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Mathematical model tuberculosis

Devyani Deshpande, Shashikant Srivastava, Eric Nuermberger, Jotam G Pasipanodya, Soumya Swaminathan, Tawanda Gumbo
BACKGROUND:  No treatment regimens have been specifically designed for children, in whom tuberculosis is predominantly intracellular. Given their activity as monotherapy and their ability to penetrate many diseased anatomic sites that characterize disseminated tuberculosis, linezolid and moxifloxacin could be combined to form a regimen for this need. METHODS:  We examined microbial kill of intracellular Mycobacterium tuberculosis (Mtb) by the combination of linezolid and moxifloxacin multiple exposures in a 7-by-7 mathematical matrix...
November 1, 2016: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
Rein M G J Houben, Nicolas A Menzies, Tom Sumner, Grace H Huynh, Nimalan Arinaminpathy, Jeremy D Goldhaber-Fiebert, Hsien-Ho Lin, Chieh-Yin Wu, Sandip Mandal, Surabhi Pandey, Sze-Chuan Suen, Eran Bendavid, Andrew S Azman, David W Dowdy, Nicolas Bacaër, Allison S Rhines, Marcus W Feldman, Andreas Handel, Christopher C Whalen, Stewart T Chang, Bradley G Wagner, Philip A Eckhoff, James M Trauer, Justin T Denholm, Emma S McBryde, Ted Cohen, Joshua A Salomon, Carel Pretorius, Marek Lalli, Jeffrey W Eaton, Delia Boccia, Mehran Hosseini, Gabriela B Gomez, Suvanand Sahu, Colleen Daniels, Lucica Ditiu, Daniel P Chin, Lixia Wang, Vineet K Chadha, Kiran Rade, Puneet Dewan, Piotr Hippner, Salome Charalambous, Alison D Grant, Gavin Churchyard, Yogan Pillay, L David Mametja, Michael E Kimerling, Anna Vassall, Richard G White
BACKGROUND: The post-2015 End TB Strategy proposes targets of 50% reduction in tuberculosis incidence and 75% reduction in mortality from tuberculosis by 2025. We aimed to assess whether these targets are feasible in three high-burden countries with contrasting epidemiology and previous programmatic achievements. METHODS: 11 independently developed mathematical models of tuberculosis transmission projected the epidemiological impact of currently available tuberculosis interventions for prevention, diagnosis, and treatment in China, India, and South Africa...
November 2016: Lancet Global Health
Rebecca C Harris, Peter J Dodd, Richard G White
BACKGROUND: The Bacillus Calmette-Guérin (BCG) vaccine is provided to over 100 million neonates annually to protect against childhood tuberculosis (TB). Recent BCG manufacturing interruptions highlight global supply risks. We estimated the potential impact of BCG shortfalls on global paediatric (<15 years) TB mortality. METHODS: A static mathematical model was employed to estimate the number of paediatric TB deaths avoided by usual levels of BCG coverage, and potential additional TB deaths in the first 15 years of life due to 1-year BCG supply shortfalls of 6...
2016: BMC Medicine
Andreas Sandgren, Jannigje M Vonk Noordegraaf-Schouten, Anouk M Oordt-Speets, Gerarda B van Kessel, Sake J de Vlas, Marieke J van der Werf
Individuals with latent tuberculosis infection (LTBI) are the reservoir of Mycobacterium tuberculosis in a population and as long as this reservoir exists, elimination of tuberculosis (TB) will not be feasible. In 2013, the European Centre for Disease Prevention and Control (ECDC) started an assessment of benefits and risks of introducing programmatic LTBI control, with the aim of providing guidance on how to incorporate LTBI control into national TB strategies in European Union/European Economic Area (EU/EEA) Member States and candidate countries...
August 25, 2016: Euro Surveillance: Bulletin Européen sur les Maladies Transmissibles, European Communicable Disease Bulletin
Amber Kunkel, Forrest W Crawford, James Shepherd, Ted Cohen
OBJECTIVE: Extending the duration of isoniazid preventive therapy (IPT) among people living with HIV (PLHIV) may improve its effectiveness at both the individual and population level, but could also increase selective pressure in favor of isoniazid resistant tuberculosis (TB) strains. The objective of this study was to determine the relative importance of these two effects. METHODS: Transmission dynamic model DESIGN:: We created a mathematical model of TB transmission incorporating HIV incidence and treatment, mixed strain latent TB infections, and four different phenotypes of TB drug resistance (pan-susceptible, isoniazid mono-resistant, rifampicin mono-resistant, and multi-drug resistant)...
August 17, 2016: AIDS
Rebecca H Chisholm, James M Trauer, Darren Curnoe, Mark M Tanaka
Tuberculosis (TB) is caused by the Mycobacterium tuberculosis complex (MTBC), a wildly successful group of organisms and the leading cause of death resulting from a single bacterial pathogen worldwide. It is generally accepted that MTBC established itself in human populations in Africa and that animal-infecting strains diverged from human strains. However, the precise causal factors of TB emergence remain unknown. Here, we propose that the advent of controlled fire use in early humans created the ideal conditions for the emergence of TB as a transmissible disease...
August 9, 2016: Proceedings of the National Academy of Sciences of the United States of America
Rebecca C Harris, Tom Sumner, Gwenan M Knight, Richard G White
Mathematical models are useful for assessing the potential epidemiological impact of future tuberculosis (TB) vaccines. We conducted a systematic review of mathematical models estimating the epidemiological impact of future human TB vaccines. PubMed, Embase and WHO Global Health Library were searched, 3-stage manual sifted, and citation- and reference-tracked, identifying 23 papers. An adapted quality assessment tool was developed, with a resulting median study quality score of 20/28. The literature remains divided as to whether vaccines effective pre- or post-infection would provide greatest epidemiological impact...
July 22, 2016: Human Vaccines & Immunotherapeutics
Frederick L Altice, Lyuba Azbel, Jack Stone, Ellen Brooks-Pollock, Pavlo Smyrnov, Sergii Dvoriak, Faye S Taxman, Nabila El-Bassel, Natasha K Martin, Robert Booth, Heino Stöver, Kate Dolan, Peter Vickerman
Despite global reductions in HIV incidence and mortality, the 15 UNAIDS-designated countries of Eastern Europe and Central Asia (EECA) that gained independence from the Soviet Union in 1991 constitute the only region where both continue to rise. HIV transmission in EECA is fuelled primarily by injection of opioids, with harsh criminalisation of drug use that has resulted in extraordinarily high levels of incarceration. Consequently, people who inject drugs, including those with HIV, hepatitis C virus, and tuberculosis, are concentrated within prisons...
September 17, 2016: Lancet
Margaret M McDaniel, Nitin Krishna, Winode G Handagama, Shigetoshi Eda, Vitaly V Ganusov
When an individual is exposed to Mycobacterium tuberculosis (Mtb) three outcomes are possible: bacterial clearance, active disease, or latent infection. It is generally believed that most individuals exposed to Mtb become latently infected and carry the mycobacteria for life. How Mtb is maintained during this latent infection remains largely unknown. During an Mtb infection in mice, there is a phase of rapid increase in bacterial numbers in the murine lungs within the first 3 weeks, and then bacterial numbers either stabilize or increase slowly over the period of many months...
2016: Frontiers in Microbiology
Peter J Dodd, Charalambos Sismanidis, James A Seddon
BACKGROUND: After infection with Mycobacterium tuberculosis, children are at an increased risk of progression to tuberculosis disease; a condition that can be challenging to diagnose. New estimation approaches for children have highlighted the gap between incidence and notifications of M tuberculosis, and suggest there are more cases of isoniazid-resistant and multidrug-resistant (MDR) disease than are identified. No work has yet quantified the burden of drug-resistant infection, or accounted for other types of drug resistance or sampling uncertainty...
October 2016: Lancet Infectious Diseases
Serge Ade, Wilfried Békou, Mênonli Adjobimey, Omer Adjibode, Gabriel Ade, Anthony D Harries, Séverin Anagonou
Objective. To determine any changes in tuberculosis epidemiology in the last 15 years in Benin, seasonal variations, and forecasted numbers of tuberculosis cases in the next five years. Materials and Methods. Retrospective cohort and time series study of all tuberculosis cases notified between 2000 and 2014. The "R" software version 3.2.1 (Institute for Statistics and Mathematics Vienna Austria) and the Box-Jenkins 1976 modeling approach were used for time series analysis. Results. Of 246943 presumptive cases, 54303 (22%) were diagnosed with tuberculosis...
2016: Tuberculosis Research and Treatment
G Sánchez-González
OBJECTIVES: The objective of this study was to estimate the cost-effectiveness of treating patients infected with HIV and simultaneously coinfected with tuberculosis (TB) and hepatitis C virus (HCV). METHODS: A mathematical model for HIV coinfection with TB and HCV is introduced. The model was designed to incorporate parameters of control for the coverage of care, which makes it useful for performing cost-effectiveness analysis of public policies. A cost-effectiveness analysis of early medical care of patients with TB and HCV coinfection, with coverage of 0 (basal), 25, 50, 75 and 100%, was performed for the whole cohort of patients and a special analysis was performed in a selected population with triple infection...
October 2016: HIV Medicine
Robert S Wallis
The natural history of human infection with Mycobacterium tuberculosis (Mtb) is highly variable, as is the response to treatment of active tuberculosis. There is presently no direct means to identify individuals in whom Mtb infection has been eradicated, whether by a bactericidal immune response or sterilizing antimicrobial chemotherapy. Mathematical models can assist in such circumstances by measuring or predicting events that cannot be directly observed. The 3 models discussed in this review illustrate instances in which mathematical models were used to identify individuals with innate resistance to Mtb infection, determine the etiologic mechanism of tuberculosis in patients treated with tumor necrosis factor blockers, and predict the risk of relapse in persons undergoing tuberculosis treatment...
2016: Frontiers in Microbiology
Peter J White, Ibrahim Abubakar
Tuberculosis control and elimination remains a challenge for public health even in low-burden countries. New technology and novel approaches to case-finding, diagnosis, and treatment are causes for optimism but they need to be used cost-effectively. This in turn requires improved understanding of the epidemiology of TB and analysis of the effectiveness and cost-effectiveness of different interventions. We describe the contribution that mathematical modeling can make to understanding epidemiology and control of TB in different groups, guiding improved approaches to public health interventions...
2016: Frontiers in Microbiology
James M Trauer, Justin T Denholm, Saba Waseem, Romain Ragonnet, Emma S McBryde
Tuberculosis (TB) and multidrug-resistant TB (MDR-TB) are major health problems in Western Province, Papua New Guinea. While comprehensive expansion of TB control programs is desirable, logistical challenges are considerable, and there is substantial uncertainty regarding the true disease burden. We parameterized our previously described mathematical model of Mycobacterium tuberculosis dynamics in Western Province, following an epidemiologic assessment. Five hypothetical scenarios representing alternative programmatic approaches during the period from 2013 to 2023 were developed with local staff...
June 15, 2016: American Journal of Epidemiology
Rebecca H Chisholm, Mark M Tanaka
Mycobacterium tuberculosis has an unusual natural history in that the vast majority of its human hosts enter a latent state that is both non-infectious and devoid of any symptoms of disease. From the pathogen perspective, it seems counterproductive to relinquish reproductive opportunities to achieve a détente with the host immune response. However, a small fraction of latent infections reactivate to the disease state. Thus, latency has been argued to provide a safe harbour for future infections which optimizes the persistence of M...
May 25, 2016: Proceedings. Biological Sciences
Xia Zhou, Peiling Yap, Marcel Tanner, Robert Bergquist, Jürg Utzinger, Xiao-Nong Zhou
The peer-reviewed journal Infectious Diseases of Poverty provides a new platform to engage with, and disseminate in an open-access format, science outside traditional disciplinary boundaries. The current piece reviews a thematic series on surveillance-response systems for elimination of tropical diseases. Overall, 22 contributions covering a broad array of diseases are featured - i.e. clonorchiasis, dengue, hepatitis, human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS), H7N9 avian influenza, lymphatic filariasis, malaria, Middle East respiratory syndrome (MERS), rabies, schistosomiasis and tuberculosis (TB)...
2016: Infectious Diseases of Poverty
Patrick B Phepa, Faraimunashe Chirove, Keshlan S Govinder
A mathematical model that describes the transmission dynamics of bovine tuberculosis (BTB) in both buffalo and cattle populations is proposed. The model incorporates cross-infection and contaminated environment transmission routes. A full analysis of the model is undertaken. The reproduction number of the entire model is comprised of cross-infection and contaminated parameters. This underscores the importance of including both cross-infection and contaminated environment transmission routes. Crucially our simulations suggest that the disease has a more devastating effect on cattle populations than on buffalo populations when all transmission routes are involved...
July 2016: Mathematical Biosciences
Laure Lalande, Laurent Bourguignon, Pascal Maire, Sylvain Goutelle
Tuberculosis (TB) treatment needs to be optimized as it is currently long and associated with increasing drug resistance. The antimycobacterial effect of isoniazid (INH) is characterized by a biphasic kill curve, whose causes are still debated. In this work, we developed a complete mathematical model describing the time-course of TB infection and its treatment by INH in human lung. This model was based on a pharmacokinetic model, a pharmacodynamic model and a pathophysiological model. It was used to simulate the antibacterial effect of INH during the first days of therapy...
June 21, 2016: Journal of Theoretical Biology
Sourya Shrestha, Susmita Chatterjee, Krishna D Rao, David W Dowdy
Some of the most promising vaccines in the pipeline for tuberculosis (TB) target adolescents and adults. Unlike for childhood vaccines, high-coverage population-wide vaccination is significantly more challenging for adult vaccines. Here, we aimed to estimate the impact of vaccine delivery strategies that were targeted to high-incidence geographical 'hotspots' compared with randomly allocated vaccination. We developed a spatially explicit mathematical model of TB transmission that distinguished these hotspots from the general population...
March 2016: Journal of the Royal Society, Interface
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