Browsing by Author "Kallenius, Gunilla"

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    Genetic diversity and potential routes of transmission of Mycobacterium bovis in Mozambique
    (Public Library of Science, 2018) Machado, Adelina; Rito, Teresa; Ghebremichael, Solomon; Muhate, Nuelma; Maxhuza, Gabriel; Macuamule, Custodia; Moiane, Ivania; Macucule, Baltazar; Marranangumbe, Angelica Suzana; Baptista, Jorge; Manguele, Joaquim; Koivula, Tuija; Streicher, Elizabeth M.; Warren, Robin Mark; Kallenius, Gunilla; Van Helden, Paul; Correia-Neves, Margarida
    Bovine tuberculosis is a zoonotic disease with largely unknown impact in Africa, with risk factors such as HIV and direct contact with animals or consumption of Mycobacterium bovis infected animal products. In order to understand and quantify this risk and design intervention strategies, good epidemiological studies are needed. Such studies can include molecular typing of M. bovis isolates. The aim of this study was to apply these tools to provide novel information concerning the distribution of bovine tuberculosis in cattle in Mozambique and thereby provide relevant information to guide policy development and strategies to contain the disease in livestock, and reduce the risk associated with transmission to humans. A collection of 178 M. bovis isolates was obtained from cattle in Mozambique. Using spoligotyping and regions of difference analysis, we classified the isolates into clonal complexes, thus reporting the first characterisation of M. bovis strains in this region. Data from MIRU-VNTR typing was used to compare isolates from a number of African countries, revealing a deeply geographically structured diversity of M. bovis. Eastern Africa appears to show high diversity, suggesting deep evolution in that region. The diversity of M. bovis in Africa does not seem to be a function of recent importation of animals, but is probably maintained within each particular region by constant reinfection from reservoir animals. Understanding the transmission routes of M. bovis in Mozambique and elsewhere is essential in order to focus public health and veterinary resources to contain bovine tuberculosis.
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    Geospatial distribution of Mycobacterium tuberculosis genotypes in Africa
    (Public Library of Science, 2018-08-01) Chihota, Violet N.; Niehaus, Antoinette; Streicher, Elizabeth M.; Wang, Xia; Sampson, Samantha L.; Mason, Peter; Kallenius, Gunilla; Mfinanga, Sayoki G.; Pillay, Marnomorney; Klopper, Marisa; Kasongo, Webster; Behr, Marcel A.; Van Pittius, Nicolaas C. Gey; Van Helden, Paul D.; Couvin, David; Rastogi, Nalin; Warren, Robin M.
    Objective: To investigate the distribution of Mycobacterium tuberculosis genotypes across Africa. Methods: The SITVIT2 global repository and PUBMED were searched for spoligotype and published genotype data respectively, of M. tuberculosis from Africa. M. tuberculosis lineages in Africa were described and compared across regions and with those from 7 European and 6 South-Asian countries. Further analysis of the major lineages and sub-lineages using Principal Component analysis (PCA) and hierarchical cluster analysis were done to describe clustering by geographical regions. Evolutionary relationships were assessed using phylogenetic tree analysis. Results: The SITVIT2 global repository and PUBMED were searched for spoligotype and published genotype data respectively, of M. tuberculosis from Africa. M. tuberculosis lineages in Africa were described and compared across regions and with those from 7 European and 6 South-Asian countries. Further analysis of the major lineages and sub-lineages using Principal Component analysis (PCA) and hierarchical cluster analysis were done to describe clustering by geographical regions. Evolutionary relationships were assessed using phylogenetic tree analysis. Results: A total of 14727 isolates from 35 African countries were included in the analysis and of these 13607 were assigned to one of 10 major lineages, whilst 1120 were unknown. There were differences in geographical distribution of major lineages and their sub-lineages with regional clustering. Southern African countries were grouped based on high prevalence of LAM11-ZWE strains; strains which have an origin in Portugal. The grouping of North African countries was due to the high percentage of LAM9 strains, which have an origin in the Eastern Mediterranean region. East African countries were grouped based on Central Asian (CAS) and East-African Indian (EAI) strain lineage possibly reflecting historic sea trade with Asia, while West African Countries were grouped based on Cameroon lineage of unknown origin. A high percentage of the Haarlem lineage isolates were observed in the Central African Republic, Guinea, Gambia and Tunisia, however, a mixed distribution prevented close clustering. Conclusions: This study highlighted that the TB epidemic in Africa is driven by regional epidemics characterized by genetically distinct lineages of M. tuberculosis. M. tuberculosis in these regions may have been introduced from either Europe or Asia and has spread through pastoralism, mining and war. The vast array of genotypes and their associated phenotypes should be considered when designing future vaccines, diagnostics and anti-TB drugs.
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    Margarida Genetic diversity and potential routes of transmission of Mycobacterium bovis in Mozambique
    (Public Library of Science, 2018) Machado, Adelina; Rito, Teresa; Ghebremichael, Solomon; Muhate, Nuelma; Maxhuza, Gabriel; Macuamule, Custodia; Moiane, Ivania; Macucule, Baltazar; Marranangumbe, Angelica Suzana; Baptista, Jorge; Manguele, Joaquim; Koivula, Tuija; Streicher, Elizabeth M.; Warren, Robin Mark; Kallenius, Gunilla; Van Helden, Paul; Correia-Neves, Margarida
    ENGLISH ABSTRACT: Bovine tuberculosis is a zoonotic disease with largely unknown impact in Africa, with risk factors such as HIV and direct contact with animals or consumption of Mycobacterium bovis infected animal products. In order to understand and quantify this risk and design intervention strategies, good epidemiological studies are needed. Such studies can include molecular typing of M. bovis isolates. The aim of this study was to apply these tools to provide novel information concerning the distribution of bovine tuberculosis in cattle in Mozambique and thereby provide relevant information to guide policy development and strategies to contain the disease in livestock, and reduce the risk associated with transmission to humans. A collection of 178 M. bovis isolates was obtained from cattle in Mozambique. Using spoligotyping and regions of difference analysis, we classified the isolates into clonal complexes, thus reporting the first characterisation of M. bovis strains in this region. Data from MIRU-VNTR typing was used to compare isolates from a number of African countries, revealing a deeply geographically structured diversity of M. bovis. Eastern Africa appears to show high diversity, suggesting deep evolution in that region. The diversity of M. bovis in Africa does not seem to be a function of recent importation of animals, but is probably maintained within each particular region by constant reinfection from reservoir animals. Understanding the transmission routes of M. bovis in Mozambique and elsewhere is essential in order to focus public health and veterinary resources to contain bovine tuberculosis.
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    A sensitive urinary lipoarabinomannan test for tuberculosis
    (Public Library of Science, 2015) Hamasur, Beston; Bruchfeld, Judith; Van Helden, Paul; Kallenius, Gunilla; Svenson, Stefan
    We have previously developed a diagnostic test for tuberculosis based on detection of mycobacterial lipoarabinomannan (LAM) in urine. The method depended on a laborious concentration step. We have now developed an easy to perform test based on a magnetic immunoassay platform, utilizing high avidity monoclonal antibodies for the detection of LAM in urine. With this method the analytical sensitivity of the assay was increased 50-100-fold compared to conventional ELISA. In a pilot study of HIV-negative patients with microbiologically verified TB (n=17) and healthy controls (n=22) the sensitivity of the test was 82% and the specificity 100%. This is in stark positive contrast to a range of studies using available commercial tests with polyclonal anti-LAM Abs where the sensitivity of the tests in HIVnegative TB patients was very low.
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    Translational research for tuberculosis elimination : priorities, challenges, and actions
    (Public Library of Science, 2016) Lienhardt, Christian; Lonnroth, Knut; Menzies, Dick; Balasegaram, Manica; Chakaya, Jeremiah; Cobelens, Frank; Cohn, Jennifer; Denkinger, Claudia M.; Evans, Thomas G.; Kallenius, Gunilla; Kaplan, Gilla; Kumar, Ajay M. V.; Matthiessen, Line; Mgone, Charles S.; Mizrahi, Valerie; Mukadi, Ya-diul; Nguyen, Viet Nhung; Nordstrom, Anders; Sizemore, Christine F.; Spigelman, Melvin; Squire, S. Bertel; Swaminathan, Soumya; Van Helden, Paul D.; Zumla, Alimuddin; Weyer, Karin; Weil, Diana; Raviglione, Mario
    Summary Points: • The WHO End TB Strategy, endorsed by the World Health Assembly in May 2014, has the ambitious goal of ending the global tuberculosis (TB) epidemic by 2035, with targets of a 95% decline in deaths due to TB (compared with 2015) and a 90% reduction in incidence of TB to ten cases/100,000 or less and no TB-affected household experiencing catastrophic costs due to TB. • Achieving this goal will only be possible through the development and rapid uptake of new tools, including rapid point-of-care diagnostics, safe and shorter treatment of latent TB infection and disease, and an efficacious TB vaccine, combined with efficient health systems and care provision, and actions on the social determinants of TB. • Research for TB elimination requires an intensification of efforts across a continuum from fundamental research to clinical, epidemiological, implementation, health system, and social science research. • Enhancing research along the full spectrum, from basic to implementation, and strengthening research capacity, particularly in low- and middle-income countries severely affected by the TB epidemics, is crucial for TB elimination. • The creation of a research-enabling environment that fosters and rewards high-quality research requires a broad-based, concerted effort by national governments and international donors to develop and promote TB research and research capacity at the country level and the effective engagement of all stakeholders.