Browsing by Author "Warren, Robin"

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    High yield of culture-based diagnosis in a TB-endemic setting
    (BioMed Central, 2012-09) Demers, Anne-Marie; Verver, Suzanne; Boulle, Andrew; Warren, Robin; Van Helden, Paul; Behr, Marcel A.; Coetzee, David
    Abstract Background In most of the world, microbiologic diagnosis of tuberculosis (TB) is limited to microscopy. Recent guidelines recommend culture-based diagnosis where feasible. Methods In order to evaluate the relative and absolute incremental diagnostic yield of culture-based diagnosis in a high-incidence community in Cape Town, South Africa, subjects evaluated for suspected TB had their samples processed for microscopy and culture over a 21 month period. Results For 2537 suspect episodes with 2 smears and 2 cultures done, 20.0% (508) had at least one positive smear and 29.9% (760) had at least one positive culture. One culture yielded 1.8 times more cases as 1 smear (relative yield), or an increase of 12.0% (absolute yield). Based on the latter value, the number of cultures needed to diagnose (NND) one extra case of TB was 8, compared to 19 if second specimens were submitted for microscopy. Conclusion In a high-burden setting, the introduction of culture can markedly increase TB diagnosis over microscopy. The concept of number needed to diagnose can help in comparing incremental yield of diagnosis methods. Although new promising diagnostic molecular methods are being implemented, TB culture is still the gold standard.
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    Mycobacterium tuberculosis complex genetic diversity : mining the fourth international spoligotyping database (SpolDB4) for classification, population genetics and epidemiology
    (2006-03) Brudey, Karine; Driscoll, Jeffrey R.; Rigouts, Leen; Prodinger, Wolfgang M.; Gori, Andrea; Al-Hajoj, Sahal A. M.; Allix, Caroline; Aristimuno, Liselotte; Arora, Jyoti; Baumanis, Viesturs; Binder, Lothar; Cafrune, Patricia; Cataldi, Angel; Cheong, Soonfatt; Diel, Roland; Ellermeier, Christopher; Evans, Jason T.; Fauville-Dufaux, Maryse; Ferdinand, Severine; Garcia de Viedma, Dario; Garzelli, Carlo; Gazzola, Lidia; Gomes, Harrison M.; Gutierrez, M. Cristina; Hawkey, Peter M.; Van Helden, Paul D.; Kadival, Gurujaj V.; Kreiswirth, Barry N.; Kremer, Kristin; Kubin, Milan; Kulkarni, Savita P.; Liens, Benjamin; Lillebaek, Troels; Ly, Ho Minh; Martin, Carlos; Martin, Christian; Mokrousov, Igor; Narvskaia, Olga; Ngeow, Yun Fong; Naumann, Ludmilla; Niemann, Stefan; Parwati, Ida; Rahim, Mohammad Z.; Rasolofo-Razanamparany, Voahangy; Rasolonavalona, Tiana; Rossetti, M. Lucia; Rusch-Gerdes, Sabine; Sajduda, Anna; Samper, Sofia; Shemyakin, Igor; Singh, Urvashi B.; Somoskovi, Akos; Skuce, Robin; Van Soolingen, Dick; Streicher, Elizabeth M.; Suffys, Philip N.; Tortoli, Enrico; Tracevska, Tatjana; Vincent, Veronique; Victor, Tommie C.; Warren, Robin; Yap, Sook Fan; Zaman, Kadiza; Portaels, Francoise; Rastogi, Nalin; Sola, Christophe
    Background: The Direct Repeat locus of the Mycobacterium tuberculosis complex (MTC) is a member of the CRISPR (Clustered regularly interspaced short palindromic repeats) sequences family. Spoligotyping is the widely used PCR-based reverse-hybridization blotting technique that assays the genetic diversity of this locus and is useful both for clinical laboratory, molecular epidemiology, evolutionary and population genetics. It is easy, robust, cheap, and produces highly diverse portable numerical results, as the result of the combination of (1) Unique Events Polymorphism (UEP) (2) Insertion-Sequence-mediated genetic recombination. Genetic convergence, although rare, was also previously demonstrated. Three previous international spoligotype databases had partly revealed the global and local geographical structures of MTC bacilli populations, however, there was a need for the release of a new, more representative and extended, international spoligotyping database. Results: The fourth international spoligotyping database, SpolDB4, describes 1939 shared-types (STs) representative of a total of 39,295 strains from 122 countries, which are tentatively classified into 62 clades/lineages using a mixed expert-based and bioinformatical approach. The SpolDB4 update adds 26 new potentially phylogeographically-specific MTC genotype families. It provides a clearer picture of the current MTC genomes diversity as well as on the relationships between the genetic attributes investigated (spoligotypes) and the infra-species classification and evolutionary history of the species. Indeed, an independent Naïve-Bayes mixture-model analysis has validated main of the previous supervised SpolDB3 classification results, confirming the usefulness of both supervised and unsupervised models as an approach to understand MTC population structure. Updated results on the epidemiological status of spoligotypes, as well as genetic prevalence maps on six main lineages are also shown. Our results suggests the existence of fine geographical genetic clines within MTC populations, that could mirror the passed and present Homo sapiens sapiens demographical and mycobacterial co-evolutionary history whose structure could be further reconstructed and modelled, thereby providing a large-scale conceptual framework of the global TB Epidemiologic Network. Conclusion: Our results broaden the knowledge of the global phylogeography of the MTC complex. SpolDB4 should be a very useful tool to better define the identity of a given MTC clinical isolate, and to better analyze the links between its current spreading and previous evolutionary history. The building and mining of extended MTC polymorphic genetic databases is in progress.
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    Rifampicin resistant tuberculosis in Lesotho : diagnosis, treatment initiation and outcomes
    (Nature Research [Commercial Publisher], 2019-12) Katende, Bulemba; Esterhuizen, Tonya; Dippenaar, Anzaan; Warren, Robin; Warren, Robin Mark
    The Lesotho guidelines for the management of drug-resistant tuberculosis (TB) recommend initiation of patients diagnosed with rifampicin resistant (RR)-TB on a standardized drug resistant regimen while awaiting confirmation of rifampicin resistant TB (RR-TB) and complete drug susceptibility test results. Review of diagnostic records between 2014 and 2016 identified 518 patients with RR-TB. Only 314 (60.6%) patients could be linked to treatment records at the Lesotho MDR hospital. The median delay in treatment initiation from the availability of Xpert MTB/RIF assay result was 12 days (IQR 7–19). Only 32% (101) of patients had a documented first-line drug resistant test. MDR-TB was detected in 56.4% of patients while 33.7% of patients had rifampicin mono-resistance. Only 7.4% of patients assessed for second-line resistance had a positive result (resistance to fluoroquinolone). Treatment success was 69.8%, death rate was 28.8%, loss to follow up was 1.0%, and 0.4% failed treatment. Death was associated with positive or unavailable sputum smear at the end of first month of treatment (Fisher exact p < 0.001) and older age (p = 0.007). Urgent attention needs to be given to link patients with RR-TB to care worldwide. The association of death rate with positive sputum smear at the end of the first month of treatment should trigger early individualization of treatment.