Browsing by Subject "Tuberculosis"

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  • Kuosmanen, Soile (Helsingfors universitet, 2013)
    The lower respiratory infection tuberculosis (TB) has been the leading cause of death for centuries causing millions of deaths worldwide. The development of antibiotic therapy has reduced the morbidity and mortality during the 20th century, at least in the developed countries. However, tuberculosis is still the world's second leading cause of death from infectious diseases. Although TB can be treated and even cured with drug therapy, the treatment is extremely long and requires 6-9 months constant drug therapy. This prolonged treatment causes poor patient compliance, which is usually the reason for the selection of drug resistant and often multidrug (MDR-TB) or even extensively drug-resistant (XDR-TB) TB bacteria. Limitations of available therapies and the emergence of drug-resistant strains have intensified the search for new drugs from natural sources. Marine micro- and macro-organisms have proven to be an excellent source of structurally unique biologically active natural products. EU FP7 -funded MAREX project, launched in 2010, aims at identifying new biologically active compounds from marine sources. This Master's thesis was carried out as a part of the MAREX project. The aim of this study was to optimize and validate a reproducible method to determine antimicrobial activity of natural products against Mycobacterium smegmatis, which is a widely used non-pathogenic surrogate model for TB. In the present study, spectrophotometric microplate assay was optimized and validated using existing antibacterial agents ciprofloxacin and rifampicin as reference compounds. The assay was performed on 96-well plate by using two detection techniques, absorbance measurement and a colorimetric indicator, for the antibacterial MIC end-point determination. The results obtained by the described methods were compared with each other in order to achieve the most optimal assay conditions. The quality control parameters S/B, S/N and Z' factor were used in order to determine the optimal experimental conditions for the assay. Obtaining reliable results with the turbidimetric method required incubation for two days in the case of ciprofloxacin, and for five days with rifampicin. Colorimetric measurement led to similar results as the turbidimetric measurement for both of the reference compounds. The method was further used for the screening of a group of marine extracts. None of the 21 samples tested showed significant activity against M. smegmatis.
  • Holmberg, Ville; Soini, Hanna; Kivelä, Pia; Ollgren, Jukka; Ristola, Matti (2019)
    Background: Tuberculosis (TB) is a major cause of death in HIV patients worldwide. Here we describe the epidemiology and outcome of HIV-TB co-infections in a high-income country with low TB incidence and integrated HIV and TB therapy according to European guidelines. Methods: This study was based on the HIV cohort of the Helsinki University Hospital which includes all HIV patients in the Helsinki region with a population of 1.5 million. Totally, 1939 HIV-positives who have been under follow-up between 1998 and 2015 were included. Results: TB was diagnosed in 53 (2.7%) of the HIV-patients. The TB incidence rate was higher in injecting drug users (IRR 3.15; 95% CI 1.33-7.52) and heterosexuals (IRR 3.46; 95% CI 1.64-7.29) compared to men having sex with men. The incidence rate was also higher in those born in Sub-Saharan Africa (IRR 3.53; 95% CI 1.78-7.03) compared to those born in Finland. There was a significant reduction in the total TB incidence rate of 59% per 6-year period between 1998 and 2015 (p <0.001). In injecting drug users there was a reduction in incidence rate from 1182 to 88 per 100,000 (p <0.001) and in people born in Sub-Saharan Africa from 2017 to 195 per 100,000 (p <0.001). Among the 53 HIV-TB co-infected cases, one female and 15 males died during follow up. HIV was the primary cause of death in five patients but none of the deaths were caused by TB. Conclusion: The incidence rate of tuberculosis among HIV-positives in Finland has been declining between 1998 and 2015. Among injecting drug users, the reduction is probably explained by harm reduction interventions and care in comprehensive care centers in Helsinki. The increased coverage of antiretroviral therapy is probably another main reason for the decline in TB incidence rates. Despite good treatment results for both HIV and TB, the all-cause mortality among Finnish males with HIV-TB was high, and common causes of death were intoxications and suicides.
  • Holmberg, Ville; Soini, Hanna; Kivelä, Pia; Ollgren, Jukka; Ristola, Matti (BioMed Central, 2019)
    Abstract Background Tuberculosis (TB) is a major cause of death in HIV patients worldwide. Here we describe the epidemiology and outcome of HIV-TB co-infections in a high-income country with low TB incidence and integrated HIV and TB therapy according to European guidelines. Methods This study was based on the HIV cohort of the Helsinki University Hospital which includes all HIV patients in the Helsinki region with a population of 1.5 million. Totally, 1939 HIV-positives who have been under follow-up between 1998 and 2015 were included. Results TB was diagnosed in 53 (2.7%) of the HIV-patients. The TB incidence rate was higher in injecting drug users (IRR 3.15; 95% CI 1.33–7.52) and heterosexuals (IRR 3.46; 95% CI 1.64–7.29) compared to men having sex with men. The incidence rate was also higher in those born in Sub-Saharan Africa (IRR 3.53; 95% CI 1.78–7.03) compared to those born in Finland. There was a significant reduction in the total TB incidence rate of 59% per 6-year period between 1998 and 2015 (p < 0.001). In injecting drug users there was a reduction in incidence rate from 1182 to 88 per 100,000 (p < 0.001) and in people born in Sub-Saharan Africa from 2017 to 195 per 100,000 (p < 0.001). Among the 53 HIV-TB co-infected cases, one female and 15 males died during follow up. HIV was the primary cause of death in five patients but none of the deaths were caused by TB. Conclusion The incidence rate of tuberculosis among HIV-positives in Finland has been declining between 1998 and 2015. Among injecting drug users, the reduction is probably explained by harm reduction interventions and care in comprehensive care centers in Helsinki. The increased coverage of antiretroviral therapy is probably another main reason for the decline in TB incidence rates. Despite good treatment results for both HIV and TB, the all-cause mortality among Finnish males with HIV-TB was high, and common causes of death were intoxications and suicides.
  • Erhola, Marina; Vasankari, Tuula; Jormanainen, Vesa; Toppila-Salmi, Sanna; Herrala, Jaakko; Haahtela, Tari (2019)
  • Sillanpää, Alina (Helsingin yliopisto, 2021)
    Tuberculosis (TB) still ranks as one of the most dangerous infectious diseases around the world and it is accountable for over 1.5 million deaths every year. World Health Organization has estimated that one fourth of the world’s population is infected with Mycobacterium tuberculosis. The current treatment against TB has drawbacks and the only available vaccine against TB does not provide sufficient protection against the disease and therefore new treatments are much needed. There has also been a lack of good animal models, but the zebrafish (Danio rerio) have been recently found to be a good model to study especially granuloma formation, latency, and reactivation of TB. Their natural pathogen, Mycobacterium marinum causes similar infection in the fish than M. tuberculosis in humans. One characteristic of TB is the formation of granulomas, which are aggregates of immune cells that contain the bacteria. However, M. tuberculosis can escape the granuloma and in such a way spread in the host. The inflammasome is an innate immune system mechanism that activates the immunological response in an infection and has a role in the formation of granulomas. PYCARD is an adaptor protein that has a role in inflammasome activation, which makes it an interesting target when studying the immunological response against M. tuberculosis infection. In this study, granuloma formation in pycard-/- and pycard+/+ zebrafish were compared. The granulomas were studied for their size, location, structure and hypoxicity, and the number of granulomas in each fish was counted. Also, the number of free bacteria was assessed. No significant differences were found in any of these aspects between pycard-/- and pycard+/+ fish. Variation between individual fish was great in both groups.
  • Salih, Enass Y. A.; Julkunen-Tiitto, Riitta; Luukkanen, Olavi; Fahmi, Mustafa K. M.; Fyhrquist, Pia (2021)
    In Sudanese traditional medicine, decoctions, macerations, and tonics of the stem and root of Combretum hart-mannianum are used for the treatment of persistent cough, a symptom that could be related to tuberculosis (TB). To verify these traditional uses, extracts from the stem wood, stem bark, and roots of C. hartmannianum were screened for their growth inhibitory effects against Mycobacterium smegmatis ATCC 14468. Methanol Soxhlet and ethyl acetate extracts of the root gave the strongest effects (MIC 312.5 and 625 mu g/ml, respectively). HPLC-UV/DAD and UHPLC/QTOF-MS analysis of the ethyl acetate extract of the root led to the detection of 54 compounds, of which most were polyphenols and many characterized for the first time in C. hartmannianum. Among the major compounds were terflavin B and its two isomers, castalagin, corilagin, tellimagrandin I and its derivative, (S)-flavogallonic acid dilactone, punicalagin, and methyl-ellagic acid xylopyranoside. In addition, di-, tri- and tetragalloyl glucose, combregenin, terminolic acid, cordifoliside D, luteolin, and quercetin-3-O-galactoside-7-O-rhamnoside-(2 -> 1)-O-beta-D-arabinopyranoside were characterized. Luteolin gave better growth inhibition against M. smegmatis (MIC 250 mu g/ml) than corilagin, ellagic acid, and gallic acid (MIC 500-1000 mu g/ml). Our study justifies the use of C. hartmannianum in Sudanese folk medicine against prolonged cough that could be related to TB infection. This study demonstrates that C. hartmannianum should be explored further for new anti-TB drug scaffolds and antibiotic adjuvants.
  • Varimo, Tero; Teivaanmäki, Tiina; Nieminen, Tea; Metsäranta, Marjo (2020)
  • Myntti, Tarja; Saisto, Terhi; Wartiovaara-Kautto, Ulla (2018)
  • Grierson, Sirkku; Kivelä, Pia; Soini, Hanna; Räsänen, Sirpa; Miettinen, Katri; Marttila, Jane; Vauhkonen, Mikko; Vasankari, Tuula (2017)
    Maahanmuuttajien, jotka eivät ole turvapaikanhakijoita tai pakolaisia, keuhkotuberkuloosiseulonta toteutuu vain osassa kunnista ja niissäkin vaihtelevasti. Ongelmia on ollut mm. seulottavien tavoittamisessa.
  • Anttila, Veli-Jukka; Niku, Suvi; Janes, Rita (2020)
    Syövän ilmaantuvuuden suurentuessa syöpähoidot lisääntyvät. Sekä itse syöpä että sen hoito altistavat infektioille, joiden ehkäiseminen ja hoito ovat olennainen osa syöpäpotilaan hoitoa. Tavanomaisiin solunsalpaajahoitoihin liittyvä neutropenia ja limakalvojen vaurioituminen altistavat bakteeri-infektioille, joiden hoito poikkeaa immuunivasteeltaan normaalin henkilön infektioiden hoidosta. Myös eri syöpäpotilaiden välillä esiintyy vaihtelua infektioiden yleisyyden, luonteen ja vaikeuden osalta. Neutropeeniset kuumeilevat potilaat voidaan jakaa pienen ja suuren infektioriskin ryhmiin, joiden empiirinen mikrobilääkehoito poikkeaa toisistaan. Lymfopenia puolestaan altistaa virus- ja opportunisti-infektioille, joista osa on ehkäistävissä lääkityksin. Kohdennetut, uusilla mekanismeilla vaikuttavat syöpälääkkeet aiheuttavat vähemmän neutropeenisiä infektioita, mutta niihin liittyvät omat infektiohaasteensa.
  • Kontturi, Antti; Santiago, Begona; Tebruegge, Marc; von Both, Ulrich; Salo, Eeva; Ritz, Nicole (2016)
    Background: Recent reports indicate an ongoing BCG shortage that may influence immunisation practice. This study aimed to determine current availability of BCG vaccine across Europe, and implications on immunisation practices and policies in Europe. Methods: Web-based survey among Paediatric Tuberculosis Network European Trials Group (ptbnet) members, between May and October 2015. Results: Twenty individuals from 13 European countries participated. Ongoing shortages were reported in eight countries routinely using BCG (8/11, 73%). As a consequence of the shortage, BCG was not given as completely unavailable in some countries (2/8, 25%), was given only whenever available (1/8,13%), or only in certain regions of the country (1/8, 13%). Strategies reported to reduce loss of immunisation were administration to selected high-risk individuals (2/8, 25%), or cohorting vaccinees on specific days to maximise the use of multi-dose vials (3/8, 38%). Authorities in two countries each were considering a change of manufacturer/supplier (2/8, 25%). Conclusions: The BCG shortage in Europe leads to significant changes in immunisation policies including changes of BCG vaccine strain and manufacturer. In addition, infants and children eligible for immunisation are at risk of not receiving BCG. To ensure necessary BCG immunisations, collaboration between national health agencies and vaccine manufacturers is crucial. (C) 2016 Elsevier Ltd. All rights reserved.
  • Rajalahti, Iiris; Ruutu, Petri; Virtanen, Mikko; Salo, Eeva; Järvinen, Asko; Vasankari, Tuula; Soini, Hanna (2017)
    Suomessa todetaan alle 300 uutta tuberkuloositapausta vuodessa. Ilmaantuvuus on samalla tasolla kuin muissa Pohjoismaissa. Epidemiologinen tilanne on muuttumassa. Sairastuneiden keski-ikä laskee, koska nuorten maahanmuuttajien osuus kasvaa. Haasteita ovat sairastuneiden varhainen löytäminen, lääkehoidon toteutus, kustannustehokas riskiryhmien seulonta ja tartunnanjäljitys, rekisterijärjestelmän laajentaminen ja työntekijöiden säännöllisestä koulutuksesta huolehtiminen. Tärkeimmät muutokset uudessa tartuntatautilaissa ovat eräissä työtehtävissä toimivien uudistetut ¬tuberkuloosin seulontakriteerit sekä mahdollisuus rekisteröidä altistuneita.