Browsing by Author "Kranzer, Katharina"

Now showing 1 - 3 of 3
  • Thumbnail Image
    Item
    High prevalence of self-reported undiagnosed HIV despite high coverage of HIV testing : a cross-sectional population based sero-survey in South Africa
    (Public Library of Science, 2011-09-28) Kranzer, Katharina; Van Schaik, Nienke; Karmue, Unice; Middelkoop, Keren; Sebastian, Elaine; Lawn, Stephen D.; Wood, Robiin; Bekker, Linda-Gail
    Objectives To measure HIV prevalence and uptake of HIV counseling and testing (HCT) in a peri-urban South African community. To assess predictors for previous HIV testing and the association between the yield of previously undiagnosed HIV and time of last negative HIV test Methods A random sample of 10% of the adult population (≥15 years) were invited to attend a mobile HCT service. Study procedures included a questionnaire, HIV testing and CD4 counts. Predictors for previous testing were determined using a binominal model. Results 1,144 (88.0%) of 1,300 randomly selected individuals participated in the study. 71.0% (68.3–73.6) had previously had an HIV test and 37.5% (34.6–40.5) had tested in the past 12 months. Men, migrants and older (>35 years) and younger (<20 years) individuals were less likely to have had a previous HIV test. Overall HIV prevalence was 22.7 (20.3–25.3) with peak prevalence of 41.8% (35.8–47.8) in women aged 25.1–35 years and 37.5% (26.7–48.3) in men aged 25.1–45 years. Prevalence of previously undiagnosed HIV was 10.3% (8.5–12.1) overall and 4.5% (2.3–6.6), 8.0% (CI 3.9–12.0) and 20.0% (13.2–26.8) in individuals who had their most recent HIV test within 1, 1–2 and more than 2 years prior to the survey. Conclusion The high burden of undiagnosed HIV in individuals who had recently tested underscores the importance of frequent repeat testing at least annually. The high prevalence of previously undiagnosed HIV in individuals reporting a negative test in the 12 months preceding the survey indicates a very high incidence. Innovative prevention strategies are needed.
  • Thumbnail Image
    Item
    MDR M. tuberculosis outbreak clone in Eswatini missed by Xpert has elevated bedaquiline resistance dated to the pre-treatment era
    (BMC, 2020-11-25) Beckert, Patrick; Sanchez-Padilla, Elisabeth; Merker, Matthias; Dreyer, Viola; Kohl, Thomas A.; Utpatel, Christian; Koser, Claudio U.; Barilar, Ivan; Ismail, Nazir; Omar, Shaheed V.; Klopper, Marisa; Warren, Robin M.; Hoffmann, Harald; Maphalala, Gugu; Ardizzoni, Elisa; De Jong, Bouke C.; Kerschberger, Bernhard; Schramm, Birgit; Andres, Sonke; Kranzer, Katharina; Maurer, Florian P.; Bonnet, Maryline; Niemann, Stefan
    Background: Multidrug-resistant (MDR) Mycobacterium tuberculosis complex strains not detected by commercial molecular drug susceptibility testing (mDST) assays due to the RpoB I491F resistance mutation are threatening the control of MDR tuberculosis (MDR-TB) in Eswatini. Methods: We investigate the evolution and spread of MDR strains in Eswatini with a focus on bedaquiline (BDQ) and clofazimine (CFZ) resistance using whole-genome sequencing in two collections ((1) national drug resistance survey, 2009–2010; (2) MDR strains from the Nhlangano region, 2014–2017). Results: MDR strains in collection 1 had a high cluster rate (95%, 117/123 MDR strains) with 55% grouped into the two largest clusters (gCL3, n = 28; gCL10, n = 40). All gCL10 isolates, which likely emerged around 1993 (95% highest posterior density 1987–1998), carried the mutation RpoB I491F that is missed by commercial mDST assays. In addition, 21 (53%) gCL10 isolates shared a Rv0678 M146T mutation that correlated with elevated minimum inhibitory concentrations (MICs) to BDQ and CFZ compared to wild type isolates. gCL10 isolates with the Rv0678 M146T mutation were also detected in collection 2. Conclusion: The high clustering rate suggests that transmission has been driving the MDR-TB epidemic in Eswatini for three decades. The presence of MDR strains in Eswatini that are not detected by commercial mDST assays and have elevated MICs to BDQ and CFZ potentially jeopardizes the successful implementation of new MDR-TB treatment guidelines. Measures to limit the spread of these outbreak isolates need to be implemented urgently.
  • Thumbnail Image
    Item
    Screening for HIV-associated tuberculosis and rifampicin resistance before antiretroviral therapy using the Xpert MTB/RIF assay : a prospective study
    (Public Library of Science, 2011-07-26) Lawn, Stephen D.; Brooks, Sophie V.; Kranzer, Katharina; Nicol, Mark P.; Whitelaw, Andrew; Vogt, Monica; Bekker, Linda-Gail; Wood, Robin
    Background: The World Health Organization has endorsed the Xpert MTB/RIF assay for investigation of patients suspected of having tuberculosis (TB). However, its utility for routine TB screening and detection of rifampicin resistance among HIV-infected patients with advanced immunodeficiency enrolling in antiretroviral therapy (ART) services is unknown. Methods and Findings: Consecutive adult HIV-infected patients with no current TB diagnosis enrolling in an ART clinic in a South African township were recruited regardless of symptoms. They were clinically characterised and invited to provide two sputum samples at a single visit. The accuracy of the Xpert MTB/RIF assay for diagnosing TB and drug resistance was assessed in comparison with other tests, including fluorescence smear microscopy and automated liquid culture (gold standard) and drug susceptibility testing. Of 515 patients enrolled, 468 patients (median CD4 cell count, 171 cells/μl; interquartile range, 102-236) produced at least one sputum sample, yielding complete sets of results from 839 samples. Mycobacterium tuberculosis was cultured from 81 patients (TB prevalence, 17.3%). The overall sensitivity of the Xpert MTB/RIF assay for culture-positive TB was 73.3% (specificity, 99.2%) compared to 28.0% (specificity, 100%) using smear microscopy. All smear-positive, culture-positive disease was detected by Xpert MTB/RIF from a single sample (sensitivity, 100%), whereas the sensitivity for smear-negative, culture-positive TB was 43.4% from one sputum sample and 62.3% from two samples. Xpert correctly identified rifampicin resistance in all four cases of multidrug-resistant TB but incorrectly identified resistance in three other patients whose disease was confirmed to be drug sensitive by gene sequencing (specificity, 94.1%; positive predictive value, 57%). Conclusions: In this population of individuals at high risk of TB, intensive screening using the Xpert MTB/RIF assay increased case detection by 45% compared with smear microscopy, strongly supporting replacement of microscopy for this indication. However, despite the ability of the assay to rapidly detect rifampicin-resistant disease, the specificity for drug-resistant TB was sub-optimal. © 2011 Lawn et al.