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Dissertations / Theses on the topic 'TB diagnosis'

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Published: 4 June 2021
Last updated: 10 February 2022

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1

Dinic, Lana. "Molecular Diagnosis of TB and MDR-TB in HIV-Coinfection in Nigeria." Thesis, Harvard University, 2012. http://dissertations.umi.com/gsas.harvard:10387.

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Tuberculosis (TB) is the most common opportunistic infection in HIV-infected patients and the emergence of drug-resistant tuberculosis (DR-TB) is a growing problem in resource-limited settings (RLS). TB diagnosis in most RLS still depends on smear microscopy for acid-fast bacilli (AFB) while adequate infrastructure for testing drug sensitivity is unavailable. However, molecular diagnostics that detect Mycobacterium tuberculosis (Mtb) DNA and its genetic markers of drug resistance were recently developed. In this thesis I describe the use of a molecular diagnostic, Genotype MTBDRplus, for characterizing DR-TB and patterns of tuberculosis-like infection in two cities in south-west and north-central Nigeria. I found high rates of DR-TB in Nigerian HIV-infected individuals (9.3% for RIF or INH) with significantly different amounts by location (18.18% in south-west vs. 3.91% in north-central Nigeria, p=0.01). RIF resistance, indicative of MDR-TB, was found in 5.52% treatment-naïve patients, far exceeding the WHO predictions (0-4.3%). Furthermore, RIF resistance was genetically distinct, suggesting location-specific transmission of drug resistance (p=0.04). Genotype MTBDRplus correctly identified the drug-resistant samples compared to sequencing in 96.8% of cases. Mtb was confirmed in 56% of patients and was less likely to be found in patients on ART, while controlling for other relevant demographic characteristics (OR 0.29, P=0.02). Only abnormal respiratory findings on auscultation and the direct sputum smear grade greater than 3/100 were significant predictors of Mtb infection (OR 3.28, P=0.03; OR 6.40, p<0.01 respectively). Concentrated sputum smear was not significantly correlated with Mtb infection, except at the highest grades (>2+). Furthermore, in 49% of samples that were not confirmed for Mtb other actinomycetes were found: atypical Mycobacteria (ATM), Rhodococcus spp., Nocardia spp., Corynebacterium spp. I conclude that concentrated sputum AFB smears may misidentify bacteria as Mtb in a subset of HIV-infected patients. These individuals may have a different, even uncharacterized, actinomycete infection in the respiratory tract. Furthermore, total DR-TB in HIV-infection is high and transmission of DR-TB in HIV-infected patients in Nigeria is higher than estimated by the WHO. Molecular diagnostics are a rapid method for identifying Mtb and monitoring DR-TB, and can guide appropriate treatment decisions for respiratory infections in RLS with a high HIV burden.
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2

Brent, Andrew. "The Kilifi Improving Diagnosis and Surveillance of Childhood TB Study : the KIDS TB Study." Thesis, Imperial College London, 2013. http://hdl.handle.net/10044/1/14399.

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Improving diagnosis and surveillance of childhood TB are key research priorities. We established intensified case finding and state of the art TB diagnostics to investigate the performance of clinical and laboratory tools for childhood TB diagnosis at 2 hospitals in Kenya. We estimated the community incidence of childhood TB using a continuous demographic surveillance survey and detailed surveillance sensitivity analysis. 2041 children were investigated for suspected TB. 70 (3.4%) had bacteriologically confirmed TB, 63 (3.1%) had clinically highly probable TB, and a further 144 (7.1%) were treated for TB based on their clinical presenting features. 107/133 (80%) confirmed/highly probable TB (CHPTB) cases had pulmonary TB. CHPTB was associated with HIV infection (OR 2.1, 95% CI 1.3-3.2), malnutrition (1.5, 1.0-2.1) and close TB contact (5.7, 3.8-8.5). The population attributable fraction of a known close TB contact was 38.8-52.5%. The estimated community incidence of CHPTB locally and nationally was 46 and 83 per 100,000 per year, respectively. The performance of published clinical diagnostic tools varied widely, but the accuracy of all was limited. We derived and independently validated a simple KIDS TB Score that ruled out TB in 2/3 suspects with 98.8% negative predictive value, stratifying other children into groups of increasing risk. Bacteriological yield was highest for the Mycobacterial Growth Inhibitor Tube (MGIT) method (sensitivity 34%, 29-39%, among CHPTB patient samples), and lower for the Microscopic Observation Drug Susceptibility (MODS) assay (30%, 24-35%). The study provides the first comprehensive description from the region of the clinical spectrum of childhood TB, and the only prospective incidence estimates. It suggests up to half of all cases are potentially preventable by implementing current recommendations for isoniazid chemoprophylaxis. The diagnostic performance of clinical and laboratory methods should inform development of future clinical guidelines and laboratory capacity.
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3

Koeslag, Anthony. "Computer aided diagnosis of miliary TB in chest X-rays." Master's thesis, University of Cape Town, 2001. http://hdl.handle.net/11427/5191.

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With the improvement in computer technology, Computer Aided Diagnosis (CAD) is becoming an increasingly more powerful tool for radiologists. The focus of this project was on CAD of pulmonary miliary tuberculosis. Several methods for enhancing lung textures were discussed as an aid to the radiologist in diagnosing miliary TB. Some statistical approaches and template matching methods were used to measure characteristics of both healthy and unhealthy (miliary TB) lung textures. These measurements were evaluated to see if a computer can be programmed to differentiate between lung texture from a healthy lung and lung texture from a lung with miliary TB.
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4

Tomlinson, Catherine Reid. "Linkage to treatment following RR-TB diagnosis in the Western Cape." Master's thesis, University of Cape Town, 2015. http://hdl.handle.net/11427/16776.

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Patients diagnosed with rifampicin resistant (RR) tuberculosis (TB) in South Africa frequently fail to link to appropriate drug resistant (DR) TB treatment. The aim of this study was to explore barriers and enablers to expedited linkage to treatment following RR-TB diagnosis in the Western Cape Province, within the context of ongoing decentralisation of DRTB services and the scale-up of Xpert MTB/RIF diagnostics. Methods: An embedded case study approach, using qualitative research methods, was employed to explore barriers and enablers to expedited treatment linkage following RR-TB diagnosis. The case of investigation in this study was 'treatment linkage following RR-TB diagnosis in the Western Cape Province during the ongoing decentralisation of DR-TB services and scale-up of Xpert diagnostics'. DR-TB is used in this study as an encompassing term to refer to RR, multidrug resistant and extensively drug resistant TB. The embedded units of analysis in this study were patients' linkage outputs, defined as: (1) expedited treatment initiation, (2) delayed treatment initiation and (3) non-initiation of treatment following sputum collection on which RR-TB was diagnosed. Seventeen patient, 8 family member, 49 healthcare worker and 4 key informant open-ended, in-depth interviews were conducted and 59 patient folders were reviewed. Additionally, an extensive literature review was conducted. The tools used for data collection in this study were developed from the literature review and Coker et al.'s (201) conceptual framework for evaluation of a communicable disease intervention. A framework approach using Coker et al.'s conceptual framework was applied for analysis. Results: This study identified multiple factors that enabled and constrained expedited treatment linkage following RR-TB diagnosis. Enabling factors included: 1) the availability of clinic level DR-TB counsellors and tracers; 2) living in walking distance of decentralised services and 3) having a strong social support network. Constraining factors included: 1) low usage of Xpert diagnostics, 2) delays in acting on results and missed (or unseen) results, 3) rotation of nurses or the lack of dedicated TB nurses in clinics, 4) limited clinic-level administrative support, 5) information systems challenges and 6) waiting lists for beds and limited access to transport services in rural areas . In linking to treatment, patients commonly face challenges due to competing subsistence needs and household or employment responsibilities. Additionally, substance addiction, having a history of treatment interruption, hopelessness regarding treatment, as well as not having a stable place to stay or social support may increase patients' risks of linkage failure. Conclusion: Within the Western Cape Province, there is significant opportunity to improve linkage to treatment through strengthening the health systems mechanisms to link patients to treatment following RR-TB diagnosis. Expanding access to psychosocial services (substance abuse rehabilitation and psychosocial evaluations) following RR-TB diagnosis may assist in linking high-risk patients to treatment. Additionally, the provision of food support (in addition to social grants) should be evaluated as a tactic to improve treatment linkage and adherence.
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Orikiriza, Patrick. "Improving diagnosis of childhood tuberculosis in a high TB-HIV prevalent setting." Thesis, Montpellier, 2019. http://www.theses.fr/2019MONTT026.

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L’Organisation Mondiale de la Santé estime qu’en 2017 près d’un million d’enfants de moins de 15 ans ont développé la tuberculose mais seulement la moitié des cas ont été notifiés. Les difficultés pour recueillir des échantillons de crachat chez les enfants et la nature paucibacillifère de la tuberculose pédiatrique représentent de véritables challenges diagnostiques. Cela aboutit à la prescription fréquente de traitement empirique avec un risque de sur- ou sous-diagnostic. De plus, peu de laboratoires dans les pays à ressources limitées ont les capacités du diagnostic de la tuberculose. Les échantillons doivent être transportés vers des laboratoires de référence pouvant affecter les performances des tests, notamment en l’absence de chaine de froid.Trois études ont été menées à Mbarara (Ouganda) pour évaluer des échantillons non-respiratoires et des méthodes de conservation des échantillons pour améliorer le diagnostic de la tuberculose de l’enfant. Dans la première étude, nous avons évalué les performances de l’XpertMTB/RIF sur les expectorations et les selles d’enfants avec présomption de tuberculose et nous avons documenté le devenir des enfants selon la décision thérapeutique. Dans la deuxième étude, nous avons évalué les performances de l’XpertMTB/RIF dans les selles et du test lipoarabinomanann (LAM) dans les urines chez des enfants admis dans un état critique. Dans la troisième étude, nous avons déterminé le taux de détection avec XpertMTB/RIF et la culture MGIT d’échantillons de crachats frottis-positifs conservés à température ambiante sans traitement, ou traités avec Omnigène ou éthanol à différents périodes de temps.Sur 392 enfants (âge médian 3,9 ans, 45,5% de filles et 31% VIH positifs) inclus dans la 1e étude, 4,3% ont été confirmés microbiologiquement. L’XpertMTB/RIF dans le crachat avait une sensibilité de 90,9% et une spécificité de 99,1% contre un test de référence microbiologique. La sensibilité et la spécificité de l’Xpert dans les selles étaient de 55,6% et 98,2%. La mortalité était de 6,9% à trois mois, et était plus importante chez les enfants traités (10,7%) que chez les enfants non-traités (4,5%). Aucun des enfants traités pour une tuberculose microbiologiquement confirmée n’est décédé contre 12,3% de ceux traités de façon empirique.Parmi les 234 enfants (âge médian 16,5 mois, 48,3% de filles, 31,6% VIH positifs et 58,5% sévèrement malnutris) inclus dans la 2e étude, 5,1% avaient une tuberculose microbiologiquement confirmée. XpertMTB/RIF dans les selles avait une sensibilité de 50% et une spécificité de 99,1%. La sensibilité du test urinaire LAM était de 50% et la spécificité de 74,1%. Les faux positifs LAM étaient plus fréquents parmi les résultats positifs LAM de bas grade et dans les urines avec une contamination bactérienne.Dans la 3e étude, après 15jours, il n’y avait pas de différence de détection par XpertMTB/RIF entre les échantillons traités avec Omnigène ou éthanol et les échantillons non traités, ne montrant pas de bénéfice de l’ajout d’un conservateur. Nous avons décrit une baisse substantielle de viabilité de Mycobacterium tuberculosis dans les échantillons traités par Omnigène, ce qui n’est pas en faveur de l’utilisation de l’Omnigène pour le transport des échantillons avant culture MGIT.En conclusion, XpertMTB/RIF dans les selles a montré des résultats prometteurs chez les enfants ne pouvant pas cracher et pourrait être une alternative intéressante à des méthodes plus complexes comme l’induction du crachat et l’aspiration gastrique pour les centres de santé primaire des pays à ressources limitées. La faible spécificité du LAM dans les urines nécessite des investigations complémentaires avant son utilisation pour le diagnostic de la tuberculose de l’enfant. En dépit des résultats encourageants de l’XpertMTB/RIF sur les échantillons conservés avec Omnigène ou l’éthanol, des investigations complémentaires dans des conditions programmatiques sont nécessaires
The world health organization estimates that in 2017, close to 1 million children below 15 years developed tuberculosis but only half of them were notified. Difficulty to obtain sputum in children and the paucibacillary nature of intrathoracic childhood tuberculosis challenge the diagnosis of tuberculosis in children. This leads to the common use of empirical treatment with a high risk of over or under diagnosis. Besides that, few facilities in low resource settings have adequate laboratory capacity to diagnose tuberculosis. Samples must be transported to a reference laboratory, which can effect performance of the tests, especially in the absence of cold chain.Three studies were conducted in Mbarara (Uganda) to evaluate non-respiratory samples and specimen preservation methods to improve diagnosis of pediatric tuberculosis. In the first study, we assessed the performance of XpertMTB/RIF on sputum and stool in children with presumptive tuberculosis and documented outcomes of children according to the tuberculosis treatment decision. In the second study, we assessed the performance of stool XpertMTB/RIF and urine lipoarabinomanann (LAM) among children admitted with severe illness. In the 3rd study, we determined XpertMTB/RIF and MGIT culture recovery rates of smear positive sputum specimen kept untreated at room temperature and treated with either Omnigene or ethanol over different time periods.Of 392 children (median age 3.9 years, 45.4% female and 31% HIV infected) enrolled in the 1st study, 4.3% (17/392) were microbiologically confirmed tuberculosis. Using a microbiological reference standard, sputum XpertMTB/RIF had a 90.9% sensitivity and specificity of 99.1%. The sensitivity and specificity of stool XpertMTB/RIF was 55.6% and 98.2%. The study reported mortality of 6.9% within three months with a higher proportion (10.7%) among children treated for tuberculosis compared to the non-treated children (4.5%). None of treated children with bacteriologically confirmed tuberculosis died compared to 12.3% of those treated empirically.Of 234 patients (median age 16.5 months, 48.3% female, 31.6% HIV infected, 58.5% severely malnourished) enrolled in the 2nd study, 5.1% were microbiologically confirmed tuberculosis. Stool XpertMTB/RIF had a sensitivity of 50% and specificity of 99.1%. For the urine LAM test, it was 50% and 74.1%, respectively. False positive LAM results were more common among low grade positive LAM results and occurred more frequently when urine samples had bacterial contamination.The 3rd study documented that by 15th day, there was no difference of XpertMTB/RIF recovery rate between samples treated with Omnigene or ethanol and untreated samples, meaning that in the study conditions there was no benefit of adding any preservative for samples stored at room temperature up to 15 days. We observed a substantial loss of viability of Mycobacterium tuberculosis on samples treated with Omnigene, which does not support the use of Omnigene for sample transportation before MGIT testing.In conclusion, XpertMTB/RIF on stool gave promising results for the use in children unable to provide sputum and could be an interesting alternative to more complex methods such as sputum induction and gastric aspirate for primary health care centers of limited resource countries. The low specificity of the urine LAM requires further investigation before its use for diagnosis of tuberculosis in children. Despite the encouraging XpertMTB/RIF results from specimen preserved either with Omnigene or ethanol further evaluation under routine field conditions is necessary
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6

Matinyenya, Brian. "Novel and newer nucleic acid amplification tests for the diagnosis of TB." Master's thesis, University of Cape Town, 2016. http://hdl.handle.net/11427/20680.

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Background: Current tools for TB diagnosis have suboptimal accuracy, perform poorly in diagnosing extra-pulmonary TB, and are not point of care; hence results have a slow turn-around time. Objective: This project evaluated the diagnostic accuracy of the promising novel loop mediated isothermal amplification (LAMP) assay on sputum, and that of the semi-automated Xpert MTB/RIF (Xpert) test on non-sputum specimens (bronchoalveolar lavage fluid [BALF], tracheal aspirates, and cerebrospinal fluid [CSF]) from South African patients with suspected TB (the accuracy of Xpert using these fluids was unknown at the time this work was performed). Methodology: Biological samples (sputum, tracheal aspirates, BALF, or CSF) were collected from patients with suspected TB. Liquid culture served as the reference standard for the diagnosis of definite TB. Accuracy was evaluated according to HIV and smear microscopy status, where appropriate. The relationship between test performance and bacterial load (culture time-to-positivity [TTP]) was also compared. For the evaluation of LAMP, 2 spot sputa of approximately 4 ml were collected from 301 patients (60 μl of sputum was used for the assay). For the evaluation of Xpert on BALF, 152 patients who were sputum scarce or smear-negative were recruited (1 ml of the BALF aliquot or a re-suspended pellet from 10 ml BALF was used). For the evaluation of Xpert on tracheal aspirates, 120 tracheal aspirates from patients enrolled in the intensive care unit (ICU) were tested. For the evaluation of Xpert on CSF, 235 patients with suspected TBM had a lumbar puncture with 1 ml of CSF or where available a re-suspended pellet from 3 ml of CSF evaluated using Xpert.
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Peter, Jonathan G. "Approaches to the diagnosis of smear-negative and sputum-scarce TB in South Africa." Doctoral thesis, University of Cape Town, 2013. http://hdl.handle.net/11427/3453.

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In South Africa, an HIV-endemic setting, the burden of smear-negative (SN) and sputum-scarce (SS) TB is a major public health catastrophe. Diagnostic delay or failure is a key bottleneck. We hypothesised that i) assisted sputum smpling using sputum induction (SI), and ii) the use of the newer diagnostic tools (Xpert MTB/RIF and urine LAM strip), could improve diagnosis of SN or SSTB and impact clinical care. We investigated the accuracy and impact of these approaches at different levels in the health-system.
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Yilma, Lemma. "Pathways to diagnosis and treatment : TB patients' experiences in London : a narrative enquiry and analysis." Thesis, London School of Hygiene and Tropical Medicine (University of London), 2011. http://researchonline.lshtm.ac.uk/1379947/.

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The purpose of this study was to understand TB patients' experiential accounts of access to TB diagnosis and treatment and more specifically about their experiences of medical help from health care professionals. METHOD: This narrative enquiry was undertaken in three boroughs of London, including two boroughs with the highest TB notification rates in the UK. The study involved pilot interviews with ten patients to develop the research question. In-depth narrative interviews with 32 additional patients were then undertaken. All participants were over eighteen years of age. The analysis of narratives involved descriptive; holistic-form and categorical content (themes) approaches to identify story 'plot' and 'subplots' and themes covering the whole of the patients' journeys to treatment. RESULTS: Seven narrative plots and thirty subplots were grouped into six categories of medical help and specific themes embedded in them were grouped in three stages of patients' pathways 'before' 'during' and 'after' diagnosis. These themes are listed below sequentially to illustrate these patients' pathways. 1. Symptoms were misinterpreted and misdiagnosed. 2. Kept on ineffective antibiotics/painkillers for many visits. 3. Referred quickly for suspected TB or other serious illnesses. 4. Referred only when critically ill. 5. Referred when antibiotics and pain killers not helping. 6. Referred only after pushing for referral. 7. Sought help from A&E. 8. Diagnosed immediately after TB testing. 9. Referred to wrong specialist and waited too long. 10. Had to fight for TB test. 11. Had lots of tests but no results. 12. Doubts about diagnosis. 13. Felt ignored and had no information. 14. Felt listened and cared for. 15. Quickly began my treatment. 16. Felt better after treatment, no side-effects. 17. Felt better after treatment with side-effects. 18. Felt needed longer treatment. CONCLUSIONS: The accounts of two thirds of the study participants suggest that their doctors' misunderstanding of their illness and miscommunication with them contributed to delayed diagnosis and treatment ranging from one month to twelve months. TB service providers and commissioners need to raise clinical staff awareness about TB and review the factors hindering doctor-patient communication about TB care. The findings in this research indicate that health service related delay is likely to contribute to increased TB transmission rates in the two research settings in London.
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9

Truyts, Alma. "Towards paper-based micro bio-sensing of biomarker anti-mycolic acid antibodies for TB diagnosis." Diss., University of Pretoria, 2019. http://hdl.handle.net/2263/72118.

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Accessible point of care diagnosis of Tuberculosis (TB) is an essential development to better manage the global epidemic that infects 10 million people annually. Current diagnostics are centralised, causing patient loss to follow up or delays in treatment. Although serological diagnosis using finger-prick blood has been historically insensitive in the diagnosis of TB, the detection of anti-mycolic acid (MA) antibodies in patient sera has been shown to allow accurate diagnosis in HIV-positive, previously infected and TB exposed patients. MA is a unique lipid antigen of mycobacteria with anti-MA antibodies being formed early upon infection in a T-cell independent pathway. This work aimed to contribute towards the development of a lateral flow immunoassay termed MALIA (Mycolate Antibodies Lateral flow Immuno Assay). This diagnostic has the unique lipid antigen MA as the immobilised capture agent and custom developed monoclonal anti-MA chicken antibodies (gallibodies) as the labelled bio-recognition element. Casein hydrolysate was newly applied as a blocker in enzyme-immuno assay (EIA) to characterise the functionality of the gallibodies in order to circumvent import restrictions on bovine milk products. MA dissolved in hexane and immobilised on nitrocellulose was not detected by the passively conjugated gold labelled gallibody conjugate in the lateral flow test (LFT) format, despite the confirmation with lipid staining and EIA that MA remained immobilised and antigenic on nitrocellulose. Various substrates, blockers and running buffers were explored for the LFT to attempt to detect MA. The method of passive conjugation of the gallibodies to gold nanoparticles was chosen as this is a commonly successful and simple strategy for conjugate preparation in LFTs. Initial characterisation of gold labelled gallibody conjugate suggested that the orientation of the gallibody on the nanoparticle may be favourable for binding by anti-chicken antibody (the control) but not MA. The biological activity (MA binding) of the gold labelled conjugate was probed on alternative methods. The results showed that in EIA, gold labelling caused the loss of MA binding but not anti-chicken immunoglobulin binding. This is possibly due to the extra force in the wash steps caused by the presence of the gold nanoparticle. Interaction of gold labelled gallibody conjugate with antigenic MA nanoparticles in transmission electron microscopy showed loss of biological activity, while dynamic light scattering intensity measurement of the same interaction showed a weak interaction similar to that seen between gold labelled bovine serum albumin conjugate with fatty acid coated nanoparticles. To address the challenges uncovered by this research, gallibodies can be re-engineered to increase functional affinity (by increasing the valency) to be able to compensate for activity losses due to labelling. In addition, labelling of MA, rather than gallibodies may result in a successful, inverted MALIA to meet the ultimate aim to drastically change the face of the TB epidemic at the critical fault line – point of care diagnosis. The promising avenues uncovered by this key explorative research must be pursued to actualise this critically important and non-standard LFT technology.
Dissertation (MSc)--University of Pretoria, 2019.
Biochemistry
MSc
Unrestricted
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Li, Ying, John Ehiri, Shenglan Tang, Daikun Li, Yongqiao Bian, Hui Lin, Caitlin Marshall, and Jia Cao. "Factors associated with patient, and diagnostic delays in Chinese TB patients: a systematic review and meta-analysis." BioMed Central, 2013. http://hdl.handle.net/10150/610046.

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BACKGROUND:Delay in seeking care is a major impediment to effective management of tuberculosis (TB) in China. To elucidate factors that underpin patient and diagnostic delays in TB management, we conducted a systematic review and meta-analysis of factors that are associated with delays in TB care-seeking and diagnosis in the country.METHODS:This review was prepared following standard procedures of the Cochrane Collaboration and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement and checklist. Relevant studies published up to November 2012 were identified from three major international and Chinese literature databases: Medline/PubMed, EMBASE and CNKI (China National Knowledge Infrastructure).RESULTS:We included 29 studies involving 38,947 patients from 17 provinces in China. Qualitative analysis showed that key individual level determinants of delays included socio-demographic and economic factors, mostly poverty, rural residence, lack of health insurance, lower educational attainment, stigma and poor knowledge of TB. Health facility determinants included limited availability of resources to perform prompt diagnosis, lack of qualified health workers and geographical barriers.Quantitative meta-analysis indicated that living in rural areas was a risk factor for patient delays (pooled odds ratio (OR) (95% confidence interval (CI)): 1.79 (1.62, 1.98)) and diagnostic delays (pooled OR (95% CI): 1.40 (1.23, 1.59)). Female patients had higher risk of patient delay (pooled OR (95% CI): 1.94 (1.13, 3.33)). Low educational attainment (primary school and below) was also a risk factor for patient delay (pooled OR (95% CI): 2.14 (1.03, 4.47)). The practice of seeking care first from Traditional Chinese Medicine (TMC) providers was also identified as a risk factor for diagnostic delay (pooled OR (95% CI): 5.75 (3.03, 10.94)).CONCLUSION:Patient and diagnostic delays in TB care are mediated by individual and health facility factors. Population-based interventions that seek to reduce TB stigma and raise awareness about the benefits of early diagnosis and prompt treatment are needed. Policies that remove patients' financial barriers in access to TB care, and integration of the informal care sector into TB control in urban and rural settings are central factors in TB control.
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Oduwole, Elizabeth O. "Generation of a database of mass spectra patterns of selected Mycobacterium species using MALDI-ToF mass spectrometry." Thesis, Stellenbosch : Stellenbosch University, 2008. http://hdl.handle.net/10019.1/2838.

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Thesis (MScMedSc (Pathology. Medical Microbiology))--Stellenbosch University, 2008.
The genus Mycobacterium is a group of acid–fast, aerobic, slow- growing organisms which include more than 90 different species. A member of this genus, Mycobacterium tuberculosis, belonging to the Mycobacterium tuberculosis complex (MTB), is the causative agent of tuberculosis (TB). This disease is currently considered a global emergency, with more than 2 million deaths and over 8 million new cases annually. TB is the world’s second most common cause of death after HIV/AIDS. About one-third of the world’s population is estimated to be infected with TB. This catastrophic situation is further compounded by the emergence of Multi Drug Resistant tuberculosis (MDR-TB) and in more recent times, Extensive Drug Resistant tuberculosis (XDR-TB). Early diagnosis is critical to the successful management of patients as it allows informed use of chemotherapy. Also, early diagnosis is also of great importance if the menace of MDR-TB and XDR-TB is to be curbed and controlled. As MTB is highly infectious for humans, it is of paramount importance that TB be diagnosed as early as possible to stop the spread of the disease. Traditional conventional laboratory procedures involving microscopy, culture and sensitivity tests may require turnaround times of 3-4 weeks or longer. Tremendous technological advancement over the years such as the advent of automated liquid culture systems like the BACTEC® 960 and the MGITTM Tube system, and the development of a myriad of molecular techniques most of which involves nucleic acid amplification (NAA) for the rapid identification of mycobacterial isolates from cultures or even directly from clinical specimens have contributed immensely to the early diagnosis of tuberculosis. Most of these NAA tests are nevertheless fraught with various limitations, thus the search for a rapid, sensitive and specific way of diagnosing tuberculosis is still an active area of research. The search has expanded to areas that would otherwise not have been considered ‘conventional’ in diagnostic mycobacteriology. One of such areas is mass spectrometry. This study joins the relatively few studies of its kind encountered in available literature to establish the ground work for the application of mass spectrometry, specifically Matrix Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry (MALDI-ToF MS) in the field of diagnostic mycobacteriology. This is an area which is in need of the speed, sensitivity and specificity that MALDI-ToF technique promises to offer. Since this technology is still in its infancy, the use of utmost care in the preparation of reagents, and the handling and storage of the organisms used to generate reference mass spectra for the database cannot be overemphasized. Similarly, the optimization of certain crucial experimental factors such as inactivating method and choice of matrix is of paramount importance. The main aim of this thesis was to generate a database of reference mass spectra fingerprints of selected (repository) Mycobacterium species. This necessitated the standardization of an experimental protocol which ensured that experimental factors and the various instrument parameters were optimized for maximum spectra generation and reproducibility. A standard operating procedure (SOP) for generating the database of reference mass spectra finger print of selected Mycobacterium species was developed and used to investigate the ability of the database to differentiate between species belonging to the same clinical disease complex as well as the nontuberculosis complex. The findings of this study imply that if the defined protocol is followed, the database generated has the potential to routinely identify and differentiate (under experimental conditions) more species of Mycobacterium than is currently practical using PCR and its related techniques. It is therefore a realistic expectation that when the database is clinically validated and tested in the next phase of the study, it will contribute immensely to the diagnosis of tuberculosis and other mycobacterioses. It will also aid in the identification of emerging pathogens particularly amongst the non-tuberculous mycobacteria.
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Adams, Shahieda. "A study to evaluate immunodiagnostic tests for tuberculosis infection and determinants of TB infection in a population of health care workers in the Western Cape of South Africa." Doctoral thesis, University of Cape Town, 2015. http://hdl.handle.net/11427/15468.

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Includes bibliographical references
Background: Health care workers are at increased risk of acquiring latent tuberculosis infection (LTBI). The emergence of interferon - gamma release assays (IGRAs) for the diagnosis of LTBI, presents an opportunity for improved estimation of TB infection prevalence and incidence. Their utility in settings with high background prevalence TB and HIV infection is unknown. Major aims of the study were to: * Evaluate the prevalence and factors associated with TB infection using both tuberculin skin test (TST) and IGRA assays in a sample of health care workers. * Evaluate change in interval test response over one year to determine annual risk of infection and determinants associated with test conversion. Methods: Participants completed a questionnaire on occupational and environmental characteristics including a TB symptom screen and underwent chest radiograph and rapid HIV test. Three tests for latent TB infection were administered: TST, QuantiFERON - TB Gold In - Tube (QFT - GIT) and a T - SPOT.TB test. All tests were repeated one year later. Results: The prevalence of TB infection at baseline was 84%, 65% and 60% as measured by TST, QFT - GIT and T - SPOT.TB. There was only fair agreement between TST and IGRAs. HIV positive status was significantly associated with having a TST negative / T - SPOT.TB positive discordant test response (OR=4.72). TST had superior sensitivity than IGRAs for the diagnosis of LTBI. In primary level staff a positive TST outcome, was negatively associated with HIV positive status (OR=0.41). Long employment duration was positively associated with TST (OR=4.17) and QFT - GIT (OR= 2.42) positivity. Involvement in sputum collection (OR=3.25) and home - based care of TB patients (OR= 4.14) was associated with a positive IGRA test. The conversion rate for TST and IGRAs was 38% and 22%, respectively. Reversion rates ranged from 1 % - 16 % and was lowest for TST. Factors associated with conversion (for IGRAs) included employment sector, counselling of TB patients and a baseline positive TST. Conclusion: The annual rate of TB infection was very high pointing to occupational exposure as a contributory factor. TST had superior sensitivity than IGRAs for LTBI diagnosis but poor uptake on serial testing. IGRAs had excellent uptake but its clinical utility was negatively influenced by high rates of reversion.
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13

Kanene, Cuthbert. "Assessment of the coverage and quality of HIV diagnosis, prevention and care activities within the TB programme in Livingstone District, Zambia." Thesis, University of the Western Cape, 2012. http://hdl.handle.net/11394/4506.

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Magister Public Health - MPH
In recognition of high dual burden of tuberculosis (TB) and Human Immunodeficiency virus(HIV) in Sub-Saharan Africa, the World Health Organization (WHO, 2004) provided guidance for implementing integrated HIV/TB services. This strategy has been implemented using different models ranging from partial to fully integrating, and evaluations of these models have been conducted to determine their effectiveness. The aim of this study was to describe and contrast the effectiveness of different models of implementation of HIV and TB integration at primary care level within the Tuberculosis (TB) programme in Livingstone District, Zambia The specific objectives of the study included; 1. To describe the models of integrated HIV and TB services that are currently implemented at four health facilities within the TB programme in Livingstone District at primary health care level. 2. To describe and contrast the coverage and quality of HIV diagnosis in the Tuberculosis(TB) programme achieved in the different facilities representing fully and partially integrated models of service delivery. 3. To describe and contrast the coverage and quality of HIV prevention activities in the Tuberculosis (TB) programme achieved in the different health facilities representing fully and partially integrated models of service delivery. 4. To describe and contrast the coverage and quality of HIV care activities received by coinfected clients in the Tuberculosis (TB) programme in the different facilities representing fully and partially integrated models of service delivery. 5. To describe the quality and outcomes of TB diagnosis and treatment in the different facilities representing fully and partially integrated models of service delivery. A research design using quantitative methodologies: a cross sectional survey and structured observations or review of patient records (quantitative) were used. The records of 814 TB clients notified in 2010 served as the study population while the sample of 464 (232 from partially and 232 from fully integrated) were randomly selected. Two data collection tools namely: patient record and HIV/TB register review; facility staff interviews (key informant interviews) were used and the results were analyzed using Epi info statistical package. In the study, all respondents gave informed consent and no personal information was collected from the retrospective record review. The HIV prevention interventions in this study were rated below 30% except for of HIV education (97%). Statistically significant differences (p-value<0.001) existed for condom provision at facility level. Poor performance reported for STI screening (below 2%) and PMTCT information (below 15%). The HIV testing rate was 94% among TB clients which was higher than the counseling coverage of 88%. Statistically significant differences (p value <0.001) at facility level existed for clients who received HIV test results. Sixty three percent (63%) of TB clients were also co- infected with HIV. ART assessment for TB clients was below 40% and statistically significant differences (p value=<0.001) between facilities were identified for this indicator. ART assessment of TB clients at the same facility they tested for HIV was above 50% for all facilities. The continuation of cotrimoxazole was poor at 38% and statistically significant differences (p value=<0.001) were identified for this indicator between facilities. Sputum testing was 85% while the cure rate was poor at 28% average for all facilities. Statistically significant differences (p-<0.001) were noticed at model level for clients cured. Although HIV prevention and care services were introduced in the TB program in Livingstone,they were not comprehensive enough to respond to the high HIV and TB co-infectivity. For HIV prevention, other than HCT and HIV education, the rest of the critical interventions such as condom provision, STI screening and treatment, and PMTCT intervention were neglected. The HIV care services such as ART assessment and CPT implementation were also poor. There is need to put in place systems to improve these services in the district to improve treatment outcomes. The differences that were noted in performance for the majority of the indicators were mainly at facility level as being a fully integrated facility did not guarantee effective integration or better performance.
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14

Shanaube, Kwame, James Hargreaves, Katherine Fielding, Ab Schaap, Katherine-Anne Lawrence, Bernadette Hensen, Charalambos Sismanidis, et al. "Risk factors associated with positive quantiFERON-TB gold in-tube and tuberculin skin tests results in Zambia and South Africa." Public Library of Science (PLOS), 2011. http://hdl.handle.net/10019.1/11596.

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The original publication is available at http:/www.plosone.org
Introduction: The utility of T-cell based interferon-gamma release assays for the diagnosis of latent tuberculosis infection remains unclear in settings with a high burden of tuberculosis. Objectives: To determine risk factors associated with positive QuantiFERON-TB Gold In-Tube (QFT-GIT) and tuberculin skin test (TST) results and the level of agreement between the tests; to explore the hypotheses that positivity in QFT-GIT is more related to recent infection and less affected by HIV than the TST. Methods: Adult household contacts of tuberculosis patients were invited to participate in a cross-sectional study across 24 communities in Zambia and South Africa. HIV, QFT-GIT and TST tests were done. A questionnaire was used to assess risk factors. Results: A total of 2,220 contacts were seen. 1,803 individuals had interpretable results for both tests, 1,147 (63.6%) were QFT-GIT positive while 725 (40.2%) were TST positive. Agreement between the tests was low (kappa = 0.24). QFT-GIT and TST results were associated with increasing age (adjusted OR [aOR] for each 10 year increase for QFT-GIT 1.15; 95% CI: 1.06-1.25, and for TST aOR: 1.10; 95% CI 1.01-1.20). HIV positivity was less common among those with positive results on QFT-GIT (aOR: 0.51; 95% CI: 0.39-0.67) and TST (aOR: 0.61; 95% CI: 0.46-0.82). Smear positivity of the index case was associated with QFT-GIT (aOR: 1.25; 95% CI: 0.90-1.74) and TST (aOR: 1.39; 95% CI: 0.98-1.98) results. We found little evidence in our data to support our hypotheses. Conclusion: QFT-GIT may not be more sensitive than the TST to detect risk factors associated with tuberculous infection. We found little evidence to support the hypotheses that positivity in QFT-GIT is more related to recent infection and less affected by HIV than the TST. © 2011 Shanaube et al.
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15

Owolabi, Rotimi Samuel. "Optimizing the diagnosis and management of tuberculosis and assessing the burden of hypertension among HIV patients in a high TB and HIV burden setting." Thesis, University of Liverpool, 2018. http://livrepository.liverpool.ac.uk/3027599/.

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Background: TB is the commonest cause of death among people living with HIV (PLHIV) in Nigeria. It is difficult to diagnose TB among PLHIV and diagnosed patients often experience poor treatment outcome. Although, PLHIV are living longer because of increased access to antiretroviral therapy (ART), hypertension is emerging as a major co-morbidity in this population. This study explored better means of diagnosing TB among individuals with and without HIV, described TB treatment outcomes and their determinants, and assessed the burden of hypertension among PLHIV. Methods: This thesis comprises four studies conducted in University of Abuja Teaching Hospital (UATH): one cross-sectional study of PLHIV to assess the performance of the WHO TB symptom screening algorithm; a prospective study to evaluate whether C-reactive protein (CRP) and Interferon gamma-inducible protein 10 (IP-10) could be used to screen individuals for TB; a retrospective study to describe the TB treatment outcome of PLHIV and HIV-negative patients and the risk factors for poor treatment outcome and a retrospective study to describe the prevalence and incidence of hypertension and its determinants among PLHIV registered over a period of 3 years. Results: 202 PLHIV were screened for TB and 72.3% had symptoms of TB. However, only 3% and 6.5% had culture or culture plus smear confirmed TB, respectively. The WHO algorithm had 83.3% sensitivity, 29.1% specificity and 98.2% negative predictive value. CRP and IP-10 were measured in 408 patients with TB symptoms, of which, 21% had culture-confirmed TB. CRP had 91.4% and 33.2% sensitivity/specificity among all participants, 95.3% and 42.6% among HIV-negative patients, and 84.8% and 22.1% sensitivity/specificity among PLHIV, respectively. IP-10 had 87.3% and 40.9% sensitivity/specificity among all participants and 87.5% and 50.3% among HIV-negative and 79.4% and 47.2% among PLHIV, respectively. 998 patients were treated for TB by the hospital in the last 5 years. Of these, 62% had treatment success, 8.4% died and 18% were lost-to-follow up (LTFU). TB/HIV-coinfection rate was 44.3%. Treatment success was 52.3% among PLHIV and 70% among HIV-negative patients (p = 0.001) with higher deaths (15.5% versus 2.9%, p = 0.001) and LTFU (22.5% versus 14.3%, p = 0.001) among PLHIV. Poor treatment outcome and LTFU were more frequent among older individuals, PLHIV, those without sputum smear results and low body weight. Low weight and not receiving Co-trimoxazole were associated with poor outcome and LTFU among PLHIV. 12.8% of 883 PLHIV had hypertension at enrolment and 11.2% developed hypertension 12 months after enrolment. Hypertension was associated with older age, higher BMI, hepatitis B and higher CD4 counts. Patients with incident hypertension had higher systolic and diastolic blood pressure on enrolment. Conclusion: The WHO TB screening algorithm performed as reported by WHO. However, most patients had symptoms of TB and required further tests, which limits its efficiency in high burden settings. CRP performed better than IP-10 and both markers performed better in HIV-negative than among PLHIV. TB treatment outcome was poor and was worse among PLHIV. Hypertension is a common problem among PLHIV. There is a need for better screening tools for TB among HIV-positive patients and to develop interventions to improve the outcome of patients with TB, especially among the elderly, PLHIV and those presenting with underweight. The high burden of hypertension among HIV patients signals the need to integrate care of hypertension and other noncommunicable diseases into HIV care programs.
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16

Fisher, Julian Marcus. "A study at the Brooklyn Chest Hospital to assess the change in the oral carriage of Candida species in patients co-infected with HIV and TB, before and after antifungal therapy." Thesis, Stellenbosch : Stellenbosch University, 2002. http://hdl.handle.net/10019.1/52706.

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Thesis (MSc)--Stellenbosch University, 2002.
ENGLISH ABSTRACT: The aim of this study at the Brooklyn Chest Hospital (BCH) was to assess the change in the oral carriage of Candida species in twenty-nine patients co-infected with the Human Immunodeficiency Virus (HIV) and Tuberculosis (TB), before and after anti-fungal treatment. Each patient accepted onto the study underwent a comprehensive oral and peri-oral examination where the presence, site and clinical features of all oral and peri-oral lesions were recorded. The purpose of the examination was to provide a clinical diagnosis of oral candidasis. Each patient was also asked to provide a sample of oral fluid for laboratory analysis. This was collected using an oral rinse. The results of a variety of laboratory investigations were used to identify the species of Candida obtained from the oral rinse. Both the oral and peri-oral examination and the oral rinse procedure were repeated after one month and at three months. A sample from each oral rinse was inoculated on CHROMagar Candida chromogenic medium (CHROMagar Candida, France, Paris). CHROMagar is used for the isolation and presumptive identification of Candida sp. from other yeasts on the basis of strongly contrasted colony colours, which are produced by the reactions of species-specific enzymes with a proprietary chromogenic substrate. After forty-eight hours the CHROMagar plate was examined for growth, when a record of colony morphology and colour was made. A single sample from each different colour-coded colony was taken and streaked onto a Sabouraud plate (Oxoid, Basingstake, England) and then incubated for forty eight hours at thirty-seven degrees centigrade. A variety of laboratory investigations were subsequently carried out on a single colony taken from the Sabouraud agar plate (Oxoid). The results of these tests were used to identify the individual species of Candida isolated from each oral rinse. Oral candidasis was the most prevalent oral lesion observed on admission and at three months. Six different species of Candida were identified during this study, namely Candida albicans, Candida dubliniensis, Candida krusei, Candida glabrata, Candida parapsilosis, and Candida tropicalis. C.albicans was the most commonly identified species in study population. Candida dubliniensis was isolated and identified for the first time in a South African HIV population. Each specimen of Candida sp. identified by laboratory analysis was tested for sensitivity to Nystatin, Amphotericin B and Fluconazole anti-fungal agents. An additional sensitivity test was performed using Ajoene and Allicin (extracts of garlic) to assess the comparative antifungal properties of these compounds.
AFRIKAANSE OPSOMMING: Die doelwit van hierdie studie by die Brooklyn Borshospitaal (BCH) was om die verandering in orale draerstatus van die Kandida spesies in nege-en-twintig HIVfTB koïnfekteerde pasiënte vas te stel, voor- en na antifungale behandeling. Elke pasiënt in die studie het 'n volledige intra- en ekstra-orale ondersoek ondergaan. Die teenwoordigheid, area en kliniese voorkoms van alle letsels is noteer. Die doel van die ondersoek was om 'n kliniese diagnose van orale kandidiase te verkry. 'n Monster orale vloeistof is geneem van elke pasiënt vir laboratorium analise. Die monster is in die vorm van 'n mondspoel geneem. Verskeie toetse is gedoen om die verskillende Kandida spesies in elke monster te identifiseer. Die orale- en ekstra-orale ondersoek sowel as die mondspoelmonster is na 1 en 3 maande herhaal. Elke mondspoelmonster is op CHROMagar Kandida chromogene medium (CHROMagar Candida, France) inokuleer. CHROMagar word gebruik vir die vermoedelike identifikasie en isolasie van Kandida spesies teenoor ander swamme. Dit word gedoen op die basis van kontrasterende koloniekleure, wat teweeggebring word deur spesie-spesifieke ensiemreaksies op 'n chromogene substraat. Die CHROMagar plate is na 48 uur ondersoek vir groei en die kolonie-morfologie en - kleur is noteer. 'n Enkel monster. is geneem van elke verskillende kolonie (geskei op kleur) en is uitgestreep op 'n Saboraud plaat (Oxoid, Basingstoke, England). Dit is dan vir 48 uur inkubeer teen 37°C. Verskeie laboratorium ondersoeke is daarna uitgevoer op 'n enkel kolonie geneem vanaf die Saboraud agar plaat (oxoid). Die resultate van die ondersoeke is gebruik om individuele spesies van Kandida te identifiseer. Orale Kandidiase was die mees algemene orale letsel geïdentifiseer by toelating en 3 maande ondersoeke. Ses verskillende spesies Kandida is identifiseer tydens die studie, naamlik: Kandida albicans, K.dubliniensis, K.Krusei, K.glabrata, K.parapsilosis en K.tropicalis. K.albicans was die mees algemeen identifiseerde spesie in die studiepopulasie. K.dubliniensis is vir die eerste keer in Suid-Afrika in 'n HIV<+lpopulasie isoleer en geïdentifiseer. Elke monster van identifiseerde Kandida spesies is getoets vir sensitiwiteit teenoor Nistatien, Amfotensien B en Flukonasool. Addisioneel is ook getoets vir sensitiwiteit teenoor Ajoene en Allicin (knoffelekstrakte).
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17

Menezes, Angela Maria. "Utilization of antigen-specific host responses in the evaluation of Mycobacterium tuberculosis infection, development of disease and treatment effect." Thesis, Stellenbosch : Stellenbosch University, 2013. http://hdl.handle.net/10019.1/79850.

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Thesis (MScMedSc)--Stellenbosch University, 2013.
ENGLISH ABSTRACT: Setting This study was conducted in the Tygerberg district, Cape Town, in the Western Cape, South Africa Background The evaluation of early tuberculosis (TB) treatment response is based on month 2 sputum culture status. This method of evaluation has a number of limitations: the test requires relatively advanced laboratory infrastructure and procedures, it takes several weeks to obtain results and is a relatively a poor marker at predicting treatment response. The discovery of potential host markers which reflect the efficacy of early treatment would be of great importance for clinical management of individual patients. The treatment failure would be detectable earlier than at week 8 of treatment. The duration of clinical trials of new anti-tuberculosis drugs may also be substantially reduced by such markers if these would be measurable earlier than at week 8 of therapy. Objectives 1) To evaluate diluted, 7-day whole blood cultures stimulated with live Mycobacterium tuberculosis (M.tb) for the presence of host markers of early TB treatment response 2) To evaluate an overnight, undiluted, M.tb antigen stimulated whole blood culture Quantiferon Gold In Tube (QFT-GIT) supernatants for host markers of early TB treatment response The study designs were as follows: In study one, baseline samples and samples from week 1, week 2 and week 4 of treatment from 30 cured TB patients were selected from a larger biomarker study, in which whole blood was stimulated with live M.tb or left unstimulated. Fifty seven host markers were measured in supernatants by multiplex cytokine arrays. In study two, baseline samples and samples from week 2 and week 8 of treatment from 19 cured TB patients were randomly selected from the placebo group in a micronutrient supplement study. QFT-GIT supernatants from these participants were assessed through multiplex cytokine arrays for levels of fifty seven host markers. All of the participants in both studies were Human Immunodeficiency Virus (HIV) negative. Changes in marker expression over time and between fast and slow responders to treatment were evaluated. Comparability between the two culture methods was assessed for markers that were evaluated in both studies. Results In study one, the majority of host markers showed significant changes over time in the unstimulated supernatants. Only GRO and IL-1beta changed significantly in an antigen-specific manner (background levels subtracted). No significant changes were observed between fast and slow responders. In study two, the majority of host markers showed significant changes over time in the unstimulated supernatants whereas only MDC and IL-4 changed during the observation period in antigen stimulated levels. Significant differences were observed between fast and slow responders at pre-treatment for IL-13 Ag-Nil and IL-1betaAg-Nil . Conclusion This study revealed, antigen-specific responses showed only limited potential for early TB treatment response monitoring, but may have potential in differentiating between treatment outcomes. Future investigations may have to include later time points during treatment as these were not included in the present assessment. The QFT-GIT samples do not appear to be equivalent to live M.tb stimulated 7-day whole blood assays.
AFRIKAANSE OPSOMMING: Instelling Die studie is uitgevoer in die Tygerbergdistrik, Kaapstad, Wes-Kaap, Suid-Afrika. Agtergrond Die evaluering van die respons op vroeë tuberkulose (TB) behandeling word gebaseer op die status van maand 2 sputum kulture. Hierdie evalueringsmetode het ‘n paar beperkinge: die toets benodig relatief gevorderde laboratorium infrastruktuur en prosedures, die toetsuitslae is eers na ‘n paar weke beskikbaar en dit is n relatiewe swak merker om repons op behandeling te voorspel. Die ontdekking van potensiële selfmerkers wat die doeltreffendheid van vroeë behandeling weerspieël sal van groot belang wees vir die kliniese bestuur van individuele pasiënte. Mislukking van die behandeling sal sodoende voor week 8 van behandeling waargeneem kan word. Die tydsduur van kliniese proewe van nuwe anti-tuberkulose medikasie mag ook baie verkort word met sulke merkers as dit voor week 8 van behandeling gemeet kan word. Doelwitte 1) Om verdunde, 7-dae oue volbloedkulture, met lewende Mikobakterium tuberkulosis (M.tb) gestimuleer, te evalueer vir die teenwoordigheid van vroeë TB behandeling respons selfmerkers. 2) Om die supernatant van oornag, onverdunde, M.tb antigeen gestimuleerde volbloedkulture Quantiferon Gold In Tube (QFT-GIT) vir vroeë behandeling respons selfmerkers te evalueer. Die studie-ontwerpe was soos volg: Met studie een is basislynmonsters en monsters verkry na week 1, week 2 en week 4 van behandeling van 30 geneesde TB-pasiënte geselekteer uit ‘n groter biomerkerstudie waarin die volbloed met lewende M.tb gestimuleer is of ongestimuleer gelaat is. Sewe-en-vyftig selfmerkers is in die supernatante gemeet deur middel van multipleks sitokine arrays. Met studie twee is basislynmonsters en monsters verkry na week 2 en week 8 van behandeling van 19 geneesde TB-pasiënte lukraak uit die plasebo-groep in ‘n mikrovoedingstowwe-aanvullingstudie geselekteer. Vlakke van 57 selfmerkers is in die QFT-GIT supernatante van hierdie deelnemers, deur middel van die multipleks sitokine arrays, bepaal. Al die deelnemers van beide studies was HIV negatief. Veranderinge in merker-uitdrukking oor tyd, asook tussen vinnige en stadige respons tot behandeling, is ge-evalueer. Die vergelykbaarheid van die twee kultuurmetodes is geassesseer ten opsigte van die ge-evalueerde merkers in albei studies. Resultate Met studie een het die meerderheid van die selfmerkers in die ongestimuleerde supernatante kenmerkende verandering oor tyd gewys. Slegs GRO en IL-1beta het aansienlik verander in die antigeenspesifieke wyse (agtergrond vlakke afgetrek). Geen kenmerkende veranderinge was waargeneem tussen die vinnige en stadige respons pasiënte nie. Met studie twee het die meerderheid van die selfmerkers aansienlike veranderinge oor tyd in die ongestimuleerde supernatante gewys, in vergelyking waar net die MDC en IL-4 veranderinge gedurende die observasie periode in antigeen gestimuleerde vlakke getoon het. Kenmerkende verskille is tussen die vinnige en stadige respons pasiënte in voorbehandeling vir IL-13 Ag-Nil en IL-1betaAg-Nil waargeneem. Gevolgtrekking Die studie bewys dat antigeenspesifieke response slegs beperkte potensiaal vir vroeë TB behandeling respons monitering het, maar mag die potensiaall vir onderskeidende behandeling uitkomste hê. Toekomstige ondersoeke sal dalk latere tydpunte gedurende die behandeling moet insluit aangesien dit nie in hierdie evaluasie ingesluit is nie. Die QFT-IT monsters verskyn nie as gelykwaardig met die lewendig M.tb gestimuleerde 7-dae volbloed toetse nie.
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18

Hoek, Kim Gilberte Pauline. "Investigation into genotypic diagnostics for mycobacterium tuberculosis." Thesis, Stellenbosch : Stellenbosch University, 2010. http://hdl.handle.net/10019.1/5479.

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Thesis (PhD )--University of Stellenbosch, 2010.
ENGLISH ABSTRACT: Diagnostic delay is regarded as a major contributor to the continuous rise in tuberculosis (TB) cases and the emergence and transmission of multidrug-resistant tuberculosis (MDR-TB) and extensively drug resistant tuberculosis (XDR-TB). It is therefore essential that more rapid diagnostic methods are developed. Molecular-based assays have the potential for the rapid species-specific diagnosis of TB and associated drug-resistances directly from clinical specimens. We investigated whether high resolution melting analysis (HRM) could enable the rapid diagnosis of TB and associated drug resistance, since the HRM apparatus and reagents are relatively inexpensive and the methodology can easily be implemented in high incidence, low income regions. Application of this methodology allowed for the rapid identification of mycobacterial lymphadenitis from fine-needle aspiration biopsy (FNAB) samples in 2 studies. This was done by targeting the region of deletion 9 (RD9), present in M. tuberculosis and M. canettii, but absent from all other members of the complex. However, the sensitivity of the method was low (51.9% and 46.3%, respectively) when compared to the reference standard (positive cytology and/or positive culture). Despite this limitation our method was able to provide a rapid diagnosis in more than half of the infected patients with a relatively high specificity (94.0% and 83.3%, respectively). We therefore proposed a diagnostic algorithm allowing the early treatment of patients with both HRM and cytology results indicative of mycobacterial disease. We developed the Fluorometric Assay for Susceptibility Testing of Rifampicin (FAST-Rif) which allowed the rapid diagnosis of MDR-TB by detecting rifampicin (RIF) resistance mutations in the rpoB gene with a sensitivity and specificity of 98% and 100%, respectively. The FAST-Rif method was easily adapted to detect ethambutol (EMB) resistance due to mutations in the embB gene with a sensitivity and specificity of 94.4% and 98.4% respectively, as compared to DNA sequencing. The FAST-EMB method was a significant improvement over the inaccurate culture based method. We identified a strong association between EMB resistance (and pyrazinamide resistance) and MDR-TB and subsequently advised modifications to the current (2008) South African National TB Control Programme draft policy guidelines. Due to the potential for amplicon release, we adapted the FAST-Rif and FAST-EMB methods to a closed-tube one-step method using the detection of inhA promoter mutations conferring isoniazid (INH) resistance as a model. The method (FASTest-inhA) was able to identify inhA promoter mutations with a sensitivity and specificity of 100% and 83.3%. These mutations are of particular interest as they confer low level INH resistance and cross-resistance to ethionamide (Eto). Since inhA promoter mutations are strongly associated with XDR-TB in the Western and Eastern Cape Provinces of South Africa, data generated by the recently implemented GenoType® MDRTBPlus assay may allow individualised treatment regimens to be designed for a patient depending on their INH mutation profile. Our proposed treatment algorithm may be particularly useful in XDR-TB cases, for which only few active drugs remain available. Since current diagnostic methods all carry advantages and disadvantages, a combination of phenotypic and genotypic-based methodologies may be the best scenario while awaiting superior methods.
AFRIKAANSE OPSOMMING: Die onvermoë om tuberkulose (TB), multi-weerstandige tuberkulose (MDR-TB) en uiters weerstandige tuberkulose (XDR-TB) vinnig te diagnoseer, is ‘n belangrike oorsaak vir die volgehoue toename en verspreiding daarvan. Dit is noodsaaklik dat diagnostiese toetse wat vinniger resultate oplewer, ontwikkel word. Molukulêre toetsing het die potensiaal om vinnig spesie-spesifieke diagnoses van TB en die weerstandigheid teen TB-medikasie te lewer. Hierdie studie wil vasstel of hoë-resolusie smeltingsanalise (HRS) ‘n vinnige diagnose van TB en die weerstandigheid teen TB-medikasie kan oplewer aangesien die relatiewe lae koste van reagense en apparaat, asook die minimale infrastruktuur en vaardighede wat vir dié toets benodig word, dit uiters geskik maak vir pasiënte in gebiede met ‘n hoë TB-insidensie en lae inkomste. Die toepassing van die HRS-metode op fynnaald-aspiraatbiopsies in twee afsonderlike studies, het gelei tot die vinnige identifisering van mikrobakteriële-limfadenitis. Dit is bemiddel deur die gebied van delesie 9 (RD9) teenwoordig in Mycobacterium tuberculosis en M. canettii, maar afwesig in al die ander lede van die kompleks, te teiken. Die sensitiwiteit van die metode was (51.9% en 46.3%, vir die twee studies onderskeidelik) in vergelyking met die verwysingstandaard (positiewe sitologie en/of positiewe kultuur). Ten spyte van dié beperking was ‘n vinnige diagnose in meer as die helfte van geïnfekteerde pasiënte met ‘n redelike hoë spesifisiteit (94.0% en 83.3%, onderskeidelik) moontlik. ‘n Diagnostiese algoritme wat gebaseer is op die resultate van die HRS en sitologie-toetse, is voorgestel om pasiënte vroeër te behandel. ‘n Fluorometriese toets (FAST-Rif) is ontwikkel vir die vinnige diagnose van MDR-TB deur mutasies in die rpoB-geen op te spoor met ‘n hoë sensitiwiteit en spesifisiteit (98% en 100%, onderskeidelik). Hierdie mutasies is verantwoordelik vir weerstandigheid teen die antibiotikum rifampicin (FAST-Rif) en word beskou as ‘n vinnige diagnose vir MDR-TB. Die FAST-Rif metode kon maklik aangepas word om mutasies in die embB-gene, verantwoordelik vir weerstandigheid teen die antibiotikum ethambutol (EMB), op te spoor. Die FAST-EMB-metode het ‘n sensitiwiteit en spesifisiteit van 94.4% en 98.4% onderskeidelik getoon in vergelyking met DNS volgordebepaling. Die FAST-EMB-metode was ‘n betekenisvolle verbetering op die onakkurate kultuurgebaseerde metodes. ‘n Sterk korrelasie tussen EMB-weerstandigheid (en weerstandigheid teen pyrazinamide) en MDR-TB is geïdentifiseer. Vervolgens is veranderinge aan die Suid-Afrikaanse Nasionale TB-beheerprogram se Konsepbeleidsgids (2008) voorgestel. Om die potensiële vrylating van amplikone te verhoed, is die FAST-Rif en FAST-EMB aangepas tot ‘n enkelstap geslote buissisteem deur gebruik te maak van die opsporing van inhA promotormutasies wat weerstandigheid teen isoniazid (INH) veroorsaak. Die metode het ‘n sensitiwiteit en spesifisiteit van 100% en 83.3% onderskeidelik, getoon. Hierdie mutasies veroorsaak laevlak weerstandigheid teen INH, maar ook kruisweerstandigheid teen ethionamide (Eto). Aangesien daar ‘n sterk verbintenis tussen inhA-promotormutasies en XDR-TB in die Oos en Wes-Kaapprovinsies van Suid-Afrika is, kan data van die GenoType® MDRTBPlus-toets moontlik gebruik word om ‘n meer geïndividualiseerde behandeling te ontwerp afhangende van die pasiënt se INH-mutasieprofiel. Ons behandelingsalgoritme is veral geskik vir XDR-TB pasiënte vir wie daar weinig aktiewe antibiotika beskikbaar is. Huidige diagnostiese metodes het almal voor- en nadele, dus bied ‘n kombinasie van fenotipiese en genotipiese metodes moontlik die beste oplossing totdat beter metodes ontwikkel word.
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Ali, Hanan M. "Development of new diagnostic devices for TB." Thesis, Bangor University, 2015. https://research.bangor.ac.uk/portal/en/theses/development-of-new-diagnostic-devices-for-tb(5a962fb1-76f7-45ec-b9d6-4b7e30749136).html.

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The main objective of the work was to develop an analytical method for the diagnosis of human and bovine TB+ and para-TB by finding the best Ag with high Ab binding signal. This was achieved in five parts. First, the synthesis of S,S-trans-alkene-methoxy mycolic acid (I) from M. tb was achieved successfully. This led to the synthesis of its glycolipid derivatives (TDM, TMM, GroMM, GMM and ArM). The second part was the analysis of a range of other synthetic Ags using TB+ and TB- human serum samples in ELISA assays. The best combinations of sensitivity and specificity were observed with TDM (160) (100 and 78%), ArM (179) (100 and 73%) and ArM (158) (100 and 86%). Combining the results from synthetic TDM (160), ArM (158) and GMM (180) gave 100 and 94% sensitivity and specificity. These represent very much better values than those reported with many recognised assays. The third part involved the serodiagnostic evaluation of the sugar esters of MA (I). High biological activity was observed with TDM (44). This also gave high distinction between TB+ and TB- human serum samples, the best combinations of sensitivity and specificity (100, 73%) and high area under the ROC curve (0.929) in contrast with other derivatives. The fourth part achived using four different sets of bovine serum samples, including one set of animals diagnosed with active bTB. Statistical analysis using multidimensional scaling (MDS) analysis and the Random Forest (RF) analysis showed that the ELISA assay can distinguish between different categories of serum sample. Combining the results from a set of Ags using mean decrease accuracy and mean decrease Gini illustrated that the synthetic Ags gave responses higher than the natural Ags. The best area under the ROC curves, sensitivity and specificity were observed with TDM (156) 0.959, 100 and 86 % respectively. Finally, a range of antigens were studied in ELISA assays using serum from cattle infected with MAP.
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Werely, Cedric J. "Pharmacogenetics of Arylamine N-acetyltransferase genes in South African populations." Thesis, Stellenbosch : Stellenbosch University, 2012. http://hdl.handle.net/10019.1/71832.

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Thesis (PhD)--Stellenbosch University, 2012.
Includes bibliography
ENGLISH ABSTRACT: Tuberculosis (TB) has been declared a global health emergency by the World Health Organisation, and consequently there is an urgency to develop improved methods of diagnosis and treatment. Despite the current TB epidemic, the disease can be treated effectively using isoniazid (INH) in combination with other antibiotics. However, INH is inactivated in the body by certain drug metabolising enzymes, which may reduce the efficacy of TB treatment. The activity of these drug metabolising enzymes, called NAT, are in turn reduced by nucleotide changes (SNPs) in the gene. These genetic variants (alleles) have been correlated with the rapid- (FA), intermediate- (IA), and slow acetylation (SA) enzymatic activity, and one is therefore able to investigate potential phenotypic effects via genotypic analyses. We investigated these genetic changes in the NAT1 and NAT2 genes in individuals from the local Coloured community (SAC) since this group has one of the highest TB incidences in the country. NAT2 is primarily responsible for the inactivation of INH, whilst NAT1 metabolises para-aminosalicyclic acid (PAS) which is used in the treatment of drug resistant TB. The NAT2 results indicated that the NAT2 alleles were not equally represented in three local ethnic groups studied, and subsequently the rapid, intermediate and slow acetylation activity reflected these differences. However, the relative frequency of these variants in the SAC and Caucasian groups were relatively low. These differences require further investigation to determine their overall relevance to the NAT2 activity differences between groups. In the case of the NAT1 analysis we also observed differences in the relative frequency of various NAT1 alleles between Caucasian and SAC individuals. However, many of these NAT1 SNPs and alleles have not as yet been characterised, so effects of these variants are currently unknown. Interestingly, the NAT1*4 and NAT1*10 alleles were the most prevalent NAT1 alleles in both Caucasians and SAC. The NAT1*4 allele exhibits the rapid NAT1 activity, whilst the activity of the NAT1*10 allele is currently subject to ongoing debate. In this respect, the analysis of NAT1 continues to be a topic for ongoing research. These results, observed for the NAT genes, underscore the importance of doing genetic analyses in local ethnic groups, since these differences may vary significantly between the groups.
AFRIKAANSE OPSOMMING: Tuberkulose (TB) is deur die Wêreldgesondheidsorganisasie (WGO) tot 'n globale gesondheidsnood verklaar en derhalwe is dit noodsaaklik dat nuwe, verbeterde diagnostiese metodes ontwikkel word, wat tot meer effektiewe behandeling kan lei. Ten spyte van die huidige TB-epidemie, kan die siekte doeltreffend behandel word deur middel van isoniasied (INH), in kombinasie te met ander antibiotika. INH kan egter geïnaktiveer word deur sekere ensieme in die liggaam, met die gevolg dat INH nie meer effektief is nie in die behandeling van TB. Die aktiwiteit van hierdie ensiem, die sogenaamde NAT2 (Arielamien N-asetieltransferase 2) ensiem, word op sy beurt beïnvloed deur sekere nukleotied veranderings (SNPs) in die geen. Hierdie genetiese veranderings gekorreleer met ensiemaktiwiteitsveranderings (geklassifiseer as vinnig (FA) Intermediêr (IA) en stadig (SA)), wat mens in staat stel om potensiële fenotipiese effekte te ondersoek deur middel van genotipiese analise. Ons het hierdie genetiese veranderings ondersoek in die NAT1 en NAT2 gene in individue van die Kleurling-gemeenskap (SAC) omdat díe bevolkingsgroep die hoogste voorkoms van TB in die land het. NAT2 is primêr verantwoordelik vir die inaktivering van INH, terwyl NAT1 para-amienosalisilaat (PAS) inaktiveer, wat gebruik word in die behandeling van midel-weerstandige TB. Die NAT2 resultate dui daarop dat die allele van die NAT2 geen nie eweredig verteenwoordig wasin die drie etniese groepe nie en derhalwe word die vinnige (FA), intermediêre (IA) en stadige (SA) ensiemaktiwiteite deur hierdie verskille weerspieël. Hoewel die teenwoordigheid van hierdie variante relatief laag was in die SAC en Koukasiër gemeenskappe, is verdere studies nodig om die omvang van hierdie verskille te bepaal ten onsigte van NAT2 aktiwiteit tussen groepe. In die geval van die NAT1 analise het ons verskille waargeneem in die voorkoms van verskeie NAT1 allele tussen Koukasiese en SAC individue. Baie van hierdie NAT1 SNPs is egter nog nie gekarakteriseer nie, en derhalwe is die effek van hierdie NAT1 variante onbekend. Die NAT1*4 en NAT1*10 allele was die prominentste NAT1 alleel in beide Koukasiërs en SAC. Die NAT1*4 is betrokke by vinnige NAT1 aktiwiteit, terwyl die effek van die NAT1*10 alleel nog onderhewig is aan aktiefwe debat. In hierdie verband, is die studie van NAT1 steeds 'n onderwerp vir toekomstige navorsing. Hierdie resultate, wat vir die NAT gene waargeneem is, beklemtoon die belangrikheid van verdere genetiese analises in plaaslike etniese groepe, aangesien hierdie verskille beduidend kan wees tussen die verskillende groepe.
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Maserumule, Matsopiane Charlotte. "The development of aptamer-based probes for the detection of TB antigens ESAT-6.CFP-10 potential TB diagnostic tools." Master's thesis, University of Cape Town, 2013. http://hdl.handle.net/11427/3425.

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Includes abstract.
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Lack of point-of-care (PoC) diagnostic tools for TB hinders control of the disease, particularly in resource-limited, high HIV and TB prevalence countries. Therefore, there is a need for simple, rapid, accurate, and affordable PoC diagnostics to detect active TB early enough for opportune intervention. To develop TB detection probes that will constitute such diagnostics, our research group recently isolated DNA aptamers that bind to a putative marker for active TB; the ESAT-6.CFP-10 heterodimer. Aptamers are highly specific artificial mimics of antibodies that have shown great prospects in diagnostic applications. The aim of this study was to characterise the anti-ESAT-6.CFP-10 aptamers, and to optimise them into more specific and affordable detection probes for the development of potential PoC TB diagnostic tools.
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Cuevas, Rachel Mary Anderson de. "The complexities of attending TB diagnostic services for adults in resource poor settings." Thesis, University of Liverpool, 2013. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.631727.

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Background: TB is a disease of poverty affecting disenfranchised populations. A major impediment to treatment access is the need to complete a diagnostic process that requires multiple visits to health services. An estimated one third of the cases occurring globally each year are never diagnosed. Addressing access barriers for TB diagnosis therefore is critical to increase access to treatment. Aims: The study aimed to identify economic, social and cultural barriers hindering patients with symptoms of TB from completing the diagnostic process and, by extension, accessing treatment, with a view to assessing the gains to be made through the implementation of a screening process that could complete smear microscopy on the first day of consultation. Methodology: Two large cross sectional studies were conducted among adults at first attendance for diagnosis. The first survey was conducted in Nigeria, Nepal, Ethiopia and Yemen and quantified the cost of attending diagnostic services, describing expenditure for the first and second day of attendance. Patients with expenditure ranking above the 75th centile were compared with patients with lower expenditure to identify risk factors for high expenditure. A screening score was developed by performing logistic regressions of these risk factors to identify patients with high expenditure. A second survey in Yemen and Ethiopia described adults' knowledge of services and the disease, service satisfaction and risk factors for defaulting. Further qualitative studies were then conducted in Yemen and Ethiopia comprising in depth interviews and focus group discussions with individuals who completed/did not complete the diagnostic process or who had registered/did not register for treatment. Results: The most significant expenses incurred by patients for diagnosis were for clinic fees and transport. Many factors were associated with high expenditure. The main contributors for high cost across all study settings were attending the services with company and rural residency. Costs for first and second day attendance were comparable. The score to identify patients at risk of high expenditure achieved 54% and 69% sensitivity and specificity and its performance varied across settings. Most participants (particularly women) attended the services with companions considerably increasing the cost of diagnosis. Many patients were unprepared for the duration of the diagnostic process. Women were perceived to face particular difficulties to access health services. Patients' reasons for defaulting diagnosis included the cost of the process, receiving negative smear results (especially in Yemen) or having a clear chest X-rayon the first day and receiving misleading or misinterpreting the information given by staff. In some settings patients had to pay additional unofficial fees and were often referred to private services. Patients found non-TB medication and additional tests in the private sector prohibitive. Many patients highlighted , opportunity costs for diagnosis and treatment. In Ethiopia, the lure of attending private sector services and poor staff attitude featured strongly. Conclusion: Patients in resource poor contexts face multiple barriers to attending and completing TB diagnosis. These barriers disproportionally affect women and are mediated by sociocultural norms. Although structural and health systems reform is needed to address many of these barriers, some could be resolved at local level with education, approaches that are patient-centred and respectful, free provision or clear charging policies and more flexible opening hours that minimise opportunity costs. A same day smear microscopy process could assist patients by reducing direct and opportunity costs if diagnostic services could complete the diagnostic process the same day of consultation.
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Driver, Cathryn Helena Stanford. "Synthesis of a thiolated mycolic motif for the development of novel TB diagnostics." Pretoria : [s.n.], 2009. http://upetd.up.ac.za/thesis/available/etd-06092009-191707.

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Cserhalmi, Nora. "Iscensättning av sjukdom : En performativ och bildsemiotisk studie av svenska konvalescentmotiv 1884­–1933." Thesis, Uppsala universitet, Konstvetenskapliga institutionen, 2021. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-434454.

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This thesis concerns six Swedish paintings depicting sick or convalescent individuals; Richard Bergh’s Konvalescent (unfinished, 1886), Flickan och Döden (1888), Eva Bonnier’s Magdalena (1887), Gustaf Magnusson’s Konvalescent (1933), Jenny Nyström’s Konvalescenten (1884), and Georg Pauli’s Vid sjukbädden (1885). The purpose of this study is to examine how sickness is portrayed and staged using performative theory and visual semiotics. The thesis takes into account that tuberculosis, being a widespread disease during the 18th and 19th Century, made it a topic of exploration in the contemporary art. With this as the framework the thesis examines whether or not it is possible to diagnose the depicted individuals. The results shows that sickness first and foremost is portrayed and staged in signs regarding the body: the face, the hands, and how the body is posed. Lastly, it is suggested that these artworks can be seen as cultural symbols of TB, since not being viable for a strictly medicinal diagnosis they are more the result of the contemporary need to examine TB and its effects on society and culture. The paintings becomes – such as a body is a vessel for a disease – vessels for the disease culturally speaking.
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LibÃrio, Mariana Pitombeira. "Efetividade do escore clÃnico neural TB no diagnÃstico rÃpido da tuberculose pulmonar em serviÃo de referÃncia." Universidade Federal do CearÃ, 2013. http://www.teses.ufc.br/tde_busca/arquivo.php?codArquivo=11555.

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Objetivos: Principalmente nas regiÃes com maior carga de TB no mundo, ainda existe grande demora no recebimento dos exames diagnÃsticos de TB pelos pacientes. Pesquisadores da Rede Brasileira de Tuberculose desenvolveram e avaliaram o desempenho de um teste diagnÃstico para TB pulmonar: escore clÃnico Neural TB. O objetivo desse trabalho foi avaliar a efetividade do escore clÃnico Neural TB no diagnÃstico rÃpido de tuberculose pulmonar em unidade de referÃncia. MÃtodos: Foi realizado um ensaio clÃnico pragmÃtico, que recebeu intervenÃÃo diagnÃstica na segunda metade do projeto. Foram recrutados 351 pacientes com 18 anos de idade ou mais, com suspeita de TB pulmonar e aplicado o escore clÃnico Neural TB. Na primeira fase do estudo, os pacientes seguiram a rotina do Hospital. Na segunda fase, os pacientes tinham a coleta do escarro para baciloscopia antecipada de acordo com a classificaÃÃo pelo escore clÃnico. Para comparaÃÃo entre duas subpopulaÃÃes independentes foram utilizados o teste T-Student e o teste de Mann Whitney. Os resultados foram considerados significantes para um valor de p < 0,05. Foi calculada RazÃo de prevalÃncia e intervalo de confianÃa de 95%. A concordÃncia entre Escore e diagnÃstico de TB pulmonar foi realizada pelo Ãndice de Kappa. Resultados: Quando comparado ao diagnÃstico realizado atravÃs da baciloscopia do escarro, cultura do escarro ou diagnÃstico clÃnico-radiolÃgico em conjunto, o escore clÃnico Neural TB apresentou sensibilidade de 75,9%, especificidade de 48,8% e acurÃcia de 55%. O uso do escore clÃnico Neural TB foi capaz de diminuir o tempo entre a triagem e a leitura da lÃmina por baciloscopia em 1 dia (de 3,2 para 2,6 dias; p < 0,001). Apesar de diminuir o tempo para inÃcio do tratamento em mÃdia 4 dias com relaÃÃo ao grupo baseline (de 8,2 para 4 dias), essa diferenÃa nÃo foi estatisticamente significante (p = 0,166). ConclusÃes: O escore clÃnico pode ser uma ferramenta Ãtil na detecÃÃo de casos de TB pulmonar. Por sua simplicidade, nÃo necessita de equipamentos caros e complexos para sua execuÃÃo. Ao ser utilizado por um profissional treinado, o questionÃrio poderà gerar informaÃÃes sobre encaminhamentos ou pedidos de exames na abordagem do paciente sintomÃtico respiratÃrio, ou ainda ajudar na decisÃo sobre inÃcio do tratamento.
Objectives: Mainly in regions with the greatest TB burden in the world, there is still a delay for patients to receive the results of the diagnostic exams. Researchers from Rede Brasileira de Tuberculose developed and evaluated the performance of a diagnostic test for pulmonary TB: Neural TB clinical score. The objective of the present work is to evaluate the effectiveness of the Neural TB clinical score in the rapid diagnose of pulmonary tuberculosis in a reference unit. Methods: A pragmatic clinical essay with diagnostic intervention in the second half of the project was conducted. We recruited 351 patients aged 18 years or older, suspected of having pulmonary TB, and we applied the Neural TB clinical score to them. In the first phase of the essay, patients followed the routine of the Hospital. In the second phase, patients had collection of sputum samples for baciloscopy anticipated according to their classification by the score. T-Student test and Mann Whitney test were used to compare two independent subpopulations. Results were considered significant if p value < 0,05. Prevalence ratio and 95% confidence interval were calculated. Kappa index was used to measure conformity between the clinical score and pulmorary TB diagnostic. Results: Neural TB clinical score showed sensitivity of 75,9%, specificity of 48,8% and accuracy of 55% when compared to the diagnostic realised through sputum baciloscopy, sputum culture or clinical-radiological diagnostic altogether. The use of Neural TB clinical score was able to reduce time between patient screening and detection of organisms in a sputum sample slide in 1 day (from 3.2 to 2.6 days; p < 0.001). Although time until beginning the treatment was reduced 4 days in average when compared to the baseline group (from 8.2 to 4 days), this difference was not statistically significant (p = 0.166). Conclusion: The clinical score may be a useful tool for the detection of pulmonary tuberculosis cases. Because it is simple, it does not require expensive or complex equipment for its execution. As it is used by a trained professional, the questionnaire may produce information about referrals or test requests for the respiratory symptomatic patient, or even help in the decision of starting treatment.
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Askeland, Winje Brita. "Comparison of QuantiFERON®TB Gold with tuberculin skin test to improve diagnostics and routine screening for tuberculosis infection among newly arrived asylum seekers to Norway." Thesis, Nordic School of Public Health NHV, 2008. http://urn.kb.se/resolve?urn=urn:nbn:se:norden:org:diva-3182.

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Introduksjon: QuantiFERON®TB Gold (QFT) er en ny blodtest for påvisning av tuberkulosesmitte, men med få data så langt fra undersøkelse av immigranter. Målet med studien var å sammenligne resultat av QFT og tuberkulin hudtest blant nyankomne asylsøkere i Norge og å vurdere hvilken rolle QFT bør ha i screening for latent tuberkulose. Metode: Alle asylsøkere, 18 år eller eldre, som ankom Tanum asylmottak fra september 2005 ble invitert til å delta og ble inkludert etter informert samtykke. Inkludering pågikk inntil et forhåndsbestemt antall på 1000 inkluderte ble nådd. Siste deltager ble inkludert i juni 2006. Deltagelse innebar en QFT test og standardiserte spørsmål, i tillegg til den lovpålagte tuberkulintesten og lungerøntgen. Resultat: Totalt 2813 asylsøkere ankom Tanum asylmottak i inkluderingsperioden (sept 05-juni 06).  Blant de 1000 deltagerne hadde 912 gyldige testresultater og ble inkludert i analysen, 29 % (264) hadde positiv QFT, mens 50 % (460) hadde positiv tuberkulintest (indurasjon > 6mm). Det indikerer en høy andel smittede personer i denne gruppen. Blant deltagere med positiv tuberkulintest hadde 50 % negativ QFT, mens 7 % av dem med negativ tuberkulintest hadde positiv QFT. Det var en signifikant sammenheng mellom økning i tuberkulinutslag og sannsynligheten for å ha positiv QFT. Samsvar mellom testene var 71-79%, avhengig av grenseverdi for tuberkulin. Det var bedre samsvar mellom testene for ikke-vaksinerte personer. Konklusjon: Ved å implementere QFT som rutine kan videre oppfølging avsluttes for 42% av dem som ville ha blitt henvist basert kun på tuberkulinresultat (> 6mm). Andelen som henvises vil være den samme enten QFT implementeres som erstatning for eller som supplement for å bekrefte en positiv tuberkulinreaksjon, men antallet som testes vil variere mye. Ulike tilnærminger vil identifisere samme andel (88-89%) av asylsøkere med positiv QFT og/eller sterkt positiv tuberkulinutslag (>15mm), men ulike grupper vil mistes.
Introduction: QuantiFERON®TB Gold (QFT), a new blood test that detects tuberculosis infection, currently provides few data from immigrant screening. This study aimed to compare results of QFT and tuberculin skin tests (TST) among newly arrived asylum seekers in Norway and also assess the role of QFT in screening for latent tuberculosis. Methods: All asylum seekers, 18 years or older, who arrived at Tanum reception center from September 2005 were invited to participate and included after informed consent. Enrollment was continued until a fixed sample size of 1000 participants was reached. The last participant was included in June 2006. In addition to mandatory TST and chest X-ray, study participants underwent a QFT test and answered standardized questions. Results: A total of 2813 asylum seekers arrived at Tanum reception center during the inclusion period. Among the 1000 study participants, 912 showed valid test results and were included in analysis; 29% (264) had a positive QFT test and 50% (460) tested positive with TST (indurations >6 mm), indicating a high proportion of latent infection within this population. Among the TST-positive participants, 50% were QFT-negative, whereas 7% of the TST-negative participants were QFT-positive. A significant association occurred between increase in size of TST induration and positive QFT result. Test agreement (71%–79%) depended on the chosen TST cut-off and was higher for nonvaccinated individuals. Conclusions: By implementing QFT as a routine screening test further follow up can be avoided for 42% of asylum seekers who would have been referred based only on a positive TST (>6 mm). The proportion of individuals referred remained the same whether QFT replaced TST or confirmed a positive TST; however, the number of individuals tested varied greatly. Different approaches would identify the same proportion (88%-89%) of asylum seekers with either a positive QFT or a strongly positive TST (>15 mm), but different groups will be missed.

ISBN 978-91-85721-53-5

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Gutschmidt, Andrea. "Evaluation of anti-tuberculosis responses in humans using different complementary immunological techniques." Thesis, Stellenbosch : Stellenbosch University, 2013. http://hdl.handle.net/10019.1/79835.

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Thesis (MSc MedSc)--Stellenbosch University, 2013.
ENGLISH ABSTRACT: Background The QuantiFERON In-Tube (QFT IT) assay is an Interferon-gamma release assay (IGRA) which is currently used to detect Mycobacterium tuberculosis (M. tb) infection. It however cannot differentiate between latent infection and active tuberculosis (TB) disease. In an attempt to improve this tool to accurately diagnose active TB, the release of a variety of markers should be assessed in combination with Interferon gamma (IFN- γ). Luminex analysis was previously done on QFT plasma and promising candidates were identified which could be of great value in treatment response studies. IFN-γ ELISpot, are not only used to detect M.tb infection, but is also implicated in vaccine trails to assess immunogenicity. The IFN-γ ELISpot and flow cytometry are the most common assays to assess these phenomena during clinical trials. Our aim therefore was to develop a multi platform immune analysis assay using the QFT IT system. Study design and method The first approach of this study was to optimize the QFT IT assay for flow cytometry applications. The following questions formed part of the optimization study: How does the QFT whole blood assay (QFT-WBA) compare to the currently used WBA? Is antigen re-stimulation required after the initial incubation time and for how long should cells be re-stimulated in the presence of Brefeldin A? The second approach was to use the optimized QFT-WBA for community controls (CTRL), household contacts (HHC) and TB cases, which were recruited from the high TB incidence areas Ravensmead, Uitsig and Elsies River. The infection status of each participant was determined by IFN-γ ELISA and Luminex analysis was performed to measured wide range of cytokine expression. In addition immune cell markers like CD14, CD4, CD8, CD19, and T cell receptor gamma delta (TCRγδ) were characterized; polyfunctional characteristics (IFN-γ, Tumor necrosis factor-alpha (TNF-α) and Interleukin-2 (IL-2)) and proliferation (Ki-67+) of T cells determined by flow cytometry. Results After stimulating the whole blood of the study participants for 22 hours with the M. tb specific antigens, early secreted antigenic target 6 kDa (ESAT-6), culture filtrate protein-10 kDa (CFP-10) and TB7.7 the levels of TNF-α producing CD4 T cells were elevated in TB cases compared to HHCs. After stimulating the whole blood for 6 days TNF-α producing T cells declined in TB cases and HHC showed a higher expression. CD40L+CD4+ (p=0.0225) was increased in HHC while IL-9+CD8+ (0.3230) was decreased in HHC compared to TB cases. Other markers such as IL-5(AG-NIL), IL-13(Ag- NIL), FGF basicAg, GM-CSFNIL, VEGFNIL/(Ag-NIL), MIP-1βAg and MCP-1Ag/(Ag-NIL) showed significant differences between HHC and TB cases. Conclusions The responses in the QFT-based assay were generally comparable to the WBA that is routinely used. The differences of TNF-α expression seen in QFT-WBA and QFTLPA could be explained by the fact that effector T cell responses were measured in the short term assay and the central memory T cell responses in the long term assay. Our study therefore shows that the QFT-based tests can be used to simultaneously assess a wide range of immunological markers and not only IFN-γ expression.
AFRIKAANSE OPSOMMING: Agtergrond Die QuantiFERON In Tube (QFT IT) toets is ‘n Interferon-gamma vrystellingstoets (IGRA) wat huidiglik dien as ‘n maatstaf van Mycobacterium tuberculosis (M. tb) infeksie. Hierdie toets kan egter nie onderskei tussen latente infeksie en aktiewe tuberkulose (TB) nie. ‘n Noemenswaardige verbetering in die vermoë van hierdie toets om aktiewe TB te diagnoseer, berus op die studie van ‘n verskeidenheid vrygestelde merkers, insluitend Interferon gamma (IFN-γ). In vorige Luminex studies op QFT plasma, is belowende kandidate geïdentifiseer wat van groot waarde kan wees vir studies wat fokus op die reaksie tot behandeling. Die IFN-γ ELISpot dien nie net as ‘n maatstaf van M.tb infeksie nie, maar word ook in vaksienproewe betrek om die aard van immuniteit te ondersoek. Die IFN-γ ELISpot toets sowel as vloeisitometriese toetse, is van die mees algemene toetse om hierdie verskynsels te meet, tydens kliniese proewe. Die doel van hierdie studie was dus om die QFT IT sisteem te ontwikkel as ‘n basis vir ‘n multiplatform immunologiese analiseringstoets. Studie ontwerp en metode Die inleidende benadering van hierdie studie was die optimisering van die QFT IT toets, vir vloeisitometrie doeleindes. Die volgende vrae het deel uitgemaak van die optimiseringstudie: Hoe vergelyk die QFT heelbloedtoets (QFT-WBA) met huidige WBAs wat in gebruik is? Word meermalige antigeenstimulasies benodig na die oorspronklike inkubasieperiode en hoe lank moet die tydperk wees vir sellulêre opvolgstimulasie, in die teenwoordigheid van Brefeldin A? As ‘n tweede benadering, was om die geoptimiseerde QFT-WBA te gebruik vir gemeenskapskontroles (CTRL), huishoudelike kontakte (HHC) en TB gevalle. Al drie hierdie groepe was opgeneem uit Ravensmead, Uitsig en Elsies Rivier, areas met betreklik hoë vlakke van TB infeksie. Elke persoon in die studie se vlak van infeksie is vasgestel met behulp van die IFN-γ ELISA en Luminex analiese was uitgevoer, om ‘n wye verskeidenheid uitdrukkingsvlakke van sitokiene te meet. Dies meer, was immuunselmerkers soos CD14, CD4, CD8, CD19 en T sel reseptor gamma delta (TCRγδ) gekarakteriseer. Meervuldige funskionele karakteristieke (IFN-γ, Tumor nekrose faktor-alpha (TNF-α) en Interleukin-2 (IL-2)) en vermenigvuldiging van T-selle, was vasgestel deur middel van vloeisitometrie. Resultate Nadat die heelbloed van studiedeelnemers gestimuleers was met M. tb spesifieke antigene, vroeë afskeidings antigeniese teiken 6kDa (ESAT-6), kultuurfiltraatproteïn 10kDa (CFP-10) en TB7.7, vir 22 uur, was gevind dat vlakke van TNF-α produserende CD4 T selle hoër was in TB pasïente, in vergelyking met HHCs. Nadat die heelbloed vir 6 dae gestimuleer was, het die vlak van TNF-α produserende T-selle afgeneem in TB pasïente, terwyl dit hoër was in HCC. CD40L+CD4+ (p=0.0225) het hoër vlakke bereik in HHC, terwyl IL-9+CD8+ (0.3230) vlakke afgeneem het, in vergelyking met TB pasïente. Ander merkers soos,onder andere, IL-5(AG-NIL), IL-13(Ag-NIL), FGF basicAg, GMCSFNIL, VEGFNIL/(Ag-NIL), MIP-1βAg and MCP-1Ag/(Ag-NIL), het noemenswaardige verskille geopenbaar tussen HHC en TB pasïente.
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28

Rotherham, Lia S. "Isolation and characterization of novel aptamers against the CFP-10/ESAT-6 heterodimer for the development of TB diagnostic tools." Thesis, University of Pretoria, 2012. http://hdl.handle.net/2263/30803.

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Tuberculosis (TB) is one of the biggest killers among infectious diseases, despite the worldwide use of a live attenuated vaccine and several antibiotics. There are an estimated eight million new cases per year and two million deaths annually, which are compounded by the emergence of drug resistance TB and co-infections with HIV. As of 2004, it was estimated that more than 4% of the world’s infected people living with active TB are in South Africa. During this period, South Africa accounted for about 2% of the world’s new TB cases; and approximately 3% of the total deaths due to TB. Despite the enormous burden of TB, conventional approaches to diagnosis used today continue to rely on tests that have major drawbacks. Many of these tests are slow and lack both sensitivity and specificity or require expensive equipment and trained personnel. For example, sputum smear microscopy is insensitive; the culture method is technically complex and slow; chest radiography is non-specific; the tuberculin skin test is imprecise and the results are non-specific; nucleic acid amplification tests and phage display are rapid but specificity and sensitivity are low; and the GeneXpert™ addresses the problems of time and sensitivity but the machine required is extremely expensive. Clearly, TB diagnostics need to be improved and a more specific diagnostic assay should preferably be based on antigens that are present exclusively in Mycobacterium tuberculosis (Mtb) and not in Bacillus Calmette-Guérin (BCG). To help improve TB diagnostics, a systematic evolution of ligands by exponential enrichment (SELEX) process was used to select aptamers that can specifically bind to the CFP-10/ESAT-6 heterodimer, which is an early marker of TB. Anti-CFP-10/ESAT-6 aptamers were screened using an enzyme-linked oligonucleotide assay (ELONA) for binding affinity and specificity. A total of 24 aptamers had significant binding to the CFP-10/ESAT-6 heterodimer. One aptamer, named EA10, which bound to the heterodimer with a dissociation constant (KD) of 8 nM, as determined by surface plasmon resonance (SPR), was used for a proof-of-principle in a TB diagnostic test. Evaluation of 80 clinical sputum samples from TB patients revealed that aptamer EA10 has a specificity of 68% and a sensitivity of 80-100%. These data bode well for the development of the aptamer for accurate diagnosis of TB.
Thesis (PhD)--University of Pretoria, 2012.
Microbiology and Plant Pathology
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29

Schoombie, Johannes Loubser. "Genetic engineering of recombinant anti-mycolic acid antibody fragments for use in tuberculosis diagnostics." Diss., University of Pretoria, 2012. http://hdl.handle.net/2263/23688.

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Mycolic acids are long chain lipids from the cell walls of Mycobacterium tuberculosis. The Nkuku phage display library was previously used to obtain monoclonal antibody binders to mycolic acids. In total 11 binders were obtained of which one was selected (MAC10) for further investigation by genetic engineering as presented in this dissertation. The antibodies of the Nkuku phage display library are in the format of single chain variable fragments (scFv). ScFv’s constitute only the epitope binding domains of an antibody consisting of the VH and VL domains fused into a single chain by a flexible linker protein. The selected anti-mycolic acid scFv is referred to as mycolic acid clone 10 (MAC10). Genes encoding the scFv’s of the Nkuku phage display library were cloned into the plasmid pHEN-1, a phage display vector. This vector is not commercially available or ideally suited for expression of scFv proteins. Therefore two vectors were investigated as possible targets for subcloning. The plasmids pGE20 and pAK400 were previously used for the expression of scFv antibody proteins. Subcloning into plasmid pAK400 proved to be the more efficient of the two investigated for subcloning. This subcloning yielded the recombinant plasmid pAKJS. Following the subcloning scFv protein expression was attempted using the plasmids pMAC10 (derived from pHEN-1) and pAKJS (derived from pAK400). Expression of MAC10 using plasmid pMAC10 in both Escherichia coli TG-1 and HB2151 was constitutive. This demonstrates that plasmid pHEN-1 is a non ideal vector as expression should not occur unless induced. Expression of MAC10 did not occur when pAKJS and Escherichia coli HB2151 were used. This was due to both the vector and expression host producing inhibitor protein for the Lac Z promoter controlling expression of the scFv. The MAC10 gene was subsequently randomized using the directed evolution method, error prone PCR. Sequence analysis of the five selected mutants indicated an average mutation rate of 8.6 mutations per 1000 base pairs. From the combined total of all five mutants, transversions made up the majority of substitutions. The majority of transversion mutations occurred at A-T base pairs. Transition substation mutations that made up the minority of total mutations occurred mostly at G-C base pairs.
Dissertation (MSc)--University of Pretoria, 2012.
Biochemistry
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30

Veerasami, Sowbagium. "A retrospective study of the clinical management and treatment outcomes of patients established on antiretroviral therapy who are newly diagnosed with tuberculosis in the public sector, KwaZulu-Natal." Thesis, Stellenbosch : Stellenbosch University, 2013. http://hdl.handle.net/10019.1/80334.

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Thesis (MCurr)--Stellenbosch University, 2013.
ENGLISH ABSTRACT: Taking into consideration the long duration of standard treatment for Mycobacterium tuberculosis (TB), the high prevalence of HIV co-infection and the growing prevalence of drug-resistant TB, there is an urgent need for improved treatment approaches for TB and HIV. However, there is inadequate information regarding the burden being placed on the Department of Health (DOH) systems by the current treatment of patients established on Antiretroviral Therapy (ART) who are newly diagnosed with TB, and by their clinical management. The aim of the study was to determine what proportion of patients established on ART were newly diagnosed with TB, and what their clinical and treatment outcomes were in different public sector settings in the eThekwini Region, KwaZulu-Natal (KZN). Approval for the study was obtained from the Human Research Committee of Stellenbosch University and from the Biomedical Research Committee, KZN. The study used a retrospective, quantitative, cohort technique at both TB and ART clinics at three sites in the eThekwini region, KZN. These sites were DOH clinics and were selected as they all had a TB clinic and a DOH-registered ART clinic. The study focused on a period of one year prior to a patient established on ART developed TB. The study population comprised all TB patients who attended the selected DOH clinics. A data collection tool was developed and pilot-tested. A small sample of patient files (n=15, representing 2% of the study population) was randomly selected; five from each site. The files and data were excluded from the main study. A total of 1824 files (579 from the TB clinics and 1245 from the ART clinics) were reviewed. The data were captured into an electronic database (EpiData Version 3.3) and analyzed using STATA (Version 11.0) with the assistance of a statistician. The findings show that of the study sample from the TB clinics (N=579), 78% (454/579) were newly diagnosed with TB. Of the new TB cases, 90% (409/454) had pulmonary TB and 71% (413/579) were HIV-positive. Nearly 50% (68/137) of the patients had commenced ART prior to TB diagnosis and treatment, and 14% (19/137) had commenced ART after TB. Of those who commenced ART prior to TB diagnosis and treatment, 29% (20/68) had commenced ART more than three months prior to acquiring TB. The findings from the ART clinics show that of the files (N=1245) reviewed, 40% (501/1245) had TB, and of these 8% (42/501) developed TB after three months or more of ART. Missing data in the patient medical files was a major challenge. The lack of recorded data about ART in the TB clinics and about TB in the ART clinics suggests suboptimal clinical management and poor integration of HIV and TB services. It was therefore not possible to derive a combined HIV-TB outcome measure. Recommendations to promote and implement the integration of TB and HIV services included policy changes and implementation, management and practice suggestions, education and training to integrate TB/HIV services and increase research to identify gaps in clinical management and to improve integration of services.
AFRIKAANSE OPSOMMING: Met inagneming van die lang duur van die standaard behandeling vir Mycobacterium tuberkulose (TB), hoë voorkoms van MIV-infeksie en die groeiende voorkoms van dwelmweerstandige TB, is daar ’n dringende behoefte aan verbeterde behandelingbenaderings vir TB en MIV. Daar is egter ’n gebrek aan inligting oor die las geplaas op die Departement van Gesondheid (DvG) se stelsels deur die huidige behandeling van pasiënte op antiretrovirale terapie (ART) wat gediagnoseer is met TB en deur hul kliniese bestuur. Die doel van die studie was om vas te stel watter persentasie van pasiënte wat op ART gevestig is, wel met TB gediagnoseer is, en wat hul kliniese en behandeling-uitkomste was in verskillende openbare-sektorinstellings in die eThekwini-streek, KwaZulu-Natal (KZN). Goedkeuring vir die studie is verkry van die Menslike Navorsingskomitee van die Universiteit van Stellenbosch en van die Biomediese Navorsingskomitee, KZN. Die studie het gebruik gemaak van ’n retrospektiewe, kwantitatiewe ‘cohort’-tegniek by beide TB en ARB-klinieke op drie plekke in die eThekwini-streek, KZN. Hierdie terreine was DvG-klinieke en is gekies omdat hulle almal oor ’n TB-kliniek en 'n DvGgeregistreerde ART-kliniek beskik. Die studie het gefokus op ’n tydperk van een jaar voor ’n pasiënt wat op ART is, TB ontwikkel het. Die studiepopulasie bestaan uit alle TBpasiënte wat die geselekteerde DvG-klinieke bygewoon het. ’n Data-insamelinginstrument is ontwikkel en getoets. ’n Klein voorbeeld van die pasiëntlêers (n = 15, 2% van die studie bevolking verteenwoordig) is ewekansig gekies: vyf uit elke plek, en die data is vervat in ’n elektroniese databasis (EpiData Version 3,3). ’n Totaal van 1824 lêers (579 in die TB-klinieke en 1245 lêers in die ART-klinieke) is ondersoek. Die data is ontleed deur gebruik te maak van Stata (weergawe 11,0) met die hulp van ’n statistikus. Die bevindinge toon dat van die studiemonster in die TB-klinieke (N = 579), 78% (454/579) met TB gediagnoseer is. Van die nuwe TB-gevalle, het 90% (409/454) pulmonêre TB gehad en was 71% (413/579) MIV-positief. Byna 50% (68/137) van die pasiënte het ART begin vóór hulle TB-diagnose en -behandeling, en 14% (19/137) ART ná TB. Van dié wat ART voor TB-diagnose en -behandeling begin het, het 29% (20/68) meer as drie maande voor die opdoen van TB met ART begin. Die bevindinge van die ART-klinieke toon dat van die lêers (N = 1245) wat bestudeer is, 40% (501/1245) TB het, en hiervan het 8% (42/501) TB na drie of meer maande van ART ontwikkel. Ontbrekende data in die pasiënt se mediese lêers was ’n groot uitdaging. Die gebrek aan aangetekende data oor ART in die TB-klinieke en oor TB in die ART-klinieke dui op suboptimale kliniese bestuur en swak integrasie van MIV- en TB-dienste. Dit was dus nie moontlik om ’n gesamentlike MIV-TB uitkomsmaatreël af te lei nie. Aanbevelings om die integrasie van TB- en MIV-dienste te bevorder en te implementer, het beleidveranderinge en -implementering ingesluit, asook bestuur- en praktykvoorstelle, onderwys en opleiding om TB-/MIV-dienste by DvG-vlak te integreer en meer navorsing om gapings in die kliniese bestuur te identifiseer en die integrasie van dienste te verbeter.
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31

Straub, Marina [Verfasser], and Dirk [Akademischer Betreuer] Wagner. "Interferon-gamma Release Assays zur Diagnostik der latenten Tuberkuloseinfektion bei immunsupprimierten Patienten – Einzelzentrumsauswertung der multizentrischen prospektiven TB-NET-Studie "TIGRA in immunocompromised individuals"." Freiburg : Universität, 2013. http://d-nb.info/112347835X/34.

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32

Bulajic, Bojana. "Clinical presentation and diagnostic work up of suspected pulmonary embolism in a district hospital emergency centre serving a high HIV/TB burden population." Master's thesis, University of Cape Town, 2018. http://hdl.handle.net/11427/29664.

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Introduction: The diagnosis of Pulmonary Embolism (PE) is challenging to make and is often missed in the Emergency Centre. The true incidence of PE in South Africa is unknown. The diagnostic work-up of PE has been improved by the use of Clinical decision rules (CDRs) and CT Pulmonary Angiography (CTPA) in high-income countries. Currently used CDRs have not been validated in the South African environment, where HIV and TB are highly prevalent. Both conditions are known to induce a hyper-coagulable state. Methods: This study was a retrospective chart review of patients with suspected PE that had CTPAs performed from October 2013 to October 2015 at Mitchell’s Plain Hospital in South Africa. Data was collected on demographics, presenting symptoms and signs, vitals, bedside investigations, HIV and TB status, use of CDRs and CTPA result. A Revised Geneva Score was calculated retrospectively and compared to the CTPA result. Results: The median age of patients with confirmed PE was 45 years and 68% were female. The CTPA yield for PE in our study population was 32%. The most common presenting complaint was dyspnoea (83%), followed by cough and chest pain. 29% of patients also had clinical features of DVT. No sign or symptom was seen to be markedly different in those with confirmed PE compared to those without. Among patients with confirmed PE, 37% were HIV positive and 52% had current TB. The retrospective revised Geneva Scores compared poorly with the CTPA results. Discussion: PE remains a diagnostic challenge. Worldwide, the use of CDRs has shown to improve the utilization of CTPA. In our study, the retrospectively calculated CDR was not predictive of PE in a population with a high prevalence of HIV and TB. Emergency physicians should be cautious when making a clinical probability assessment of PE in this setting. However, further studies are needed to determine whether HIV and TB could be independent risk factors for PE.
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33

Louskieter, Lance. "Centering Primary Health Care (PHC) Nurses' experiences in their practice of policy implementation - TB diagnostic policy reform in the Western Cape, South Africa." Master's thesis, University of Cape Town, 2018. http://hdl.handle.net/11427/29488.

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This project focused on the recent global reforms in TB diagnostic policy and the implementation of Xpert MTB/RIF (GeneXpert) diagnostic technology into the health system, as a case to assess the extent to which software issues - particularly the human qualities of the system – mediates policy implementation. It centres the experiences of frontline workers in local implementation contexts as imperative because of frontline workers’ have discretionary power and influence in their practice. The premise of this mini-dissertation is that researchers and policy makers should centre the lived experiences of service delivery level health workers when implementing policy or programmatic reforms. This may deepen people-centred approaches which is essential for health systems strengthening. This mini-dissertation is structured into three parts: Part A: This is the research protocol that was submitted for ethical review and approval to the Faculty of Health Science Ethical Review Committee (FHSERC). The protocol frames the study objectives and the initial intentions of the research study. The justifications for the research question, theoretical framework, the research design, methods for data collection and analysis and timelines are clearly presented and discussed. Part B: Using GeneXpert policy reform implementation as a pathfinder, this section presents an undertaking of a structured narrative review of the existing literature addressing the major barriers and enablers for health systems implementation reform. This review assesses the extent to which people issues and people-centred practices are considered in policy implementation research of GeneXpert. The aim of this section of the dissertation is to identify and map-out literature considering the human experiences and relationships of frontline health workers and how these may intersect with hardware, contextual and social systemic factors, that may potentially mediate the implementation of GeneXpert TB diagnostic policy. Part C: This section presents the background, methodology, findings and interpretations from the research, as a journal-ready manuscript. This paper seeks to contribute to the policy implementation literature in the field of HPSR from the perspective of centering nurses' lived experience – especially nurses who are overburdened and undervalued – as imperative in the field of inquiry. The main findings reflect that nurses are burdened by the pressure to meet policy targets, the encumbrance to enforce administrative and bureaucratic procedure, and the minimal platforms or pathways to input on challenges and innovations back to higher level management and decision makers. Within the context of top-down, target-driven and highly structured and standardized operational processes for diagnosing TB, nurses navigate multiple overlapping and contradictory modes of being in their interactions with patients as a response to these pressures. This paper seeks to offer voice to nurses’ experiences of implementing TB diagnostic policy in PHC settings in SA considering its relationship with broader systemic and contextual influences. It also raises particular issues about tensions between efforts to achieve efficiency and effectiveness through enforcing the system, and facilitating people-centered and responsive practices in implementation.
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34

Gomes, Monica Nunes. "Mycolic acid as antigen or analyte in tuberculosis." Diss., 2007. http://hdl.handle.net/2263/26345.

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Tuberculosis has become one of the world’s most devastating diseases, with more than two million deaths and eight million new cases occurring annually due to the development of drug-resistant strains of Mycobacterium tuberculosis, the breakdown of the immune system of its host by HIV, lapses in public health programmes and the fact that diagnosis of TB is not 100% reliable. Early, affordable, unsophisticated and accurate diagnosis of TB to facilitate timely and proper treatment has become of highest priority to public health. Mycolic acid (MA) is the major lipid cell wall component of Mycobacterium tuberculosis and is unique to mycobacteria and closely aligned genera. Mycolic acids have been shown to be unique antigens for TB diagnosis and have been utilized in standard serodiagnostic techniques, but sensitivity and specificity was found to be unsatisfactory. Two vastly different techniques were investigated in this study – one making use of antibodies and MA, the other, just MA and its unique physical properties of interaction with other MA using fluorescently labelled MA. In the first approach, Sepharose protein-A was employed to trap patient IgG antibodies. The anti-MA antibodies were then quantified by probing with liposomes containing fluorescently labelled MA. Although it generally worked well, a few false –positive and –negative results were obtained. This assay appeared to be more accurate than the standard ELISA immunoassay but it is more labour intensive and not even remotely as amenable to large-scale screening and automation as ELISA. The second approach is based on the release of fluorescent MA from immobilized liposomes on glass by means of the specific attraction that MA in test liposomes or TB patient serum was perceived to have on the immobilized MA. The end-point measured was the remaining fluorescent MA on the surface. Differences were observed between the control and patients’ sera at a very high dilution but not between the HIV negative, TB positive and HIV positive, TB positive patients. This was merely an exploratory investigation and more work still needs to be done before the test is ready for validation with large numbers of serum samples. If subsequent studies confirm these findings, then this concept may be converted into a simple, rapid and affordable TB diagnostic test or be used in combination with the IAsys affinity biosensor to provide a more thorough diagnosis
Dissertation (MSc (Biochemistry))--University of Pretoria, 2009.
Biochemistry
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Naidoo, Romola Suriakumarie. "A retrospective chart review of the prevalence and determinants of deays in the diagnosis of childhood TB." Thesis, 2017. https://hdl.handle.net/10539/25250.

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Submitted in partial fulfillment of the requirements for the degree of Master of Science (Child Health) in the Department of Paediatrics, University of the Witwatersrand, Gauteng, South Africa, 2017
Background: The incidence and morbidity of childhood tuberculosis (TB) in South Africa is high. Objectives: We evaluated the incidence of childhood TB in a regional hospital, the proportion of cases with a delayed diagnosis, and the determinants and outcomes thereof. Method: We conducted a retrospective cross-sectional review of hospital records of paediatric cases that were diagnosed with probable or confirmed TB at Addington Hospital, eThekwini, KwaZulu-Natal (KZN) from July through December 2013. Caregiver delays in diagnosis were based on history taking atinitial presentation, while health care worker or systems delays were calculated fromthe time from first presentation to diagnosis.Healthcare worker and health system delays were classified asbeing of 2-4 weeks and >4 weeksduration. Delays related to health policy implementation were also determined. Results: Fifty nine (74%) of the 80 children who werediagnosed with TBhad their recordsretrieved.The overall childhood TB incidence for Addington Hospital during the study period was 2.5%. Caregiver-related factors impacting on delay in TB diagnosis were observed in 25 (42%) of the 59 cases.Nineteen (32%)childrenhad a delay from initial presentation to TB diagnosis related to healthcare worker and health systems issues.Airway reactivity occurred more frequently in the group ofchildren who had a delay in diagnosis of>4 weeks (8/11, 73%)as compared to the non-delayed group (15/40, 38%), P=0.038. Conclusion: The diagnosis of TB in childrenis delayed in a substantial proportion of children. Significant improvements in healthcare that is provided to these childrenare required to avoid missed opportunities for diagnosis and treatment.
XL2018
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Damte, Tedla Mezemir. "Tuberculosis case detection among HIV positive persons in a hospital in Ethiopia." Diss., 2013. http://hdl.handle.net/10500/13287.

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Collaborative TB/HIV management is essential to prevent and treat TB among HIV-positive TB patients, and to ensure that HIV-positive TB patients are detected and treated appropriately. This quantitative, descriptive, contextual study identified problems encountered during the implementation of TB case detection among HIV-positive individuals in one Ethiopian hospital. During December 2012, 300 checklists were completed about HIV-positive patients’ TB/HIV collaborative management, as reflected in their files. Only 60.2% of HIV-positive patients, who should have received Isoniazid preventive treatment (IPT), were placed on this treatment. X-rays and laboratory examinations of sputum samples were not done according to the Ethiopian guidelines. Most TB patients’ initial screening was done by nurses, not doctors, and included only symptom screening without CD4 count considerations. Managers and healthcare personnel should improve IPT, especially for those with early HIV infection and timely effective treatment for those suffering from TB, before complications arise
Health Studies
Health Studies
M.A. (Public Health)
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Hodkinson, Katherine Elizabeth. "Deep vein thrombosis in the era of high HIV and TB prevalence: a prospective review of its diagnosis and treatment in a quaternary care centre." Thesis, 2017. https://hdl.handle.net/10539/24907.

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A research report submitted to the Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, in partial fulfilment of the requirement for the degree of Master of Medicine (Haematology). Johannesburg, 2017.
Background Venous thromboembolic disease (VTE) is a leading cause of morbidity and mortality worldwide. Human immunodeficiency virus (HIV) and tuberculosis (TB) infections have an aetiological association with VTE. Implementation of national HIV and TB programs in South Africa have changed the burden of these two conditions with resultant effects on VTE prevalence. Furthermore, with the increased use of direct oral anticoagulants (DOACs), baseline thrombosis data is needed in order to evaluate the impact of these new agents. Objectives To determine the real-life baseline VTE characteristics in a pre-DOAC era and to document the association of HIV and TB infections with VTE. Methods This is a single centre prospective cohort study performed in a quaternary care centre at the Charlotte Maxeke Johannesburg Academic Hospital (CMAJH), Gauteng, South Africa. Key inclusion criteria included a signed informed consent by adults (≥ 18 years) with a new episode of thrombosis. Procedures included physical examination, thrombosis risk factor assessment, duplex doppler examination, thrombotic screen tests, inpatient treatment and outpatient followup. Results Ninety-nine participants with confirmed thrombosis met the inclusion criteria. Participants were predominantly black (80%) and female (65%) with a median age of 46 (38-57) years. The HIV and TB prevalence were 53% and 21% respectively. The most common thrombosis risk factors were TB infection (17%) and malignancies (14%). The thrombotic screen assays had a low diagnostic yield. The median time to target international normalized ratio (INR) during hospitalization was 5.5 (4.0-7.0) days and the median duration of hospitalization was 9 (7-11) days. The overall mortality in the cohort at three months post hospitalization was 12%. Conclusion This prospective study provides real-life data of thrombosis diagnosis and management at a quaternary public healthcare facility. This data provides a valuable baseline against which the impact of new DOAC anticoagulants can be assessed.
LG2018
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38

Ngabonziza, J. C. S., Y. M. Habimana, T. Decroo, P. Migambi, A. Dushime, J. B. Mazarati, L. Rigouts, et al. "Reduction of diagnostic and treatment delays reduces rifampicin-resistant tuberculosis mortality in Rwanda." 2019. http://hdl.handle.net/10454/17785.

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Yes
SETTING: In 2005, in response to the increasing prevalence of rifampicin-resistant tuberculosis (RR-TB) and poor treatment outcomes, Rwanda initiated the programmatic management of RR-TB, including expanded access to systematic rifampicin drug susceptibility testing (DST) and standardised treatment.OBJECTIVE: To describe trends in diagnostic and treatment delays and estimate their effect on RR-TB mortality.DESIGN: Retrospective analysis of individual-level data including 748 (85.4%) of 876 patients diagnosed with RR-TB notified to the World Health Organization between 1 July 2005 and 31 December 2016 in Rwanda. Logistic regression was used to estimate the effect of diagnostic and therapeutic delays on RR-TB mortality.RESULTS: Between 2006 and 2016, the median diagnostic delay significantly decreased from 88 days to 1 day, and the therapeutic delay from 76 days to 3 days. Simultaneously, RR-TB mortality significantly decreased from 30.8% in 2006 to 6.9% in 2016. Total delay in starting multidrug-resistant TB (MDR-TB) treatment of more than 100 days was associated with more than two-fold higher odds for dying. When delays were long, empirical RR-TB treatment initiation was associated with a lower mortality.CONCLUSION: The reduction of diagnostic and treatment delays reduced RR-TB mortality. We anticipate that universal testing for RR-TB, short diagnostic and therapeutic delays and effective standardised MDR-TB treatment will further decrease RR-TB mortality in Rwanda.
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39

Afzal, Arsalan. "Tuberculosis screening in a cohort of individuals diagnosed with HIV in Ontario during 2001 to 2009." Thesis, 2012. http://hdl.handle.net/10155/226.

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Tuberculosis (TB) is a preventable and a treatable disease yet it is considered to be one of the most common infections seen in HIV. People who are infected with HIV are 20 times more likely to develop TB than those without HIV. Globally, there are nearly 40 million people living with HIV and at least one-third of them are infected with TB. Ontario accounts for the highest number of TB cases in Canada yet HIV-TB co-infection in Ontario is not well described. Despite the close relationship between TB and HIV and increasing efforts to fight both concurrently, TB continues to create economic and social burden in HIV infections. Our study estimates the prevalence of active and latent TB and identifies risk factors associated with TB in a cohort of individuals living with HIV in Ontario. Cases diagnosed with HIV during 2001 to 2009 were extracted from the Ontario HIV Treatment Network Cohort Study (OCS). Reviewing Mantoux test results, diagnoses and medication history, identified active and latent TB cases. Period prevalence was estimated by proportion with TB and multivariate analyses were performed to identify associated factors. One thousand two hundred and ninety-three cases (1293) met our selection criteria. Three hundred and eighty four (384; 29.7%) were 29 years or younger, 805 (62.3%) aged between 30 years and 50 years and 104 (8.0%) aged 50 years or older. One thousand and nine (1009; 78.0%) were males. Four hundred and sixty six (466; 36.0%) had at least one record of a Mantoux skin test. The prevalence of active TB was 76/1293 = 0.0587 or 5.87% (95% CI 4.6% to 7.0%) whereas the prevalence of latent TB varied from 5.26% (68/1293 = 0.0526) 95% (CI 4.0% - 6.5%) to 11.37% (53/466 = 0.1137) 95% CI (8.2% to 13.7%) depending on the methodology. In the multivariate analysis, factors associated with active TB were age and birthplace. Individuals 50 years and older were more likely to have active TB than individuals 30 years and younger (OR 4.3 CI (1.7-12.7), p <0.01). Individuals born in Africa were more likely to have active TB than Canadian born (OR 14; 95% CI (5.9 – 32.8) p < 0.001). Factors associated with latent TB were sex and birthplace. Females were more likely to have latent TB than males (OR 2.4; 95% CI (1.1 – 5.2) p < 0.05). Individuals born in Africa were more likely to have latent TB than Canadian born (OR 12.3; 95% CI (4.7 – 32.1) p < 0.001). TB remains a major problem in persons infected with HIV with rates disproportionally high among the foreign born population. Low rates of Mantoux tests in OCS present a missed opportunity for active TB prevention among individuals with HIV. To identify individuals with higher risk of having TB after HIV diagnosis, better screening tools to identify latent TB are needed. Consideration should be given to data capture systems that would ideally be linked between Public Health and HIV clinics.
UOIT
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40

Balogun, Mohammed Olusegun. "Stereocontrolled synthesis of a thiolated mycolic acid for development of novel TB diagnostics." Thesis, 2012. http://hdl.handle.net/2263/30875.

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The current global tuberculosis epidemic has shown the need to urgently replace the aged anti-TB armamentarium. The search for a fast, accurate and reliable diagnosis of active TB has emerged as the spearhead in efforts to defeat the scourge. Traditional diagnostics that have existed for more than a century are at best inadequate against the wilier modern forms of the disease like TB-HIV/AIDS co-infection and the drug resistant TB. The development of mycolic acid based serodiagnostics has introduced a powerful tool that gives high hopes of solving the diagnostic challenges of a large percentage of TB cases. To date, these biosensor-based technologies require the immobilization of MA antigens on a gold substrate for antibody recognition. Several challenges need to be resolved before these new technologies can be rolled out as affordable and reliable diagnostic tools. This project sets out primarily to economize the synthesis of MA and develop a new and stable antigenic surface that will improve reliability of tests. Chemical knowledge of MA has been growing over the past century but total organic synthesis of the various forms of these complex molecules have only been achieved in the past decade. This project focused on improving a recently developed synthetic route to the mycolic motif. It successfully scaled up the synthesis by systematically troubleshooting various aspects of the synthetic protocol. This resulted in the reduction of the number of reactions by at least 6 steps compared to the current literature method [Scheme I]. Importantly, this method has the potential of being extended to the synthesis of much longer fragments of the mycolic acid molecule.
Thesis (PhD)--University of Pretoria, 2012.
Chemistry
PhD
Unrestricted
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41

Salindri, Argita. "Diabetes Reduces the Rate of Sputum Culture Conversion in Patients with Newly Diagnosed Multidrug Resistant Tuberculosis." 2015. http://scholarworks.gsu.edu/iph_theses/421.

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Background: Risk factors for acquired multidrug resistant tuberculosis (MDR TB) are well described but risk factors of primary MDR TB is understudied. We aimed to 1) assess risk factors for primary MDR TB, including diabetes, and 2) determine if diabetes reduced the rate of sputum culture conversion in patients with primary MDR TB. Methods: From 2011-2014 we conducted a prospective cohort study at the National Center for TB and Lung Disease in Tbilisi, Georgia. Adult (≥35 years) patients with primary TB were eligible. MDR TB was defined as resistance to at least rifampicin and isoniazid. Patients with HbA1c ≥6.5% were defined to have diabetes. Polytomous regression was used to estimate the association of patient characteristics with drug resistance. Cox regression was used to compare the hazard rate of sputum culture conversion in patients with and without diabetes. Results: Among 318 patients, 268 had drug susceptibility test results. Among patients with DST results, 19.4% was primary MDR TB and 13.4% had diabetes. In adjusted analyses, diabetes (aOR 2.51 95%CI 1.00 – 6.31) and lower socioeconomic status (aOR 3.51 95%CI 1.56 – 8.20) were associated with primary MDR TB. Among patients with primary MDR TB, 44 (84.6%) converted sputum cultures to negative. The hazard rate of sputum culture conversion was lower among patients with diabetes (aHR 0.34 95%CI 0.13 – 0.87) and among smokers (aHR 0.16 95%CI 0.04 – 0.61). Conclusions: We found diabetes to be associated with an increased risk of primary MDR TB; both diabetes and smoking were associated with a decreased rate of sputum culture conversion.
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42

Saul, Dominik. "Diagnostik der Tuberkulose - Bedeutung des γ-Interferon-Tests." Doctoral thesis, 2014. http://hdl.handle.net/11858/00-1735-0000-0022-5E48-F.

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Trotz der weltweit 14 Millionen Erkrankten ist die Diagnostik der Tuberkulose schwierig und langwierig - eine Therapie beeinträchtigt die Patienten unter Umständen über einen langen Zeitraum. Interferon-γ-Release-Assays (IGRAs) sollten bei ihrer Einführung im Jahr 2005 diagnostische Unsicherheiten ausräumen helfen, jedoch blieb der genaue diagnostische Wert des Tests, vor allem in Kliniken mit einer hohen Prä-Test-Wahrscheinlichkeit, unklar. Die Wertigkeit dieses Testverfahrens in der Lungenfachklinik Immenhausen zu untersuchen war daher Aufgabe der vorliegenden Arbeit. Dazu wurden von 2009 bis 2012 in dieser Klinik 112 Krankheitsfälle mit Tuberkulose retrospektiv untersucht und ausgewertet. Dabei ergab sich für den QuantiFERON®-TB Gold-Test ein positiv prädiktiver Wert von 84,8% und eine Sensitivität von 88,9%, wenn man als Referenz alle zugelassenen Nachweisverfahren heranzog. Die Sensitivität des QuantiFERON®-TB Gold war signifikant höher als die des Tuberkulin-Hauttests (p=0,0008) und der Sputum-Anreicherung (p<0,0001), während sich Kultur und QuantiFERON®-TB Gold -Test nicht signifikant unterschieden (p=0,1435). Das Ergebnis des Tuberkulin-Hauttests (in mm) und die prozentuale Auswertung des QuantiFERON®-TB Gold-Tests ließen sich in eine Korrelation bringen (p=0,0828), allerdings wären für eine Einordnung dieses Zusammenhangs mehr Falldaten vonnöten. Die Analyse der falsch-negativen Quantiferon-Tests lieferte individuelle Erklärungsmöglichkeiten, jedoch keine regelhafte Ursache. Diese Ergebnisse lassen den Schluss zu, dass es sich beim QuantiFERON®-TB Gold-Test um eine gute, der Anreicherung und dem Tuberkulin-Hauttest überlegene, jedoch nicht den Goldstandard „Kultur“ verdrängende Methode zum Nachweis einer Tuberkulose handelt.
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43

Ng, K. C. S., J. C. S. Ngabonziza, P. Lempens, Jong B. C. de, Leth F. van, and Conor J. Meehan. "Bridging the TB data gap: in silico extraction of rifampicin-resistant tuberculosis diagnostic test results from whole genome sequence data." 2019. http://hdl.handle.net/10454/17491.

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Yes
Background: Mycobacterium tuberculosis rapid diagnostic tests (RDTs) are widely employed in routine laboratories and national surveys for detection of rifampicinresistant (RR)-TB. However, as next-generation sequencing technologies have become more commonplace in research and surveillance programs, RDTs are being increasingly complemented by whole genome sequencing (WGS). While comparison between RDTs is difficult, all RDT results can be derived from WGS data. This can facilitate continuous analysis of RR-TB burden regardless of the data generation technology employed. By converting WGS to RDT results, we enable comparison of data with different formats and sources particularly for low- and middle-income high TB-burden countries that employ different diagnostic algorithms for drug resistance surveys. This allows national TB control programs (NTPs) and epidemiologists to utilize all available data in the setting for improved RR-TB surveillance. Methods: We developed the Python-based MycTB Genome to Test (MTBGT) tool that transforms WGS-derived data into laboratory-validated results of the primary RDTs—Xpert MTB/RIF, XpertMTB/RIF Ultra, GenoType MDRTBplus v2.0, and GenoscholarNTM+MDRTB II. The tool was validated through RDT results of RR-TB strains with diverse resistance patterns and geographic origins and applied on routine-derived WGS data. Results: The MTBGT tool correctly transformed the single nucleotide polymorphism (SNP) data into the RDT results and generated tabulated frequencies of the RDT probes as well as rifampicin-susceptible cases. The tool supplemented the RDT probe reactions output with the RR-conferring mutation based on identified SNPs. The MTBGT tool facilitated continuous analysis of RR-TB and Xpert probe reactions from different platforms and collection periods in Rwanda. Conclusion: Overall, the MTBGT tool allows low- and middle-income countries to make sense of the increasingly generated WGS in light of the readily available RDT.
Erasmus Mundus Joint Doctorate Fellowship grant 2016- 1346.
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44

Drayton, Dexter Marlon. "Characterizing tuberculosis among persons from countries with varying levels of TB-HIV endemicity who were diagnosed in Ontario during 1997--1998." 2005. http://link.library.utoronto.ca/eir/EIRdetail.cfm?Resources__ID=362455&T=F.

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45

Kim, Nari. "A Novel Approach for Detection of Several Tuberculosis Markers Using Diffractive Optics." Thesis, 2011. http://hdl.handle.net/1807/27345.

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Tuberculosis (TB) is an important disease worldwide. Currently, one-third of the world’s population is infected with TB, and it is a leading cause of death among people living with HIV. Immediate but also accurate diagnosis is required for disease control, yet available diagnostics cannot do both simultaneously. Therefore, designing a technique that can diagnose the disease correctly in the shortest possible time is in great demand in order to stop its spread. Diffraction-based sensing is a novel technique for measuring of biomolecular interaction that has potential for disease diagnosis. In this study, diffraction-based sensing successfully demonstrated its usefulness for diagnostics of TB using recombinant TB antigen, or by detection of interferon-γ that is produced from white blood cells when the immune system activates. The feasibility of the technology was also evaluated in terms of providing real time observation, reducing diagnostic duration, and increasing sensitivity of detection.
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