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Molekylær epidemiologi blant pasienter med multiresistent tuberkulose i Tigray, Etiopia
Get PDFTuberculosis (TB), which is caused by closely related Mycobacterium tuberculosis complex (MTBC) species, is an ancient human disease that gravely affects millions of people every year. TB is a preventable and treatable infectious disease. The continuing emergence and spread of multidrug-resistant tuberculosis (MDR-TB ) threaten the global TB control efforts. TB is the first killer among infectious diseases worldwide. According to the WHO report, there were an estimated 10.0 million incident cases, 1.4 million TB deaths, with more than 95% of these deaths in developing countries in 2019. Ethiopia is among the three high TB, TB/HIV, and MDR-TB burden countries. In 2019 in Ethiopia, there were 157,000 new TB cases, 1,400 MDR/RR-TB cases and 23,800 death from TB. This thesis aimed to describe the molecular epidemiology of multidrugresistant Mycobacterium tuberculosis among pulmonary TB patients in Tigray Region, Ethiopia.
Three hundred sputum samples were collected from six hospitals of the Tigray Region between July 2018 and August 2019. The 227 samples culture positive for MTBC were subjected to drug susceptibility test to 1st- and 2nd- line anti-TB drugs using line probe assay. Among the 227 positive cultures, 74 samples were sequenced using whole-genome sequencing (WGS).
WGS analysis showed diversified Mycobacterium tuberculosis genotypes circulating in the region, with L4 as the predominant genotype. The overall proportion of MDR-TB was high. The high proportion of MDR-TB among new and previously treated patients is alarming and calls for an urgent intervention to improve patient management. The high proportion of MDR-TB among newly diagnosed cases and the high level of recent transmission index indicates an ongoing transmission, which suggests the need for an enhanced TB control program performance to interrupt transmission. The study highlighted the usefulness of mutations at rpoB, katG, embB, rpsL, pncA, ethA, gyrA and rrs genes as a molecular marker for the rapid detection of resistance to RIF, INH, ETB, SM, PZA, ETH, FLQs and injectable 2nd-line anti-TB drugs, respectively. Besides the canonical mutations, a significant number of disputed rpoB mutations were also reported.
Overall, the regional TB control program should be strengthened to detect and provide appropriate early treatment and follow-up for drug-resistant TB (DR-TB) cases. Abiding by the five WHOrecommended priority actions for DR-TB management is necessary to reduce the current high MDR-TB burden in the study region. Periodic surveillance of drug-resistance conferring mutations, early diagnosis and treatment of TB, and scaling up of drug susceptibility testing facilities to prevent and control the transmission of DR-TB in the community is recommended.Tuberkulose (TB) forårsakes av nært beslektede arter innen Mycobacterium tuberculosiskomplekset (MTBC), og er en eldgammel, alvorlig sykdom hos mennesker som rammer millioner hvert år. TB er en smittsom sykdom som kan forebygges og behandles, men fremveksten og spredningen av multiresistent tuberkulose (MDR-TB) truer den globale bekjempelsesinnsatsen. TB er den smittsomme sykdommen som gir størst antall dødsfall i verden. WHO anslår at det i 2019 var anslagsvis 10,0 millioner tilfeller, 1,4 millioner TB dødsfall, med mer enn 95% av disse dødsfallene i utviklingsland. Etiopia er blant de tre land som er mest belastet, med høye tall av TB, TB / HIV og MDR-TB. I Etiopia var det i 2019 157.000 nye TB-tilfeller, 1400 MDR tilfeller og 23 800 dødsfall fra TB. Denne doktorgradens overordnede mål var å beskrive den molekylære epidemiologien til sjukdom forårsaket av multiresistent Mycobacterium tuberculosis blant lungepasienter i Tigray-regionen, Etiopia.
Tre hundre sputumprøver ble samlet inn fra seks sykehus i Tigray-regionen mellom juli 2018 og august 2019. Av disse ble de 227 prøvene som var positive for MTBC, undersøkt med en følsomhetstest mot 1. og 2. linje anti-TB medisiner ved bruk av Line Probe Assay. Av de 227 positive kulturene ble 74 prøver sekvensert ved bruk av helgenomsekvensering (WGS).
WGS-analysene viste at forskjellige MTBC-genotyper som sirkulerte i regionen, med L4 som den dominerende genotypen. Den høye andelen MDR-TB blant nye og tidligere behandlede pasienter er alarmerende og stiller store krav til en forbedret pasienthåndtering. Den høye andelen MDR-TB blant nylig diagnostiserte tilfeller og det høye nivået av nylig overførte infeksjoner indikerer en pågående overføring, og antyder behovet for en forbedret ytelse av TB-kontrollprogrammet for å avbryte overføringen. Studien fremhevet nytten av mutasjoner ved rpoB, katG, embB, rpsL, pncA, ethA, gyrA og rrs gener som en molekylær markør for rask påvisning av resistens mot RIF, INH, ETB, SM, PZA, ETH, FLQ og injiserbare andrelinje anti-TB medisiner.
Samlet sett bør det regionale TB-kontrollprogrammet styrkes for å oppdage og gi tilpasset passende behandling og oppfølging av TB-tilfeller. Å identifisere TB-kontrollprogrammets begrensninger i regionen, og følge de fem WHO-anbefalte prioriterte tiltakene for styring av DRTB, er nødvendig for å redusere den nåværende høye MDR-TB-belastningen i studieområdet. Det anbefales periodisk overvåking av mutasjoner som gir antibiotikaresistens, tidlig diagnose og behandling av TB, og oppskalering av fasiliteter for testing av isolater for antibiotikafølsomhet for å forhindre og kontrollere overføring av DR-TB i samfunnet.Mekelle Universit
Molecular epidemiology of multidrug-resistant tuberculosis among pulmonary tuberculosis patients in Tigray Region, Ethiopia
No full textTuberculosis (TB), which is caused by closely related Mycobacterium tuberculosis complex (MTBC) species, is an ancient human disease that gravely affects millions of people every year. TB is a preventable and treatable infectious disease. The continuing emergence and spread of multidrug-resistant tuberculosis (MDR-TB ) threaten the global TB control efforts. TB is the first killer among infectious diseases worldwide. According to the WHO report, there were an estimated 10.0 million incident cases, 1.4 million TB deaths, with more than 95% of these deaths in developing countries in 2019. Ethiopia is among the three high TB, TB/HIV, and MDR-TB burden countries. In 2019 in Ethiopia, there were 157,000 new TB cases, 1,400 MDR/RR-TB cases and 23,800 death from TB. This thesis aimed to describe the molecular epidemiology of multidrugresistant Mycobacterium tuberculosis among pulmonary TB patients in Tigray Region, Ethiopia.
Three hundred sputum samples were collected from six hospitals of the Tigray Region between July 2018 and August 2019. The 227 samples culture positive for MTBC were subjected to drug susceptibility test to 1st- and 2nd- line anti-TB drugs using line probe assay. Among the 227 positive cultures, 74 samples were sequenced using whole-genome sequencing (WGS).
WGS analysis showed diversified Mycobacterium tuberculosis genotypes circulating in the region, with L4 as the predominant genotype. The overall proportion of MDR-TB was high. The high proportion of MDR-TB among new and previously treated patients is alarming and calls for an urgent intervention to improve patient management. The high proportion of MDR-TB among newly diagnosed cases and the high level of recent transmission index indicates an ongoing transmission, which suggests the need for an enhanced TB control program performance to interrupt transmission. The study highlighted the usefulness of mutations at rpoB, katG, embB, rpsL, pncA, ethA, gyrA and rrs genes as a molecular marker for the rapid detection of resistance to RIF, INH, ETB, SM, PZA, ETH, FLQs and injectable 2nd-line anti-TB drugs, respectively. Besides the canonical mutations, a significant number of disputed rpoB mutations were also reported.
Overall, the regional TB control program should be strengthened to detect and provide appropriate early treatment and follow-up for drug-resistant TB (DR-TB) cases. Abiding by the five WHOrecommended priority actions for DR-TB management is necessary to reduce the current high MDR-TB burden in the study region. Periodic surveillance of drug-resistance conferring mutations, early diagnosis and treatment of TB, and scaling up of drug susceptibility testing facilities to prevent and control the transmission of DR-TB in the community is recommended
Diagnostic Delay among New Smear Positive Pulmonary Tuberculosis Patients in Amhara Region, Northwest Ethiopia: : A Two-Perspective Analysis
No full textDelay in the diagnosis of tuberculosis (TB) causes more severe illness, more complication and an increased period of infectivity in the community. A study in Amhara region in 2001 showed that, among those who had history of cough of more than 3 weeks, only 30% visited the formal health care facilities. We hypothesized that there was a significant patients and health systems delay in the diagnosis of pulmonary TB in Amhara region, and this study was conducted to test our hypothesis.
Objectives: To determine and analyze the length and associated risk factors of patients health providers and health systems delay among new smear positive pulmonary TB patients in Amhara region, Northwest Ethiopia.
Methods: Within the setting of government health care facilities in Amhara region, we conducted a cross-sectional study from September 1 - December 31/2003. A total of 384 new smear positive pulmonary TB patients participated in the study. Patients were interviewed on the same date of the diagnosis using a semi-structured questionnaire.
Result: The median total delay was 80 days (IQR 44-130 days) and the median patients delay was 30 days (IQR 15-90 days). Forty eight percent of the subjects delayed for more than one month. The median health providers and health systems delays were 61 and 21 days, respectively. In logistics regression, home distance >10 Km to a medical provider (adjusted odds ratio [ORadj] 3.81, 95% confidence interval [CI] 2.21-6.57) and self-treatment (adjusted odds ratio [ORadj] 1.69, 95% confidence interval [CI] 1.86-6.57) were associated with patients delay. Prior attendance to a health post/clinic (adjusted odds ratio [ORadj] 3.50, 95% confidence interval [CI] 1.86-6.57) and consulting private medical providers (adjusted odds ratio [ORadj] 2.10, 95% confidence interval [CI] 1.18-3.71) were associated with increased health systems delay.
Conclusion: Delay in the diagnosis of pulmonary TB is unacceptably high in Amhara region. The delay is primarily related to the health providers. Accessing a simple and rapid diagnostic test for TB at the lowest health care facilities (health post/clinic) and
encouraging a dialogue among all health providers are imperative interventions to reduce health systems delays. Besides these, due emphasis should be given to further decentralization of DOTS to the periphery and increasing public awareness of the disease among the population
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Get PDF“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Get PDFWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Get PDFWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
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