expression of MMPs in TB, their immunomodulatory role, as well as their potential as therapeutic targets to control the deadly disease.
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Affiliation(s)
- Naveed Sabir
- Key Laboratory of Animal Epidemiology and Zoonosis, Ministry of Agriculture, National Animal Transmissible Spongiform Encephalopathy Laboratory, College of Veterinary MedicineChina Agricultural UniversityBeijingChina
| | - Tariq Hussain
- Key Laboratory of Animal Epidemiology and Zoonosis, Ministry of Agriculture, National Animal Transmissible Spongiform Encephalopathy Laboratory, College of Veterinary MedicineChina Agricultural UniversityBeijingChina
| | - Mazhar Hussain Mangi
- Key Laboratory of Animal Epidemiology and Zoonosis, Ministry of Agriculture, National Animal Transmissible Spongiform Encephalopathy Laboratory, College of Veterinary MedicineChina Agricultural UniversityBeijingChina
| | - Deming Zhao
- Key Laboratory of Animal Epidemiology and Zoonosis, Ministry of Agriculture, National Animal Transmissible Spongiform Encephalopathy Laboratory, College of Veterinary MedicineChina Agricultural UniversityBeijingChina
| | - Xiangmei Zhou
- Key Laboratory of Animal Epidemiology and Zoonosis, Ministry of Agriculture, National Animal Transmissible Spongiform Encephalopathy Laboratory, College of Veterinary MedicineChina Agricultural UniversityBeijingChina
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Chen J, Cao W, Chen R, Ren Y, Li T. Prevalence and determinants of HIV in tuberculosis patients in Wuxi City, Jiangsu province, China: a cross-sectional study. Int J STD AIDS 2015; 27:1204-1212. [PMID: 26482328 DOI: 10.1177/0956462415612618] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2015] [Accepted: 09/21/2015] [Indexed: 10/22/2022]
Abstract
At least one-third of the 34 million people living with human immunodeficiency virus (HIV) worldwide are infected with latent tuberculosis (TB). The aim of this study was to determine the rate of HIV infection in TB patients and its determinants in Wuxi City, China. TB patients attending health institutions (12 selected sites) for TB diagnosis and treatment were enrolled in this study. TB diagnosis, treatment and HIV testing were done according to the national guidelines. Blood samples were collected for anonymous HIV testing. Among the TB patients, the HIV prevalence was 13.66% (1493/10,926). Multivariate analysis showed that gender, age, education, marital status, per capita monthly income, patient residence, family size, distance from a health institution, knowledge of HIV-TB co-infection, and knowledge of HIV may be risk factors for HIV-TB co-infection (all: odds ratio > 1, p < 0.05). The prevalence of TB in those with HIV was higher among the study participants. Improving public awareness of HIV-TB co-infection, regularly screening and improving follow-up can reduce the occurrence of HIV-TB co-infection.
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Affiliation(s)
- Judi Chen
- Department of Nursing, Wuxi No.5 People's Hospital, Wuxi, Jiangsu, P.R. China
| | - Weining Cao
- Department of Tuberculosis, Wuxi No.5 People's Hospital, Wuxi, Jiangsu, P.R. China
| | - Renfang Chen
- Department of Infectious Diseases, Wuxi No.5 People's Hospital, Wuxi, Jiangsu, P.R. China
| | - Yong Ren
- Department of Red ribbon Care Center, Wuxi No.5 People's Hospital, Wuxi, Jiangsu, P.R. China
| | - Tao Li
- Department of Medical affairs, the Lixin People's Hospital, Bozhou, Anhui, P.R. China
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Espert L, Beaumelle B, Vergne I. Autophagy in Mycobacterium tuberculosis and HIV infections. Front Cell Infect Microbiol 2015; 5:49. [PMID: 26082897 PMCID: PMC4451423 DOI: 10.3389/fcimb.2015.00049] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2015] [Accepted: 05/18/2015] [Indexed: 12/31/2022] Open
Abstract
Human Immunodeficiency Virus (HIV) and Mycobacterium tuberculosis (M.tb) are among the most lethal human pathogens worldwide, each being responsible for around 1.5 million deaths annually. Moreover, synergy between acquired immune deficiency syndrome (AIDS) and tuberculosis (TB) has turned HIV/M.tb co-infection into a major public health threat in developing countries. In the past decade, autophagy, a lysosomal catabolic process, has emerged as a major host immune defense mechanism against infectious agents like M.tb and HIV. Nevertheless, in some instances, autophagy machinery appears to be instrumental for HIV infection. Finally, there is mounting evidence that both pathogens deploy various countermeasures to thwart autophagy. This mini-review proposes an overview of the roles and regulations of autophagy in HIV and M.tb infections with an emphasis on microbial factors. We also discuss the role of autophagy manipulation in the context of HIV/M.tb co-infection. In future, a comprehensive understanding of autophagy interaction with these pathogens will be critical for development of autophagy-based prophylactic and therapeutic interventions for AIDS and TB.
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Affiliation(s)
- Lucile Espert
- CPBS FRE 3689 Centre National de la Recherche Scientifique, UM Montpellier, France
| | - Bruno Beaumelle
- CPBS FRE 3689 Centre National de la Recherche Scientifique, UM Montpellier, France
| | - Isabelle Vergne
- Institut de Pharmacologie et de Biologie Structurale, UMR 5089 Centre National de la Recherche Scientifique - Université de Toulouse Toulouse, France
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Mthiyane T, Rustomjee R, Pym A, Connolly C, Onyebujoh P, Theron G, Dheda K. Impact of tuberculosis treatment and antiretroviral therapy on serial RD-1-specific quantitative T-cell readouts (QuantiFERON-TB Gold In-Tube), and relationship to treatment-related outcomes and bacterial burden. Int J Infect Dis 2015; 36:46-53. [PMID: 26003404 DOI: 10.1016/j.ijid.2015.05.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2015] [Revised: 05/04/2015] [Accepted: 05/05/2015] [Indexed: 10/23/2022] Open
Abstract
BACKGROUND The impact of anti-tuberculosis treatment with and without antiretroviral therapy (ART) on standardized interferon gamma release assay (IGRA) readouts has been studied inadequately in high-burden countries. METHODS The QuantiFERON-TB Gold In-Tube (QFT-GIT) test was used to evaluate interferon gamma (IFN-γ) responses longitudinally (0, 3, 6, and 12 months post initiation of tuberculosis (TB)-HIV co-treatment or ART alone) in 82 HIV-infected patients. RESULTS Of the 65 evaluable participants, 30 were co-infected on ART, 17 were co-infected but not on ART, and 18 were HIV-infected alone and on ART. In HIV-infected and HIV-TB-infected patients on ART, IFN-γ responses increased, whilst they decreased in those not on ART. However, baseline, month 3, and month 6 IFN-γ responses, irrespective of ART, did not differ in TB-HIV co-infected patients who culture-converted compared to those who did not (1.25 vs. 1.05, p=0.5 at baseline; 3.76 vs. 1.15, p=0.2 for month 3; 0.06 vs. 0.7, p=0.3 for month 6). IFN-γ levels did not correlate with the magnitude of sputum bacillary load, smear status, or liquid culture time-to-positivity. CONCLUSION As IGRAs do not correlate with 2- or 6-month culture conversion or with markers of bacillary burden, they are unlikely to be useful for the prognostication of treatment outcome in co-infected patients.
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Affiliation(s)
- Thuli Mthiyane
- South African Medical Research Council, Parow Valley, Cape Town, South Africa
| | - Roxana Rustomjee
- South African Medical Research Council, Parow Valley, Cape Town, South Africa
| | - Alex Pym
- KwaZulu-Natal Research Institute for Tuberculosis and HIV (K-RITH), Nelson Mandela School of Medicine, Durban, South Africa
| | - Cathy Connolly
- South African Medical Research Council, Biostatistics Department, Durban, South Africa
| | - Philip Onyebujoh
- World Health Organization/Special Programme for Research and Training in Tropical diseases (TDR), Geneva, Switzerland
| | - Grant Theron
- Lung Infection and Immunity Unit, Division of Pulmonology, Department of Medicine, University of Cape Town, J flr, Old Main Bldg, Groote Schuur Hospital, Observatory, Cape Town, 7925, South Africa
| | - Keertan Dheda
- Lung Infection and Immunity Unit, Division of Pulmonology, Department of Medicine, University of Cape Town, J flr, Old Main Bldg, Groote Schuur Hospital, Observatory, Cape Town, 7925, South Africa.
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Ofoegbu OS, Odume BB. Treatment outcome of tuberculosis patients at National Hospital Abuja Nigeria: a five year retrospective study. S Afr Fam Pract (2004) 2015. [DOI: 10.1080/20786190.2014.995913] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/24/2022] Open
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Mycobacterium tuberculosis-specific TNF-α is a potential biomarker for the rapid diagnosis of active tuberculosis disease in Chinese population. PLoS One 2013; 8:e79431. [PMID: 24244502 PMCID: PMC3823617 DOI: 10.1371/journal.pone.0079431] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2013] [Accepted: 10/01/2013] [Indexed: 11/19/2022] Open
Abstract
Interferon-gamma release assays (IGRAs) have proven to be useful to accurately detect Mycobacterium tuberculosis (Mtb) infection, but they cannot reliably discriminate between active tuberculosis (TB) and latent tuberculosis infection (LTBI). This study aims to test whether Mtb-specific tumor necrosis factor-alpha (TNF-α) could be used as a new tool for the rapid diagnosis of active TB disease. The secretion of TNF-α by Mtb-specific antigen-stimulated peripheral blood mononuclear cells (PBMCs) of sixty seven participants was investigated in the study. Our results showed that the total measurement of TNF-α secretion by Mtb-specific antigen-stimulated PBMCs is not a good biomarker for active TB diagnosis. However, we found that calculation of Mtb-specific TNF-α not only distinguish between active and latent TB infection, but also can differentiate active TB from non-TB patients. Using the cutoff value of 136.9 pg/ml for Mtb-specific TNF-α, we were able to differentiate active TB from LTBI. Sensitivity and specificity were 72% and 90.91%. These data suggest that Mtb-specific TNF-α could be a potential biomarker for the diagnosis of active TB disease.
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Brust JCM, Berman AR, Zalta B, Haramati LB, Ning Y, Heo M, van der Merwe TL, Bamber S, Moll AP, Friedland GH, Shah NS, Gandhi NR. Chest radiograph findings and time to culture conversion in patients with multidrug-resistant tuberculosis and HIV in Tugela Ferry, South Africa. PLoS One 2013; 8:e73975. [PMID: 24040132 PMCID: PMC3765317 DOI: 10.1371/journal.pone.0073975] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2013] [Accepted: 07/26/2013] [Indexed: 01/16/2023] Open
Abstract
Background The majority of patients with multidrug-resistant tuberculosis (MDR-TB) in South Africa are co-infected with HIV, but the radiographic features of MDR-TB and their relationship with time to sputum culture conversion in the antiretroviral therapy era have not been described. Methods We reviewed baseline chest radiographs for 56 patients with MDR-TB from a rural area of South Africa. We analyzed the association of cavities, consolidation, pleural effusion and hilar lymphadenopathy with time to sputum culture conversion, adjusting for HIV status, baseline sputum smear and CD4 count. Results Of the 56 subjects, 49 (88%) were HIV-positive, with a median CD4 count of 136 cells/mm3 (IQR 65-249). Thirty-two (57%) patients were sputum smear positive. Twenty-two (39%) patients had a cavity and 37 (66%) patients had consolidations. Cavitary disease and consolidations were each associated with longer time to culture conversion on bivariate analysis but not after adjusting for sputum smear status (aORs 1.79 [0.94-3.42] and 1.09 [0.67-1.78], respectively). Positive baseline sputum smear remained independently associated with longer time to conversion (aOR 3.45 [1.39-8.59]). We found no association between pleural effusion or hilar lymphadenopathy and time to conversion. Seventy-nine percent of patients were cured at the end of treatment. Conclusions Despite high rates of HIV co-infection and advanced immunodeficiency, the majority of patients had severe pathology on baseline chest radiograph. Nevertheless, culture conversion rates were high and treatment outcomes were favorable. Cavitation and consolidation do not appear to have an independent association with time to culture conversion beyond that of baseline sputum smear status.
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Affiliation(s)
- James C. M. Brust
- Albert Einstein College of Medicine & Montefiore Medical Center, Bronx, New York, United States of America
- * E-mail:
| | - Andrew R. Berman
- Albert Einstein College of Medicine & Montefiore Medical Center, Bronx, New York, United States of America
- New Jersey Medical School, Newark, New Jersey, United States of America
| | - Benjamin Zalta
- Albert Einstein College of Medicine & Montefiore Medical Center, Bronx, New York, United States of America
| | - Linda B. Haramati
- Albert Einstein College of Medicine & Montefiore Medical Center, Bronx, New York, United States of America
| | - Yuming Ning
- Albert Einstein College of Medicine & Montefiore Medical Center, Bronx, New York, United States of America
| | - Moonseong Heo
- Albert Einstein College of Medicine & Montefiore Medical Center, Bronx, New York, United States of America
| | | | - Sheila Bamber
- Philanjalo and Church of Scotland Hospital, Tugela Ferry, South Africa
- Centre for the AIDS Programme of Research in South Africa (CAPRISA), Durban, South Africa
| | - Anthony P. Moll
- Philanjalo and Church of Scotland Hospital, Tugela Ferry, South Africa
| | - Gerald H. Friedland
- Yale University School of Medicine, New Haven, Connecticut, United States of America
| | - N. Sarita Shah
- Albert Einstein College of Medicine & Montefiore Medical Center, Bronx, New York, United States of America
| | - Neel R. Gandhi
- Albert Einstein College of Medicine & Montefiore Medical Center, Bronx, New York, United States of America
- Emory University Rollins School of Public Health, Atlanta, Georgia, United States of America
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Sun D, Dorman S, Shah M, Manabe YC, Moodley VM, Nicol MP, Dowdy DW. Cost utility of lateral-flow urine lipoarabinomannan for tuberculosis diagnosis in HIV-infected African adults. Int J Tuberc Lung Dis 2013; 17:552-8. [PMID: 23485389 DOI: 10.5588/ijtld.12.0627] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023] Open
Abstract
SETTING In-patient hospitals in South Africa and Uganda. OBJECTIVE To evaluate the cost-effectiveness of a lateral-flow urine lipoarabinomannan (LAM) test when added to existing strategies for tuberculosis (TB) diagnosis in human immunodeficiency virus infected adults (CD4(+) T-cell counts < 100 cells/l) with symptoms of active TB. DESIGN Decision-analytic cost-utility model, with the primary outcome being the incremental cost-effectiveness ratio, expressed in 2010 US dollars per disability-adjusted life year (DALY) averted from the perspective of a public sector TB control program. RESULTS AND CONCLUSION For every 1000 patients tested, adding lateral-flow urine LAM generated 80 incremental appropriate anti-tuberculosis treatments and averted 224 DALYs. Estimated cost utility was US$353 per DALY averted (95% uncertainty range $192$1161) in South Africa and $86 per DALY averted (95% uncertainty range $49$239) in Uganda, reflecting the lower treatment costs in Uganda. Cost utility was most sensitive to assay specificity, cost of anti-tuberculosis treatment, life expectancy after TB cure and cohort TB prevalence, but did not rise above $1500 per DALY averted in South Africa under any one-way sensitivity analysis. The probability of acceptability was >99.8% at a per-DALY willingness-to-pay threshold equal to the per capita gross domestic product in South Africa ($7275) and Uganda ($509).
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Affiliation(s)
- D Sun
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland 21205, USA
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Arentz M, Pavlinac P, Kimerling ME, Horne DJ, Falzon D, Schünemann HJ, Royce S, Dheda K, Walson JL. Use of anti-retroviral therapy in tuberculosis patients on second-line anti-TB regimens: a systematic review. PLoS One 2012; 7:e47370. [PMID: 23144818 PMCID: PMC3489892 DOI: 10.1371/journal.pone.0047370] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2012] [Accepted: 09/12/2012] [Indexed: 01/25/2023] Open
Abstract
INTRODUCTION Use of antiretroviral therapy (ART) during treatment of drug susceptible tuberculosis (TB) improves survival. However, data from HIV infected individuals with drug resistant TB are lacking. Second line TB drugs when combined with ART may increase drug interactions and lead to higher rates of toxicity and greater noncompliance. This systematic review sought to determine the benefit of ART in the setting of second line drug therapy for drug resistant TB. METHODS We included individual patient data from studies that evaluated treatment of drug-resistant tuberculosis in HIV-1 infected individuals published between January 1980 and December of 2009. We evaluated the effect of ART on treatment outcomes, time to smear and culture conversion, and adverse events. RESULTS Ten observational studies, including data from 217 subjects, were analyzed. Patients using ART during TB treatment had increased likelihood of cure (hazard ratio (HR) 3.4, 95% CI 1.6-7.4) and decreased likelihood of death (HR 0.4, 95% CI 0.3-0.6) during treatment for drug resistant TB. These associations remained significant in patients with a CD4 less than 200 cells/mm(3) and less than 50 cells/mm(3), and when correcting for drug resistance pattern. LIMITATIONS We identified only observational studies from which individual patient data could be drawn. Limitations in study design, and heterogeneity in a number of the outcomes of interest had the potential to introduce bias. DISCUSSION While there are insufficient data to determine if ART use increases adverse drug interactions when used with second line TB drugs, ART use during treatment of drug resistant TB appears to improve cure rates and decrease risk of death. All individuals with HIV appear to benefit from ART use during treatment for TB.
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Affiliation(s)
- Matthew Arentz
- The University of Washington, Seattle, Washington, United States of America.
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Vitamin D rescues impaired Mycobacterium tuberculosis-mediated tumor necrosis factor release in macrophages of HIV-seropositive individuals through an enhanced Toll-like receptor signaling pathway in vitro. Infect Immun 2012; 81:2-10. [PMID: 23071135 DOI: 10.1128/iai.00666-12] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/03/2023] Open
Abstract
Mycobacterium tuberculosis disease represents an enormous global health problem, with exceptionally high morbidity and mortality in HIV-seropositive (HIV(+)) persons. Alveolar macrophages from HIV(+) persons demonstrate specific and targeted impairment of critical host cell responses, including impaired M. tuberculosis-mediated tumor necrosis factor (TNF) release and macrophage apoptosis. Vitamin D may promote anti-M. tuberculosis responses through upregulation of macrophage NO, NADPH oxidase, cathelicidin, and autophagy mechanisms, but whether vitamin D promotes anti-M. tuberculosis mechanisms in HIV(+) macrophages is not known. In the current study, human macrophages exposed to M. tuberculosis demonstrated robust release of TNF, IκB degradation, and NF-κB nuclear translocation, and these responses were independent of vitamin D pretreatment. In marked contrast, HIV(+) U1 human macrophages exposed to M. tuberculosis demonstrated very low TNF release and no significant IκB degradation or NF-κB nuclear translocation, whereas vitamin D pretreatment restored these critical responses. The vitamin D-mediated restored responses were dependent in part on macrophage CD14 expression. Importantly, similar response patterns were observed with clinically relevant human alveolar macrophages from healthy individuals and asymptomatic HIV(+) persons at high clinical risk of M. tuberculosis infection. Taken together with the observation that local bronchoalveolar lavage fluid (BALF) levels of vitamin D are severely deficient in HIV(+) persons, the data from this study demonstrate that exogenous vitamin D can selectively rescue impaired critical innate immune responses in vitro in alveolar macrophages from HIV(+) persons at risk for M. tuberculosis disease, supporting a potential role for exogenous vitamin D as a therapeutic adjuvant in M. tuberculosis infection in HIV(+) persons.
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Nahid P, Menzies D. Update in tuberculosis and nontuberculous mycobacterial disease 2011. Am J Respir Crit Care Med 2012; 185:1266-70. [PMID: 22707733 DOI: 10.1164/rccm.201203-0494up] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
The number of tuberculosis (TB) cases and global TB incidence rates is decreasing according to the latest World Health Organization Global Tuberculosis Report (1). This is very welcome news. However, the 8.8 million incident cases of TB, 1.1 million deaths from TB among HIV-negative people, the 350,000 deaths from HIV-associated TB, and the millions of children orphaned as a result of parental deaths caused by TB provide a stark reminder of the magnitude of devastation caused by TB each year. Advances in understanding TB epidemiology diagnosis and treatment in 2011, many of which were reported in the Journal, provide hope that the annual decline in TB cases will accelerate.
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Affiliation(s)
- Payam Nahid
- Division of Pulmonary and Critical Care Medicine and Curry International Tuberculosis Center, University of California, San Francisco at San Francisco General Hospital, San Francisco, CA 94110, USA.
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Walker NF, Clark SO, Oni T, Andreu N, Tezera L, Singh S, Saraiva L, Pedersen B, Kelly DL, Tree JA, D'Armiento JM, Meintjes G, Mauri FA, Williams A, Wilkinson RJ, Friedland JS, Elkington PT. Doxycycline and HIV infection suppress tuberculosis-induced matrix metalloproteinases. Am J Respir Crit Care Med 2012; 185:989-97. [PMID: 22345579 DOI: 10.1164/rccm.201110-1769oc] [Citation(s) in RCA: 110] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/29/2023] Open
Abstract
RATIONALE Tuberculosis kills more than 1.5 million people per year, and standard treatment has remained unchanged for more than 30 years. Tuberculosis (TB) drives matrix metalloproteinase (MMP) activity to cause immunopathology. In advanced HIV infection, tissue destruction is reduced, but underlying mechanisms are poorly defined and no current antituberculous therapy reduces host tissue damage. OBJECTIVES To investigate MMP activity in patients with TB with and without HIV coinfection and to determine the potential of doxycycline to inhibit MMPs and decrease pathology. METHODS Concentrations of MMPs and cytokines were analyzed by Luminex array in a prospectively recruited cohort of patients. Modulation of MMP secretion and Mycobacterium tuberculosis growth by doxycycline was studied in primary human cells and TB-infected guinea pigs. MEASUREMENTS AND MAIN RESULTS HIV coinfection decreased MMP concentrations in induced sputum of patients with TB. MMPs correlated with clinical markers of tissue damage, further implicating dysregulated protease activity in TB-driven pathology. In contrast, cytokine concentrations were no different. Doxycycline, a licensed MMP inhibitor, suppressed TB-dependent MMP-1 and -9 secretion from primary human macrophages and epithelial cells by inhibiting promoter activation. In the guinea pig model, doxycycline reduced lung TB colony forming units after 8 weeks in a dose-dependent manner compared with untreated animals, and in vitro doxycycline inhibited mycobacterial proliferation. CONCLUSIONS HIV coinfection in patients with TB reduces concentrations of immunopathogenic MMPs. Doxycycline decreases MMP activity in a cellular model and suppresses mycobacterial growth in vitro and in guinea pigs. Adjunctive doxycycline therapy may reduce morbidity and mortality in TB.
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Affiliation(s)
- Naomi F Walker
- Infectious Diseases and Immunity, Imperial College London, London, UK
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Abstract
Mycobacterium tuberculosis is an old enemy of the human race, with evidence of infection observed as early as 5000 years ago. Although more host-restricted than Mycobacterium bovis, which can infect all warm-blooded vertebrates, M. tuberculosis can infect, and cause morbidity and mortality in, several veterinary species as well. As M. tuberculosis is one of the earliest described bacterial pathogens, the literature describing this organism is vast and overwhelming. This review strives to distill what is currently known about this bacterium and the disease it causes for the veterinary pathologist.
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Affiliation(s)
- K Sakamoto
- Department of Pathology, College of Veterinary Medicine, University of Georgia, 501 D. W. Brooks Dr, Athens, GA 30602-7388, USA.
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Sbrana E, Grise J, Stout C, Aronson J. Co-morbidities associated with tuberculosis in an autopsy case series. Tuberculosis (Edinb) 2011; 91 Suppl 1:S38-42. [DOI: 10.1016/j.tube.2011.10.008] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
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