Browsing by Author "Crampin, Amelia C"

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    Open Access
    Community-driven citizen science approach to explore cardiovascular disease risk perception, and develop prevention advocacy strategies in sub-Saharan Africa: a programme protocol
    (2021-02-26) Okop, Kufre J; Murphy, Kathy; Lambert, Estelle V; Kedir, Kiya; Getachew, Hailemichael; Howe, Rawleigh; Niyibizi, Jean B; Ntawuyirushintege, Selemani; Bavuma, Charlotte; Rulisa, Stephen; Kasenda, Stephen; Chipeta, Effie; Bunn, Christopher; Crampin, Amelia C; Chapotera, Gertrude; King, Abby C; Banchoff, Ann; Winter, Sandra J; Levitt, Naomi S
    Background In sub-Saharan Africa (SSA), which experiences a disproportionately high cardiovascular disease (CVD) burden, population-based screening and prevention measures are hampered by low levels of knowledge about CVD and associated risk factors, and inaccurate perceptions of severity of risk. Methods This protocol describes the planned processes for implementing community-driven participatory research, using a citizen science method to explore CVD risk perceptions and to develop community-specific advocacy and prevention strategies in the rural and urban SSA settings. Multi-disciplinary research teams in four selected African countries will engage with and train community members living in rural and urban communities as citizen scientists to facilitate conceptualization, co-designing of research, data gathering, and co-creation of knowledge that can lead to a shared agenda to support collaborative participation in community-engaged science. The emphasis is on robust community engagement, using mobile technology to support data gathering, participatory learning, and co-creation of knowledge and disease prevention advocacy. Discussion Contextual processes applied and lessons learned in specific settings will support redefining or disassembling boundaries in participatory science to foster effective implementation of sustainable prevention intervention programmes in Low- and Middle-income countries.
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    Detection of tuberculosis in HIV-infected and-uninfected African adults using whole blood RNA expression signatures: a case-control study
    (Public Library of Science, 2013) Kaforou, Myrsini; Wright, Victoria J; Oni, Tolu; French, Neil; Anderson, Suzanne T; Bangani, Nonzwakazi; Banwell, Claire M; Brent, Andrew J; Crampin, Amelia C; Dockrell, Hazel M
    Background: A major impediment to tuberculosis control in Africa is the difficulty in diagnosing active tuberculosis (TB), particularly in the context of HIV infection. We hypothesized that a unique host blood RNA transcriptional signature would distinguish TB from other diseases (OD) in HIV-infected and -uninfected patients, and that this could be the basis of a simple diagnostic test. Methods and Findings: Adult case-control cohorts were established in South Africa and Malawi of HIV-infected or -uninfected individuals consisting of 584 patients with either TB (confirmed by culture of Mycobacterium tuberculosis [M.TB] from sputum or tissue sample in a patient under investigation for TB), OD (i.e., TB was considered in the differential diagnosis but then excluded), or healthy individuals with latent TB infection (LTBI). Individuals were randomized into training (80%) and test (20%) cohorts. Blood transcriptional profiles were assessed and minimal sets of significantly differentially expressed transcripts distinguishing TB from LTBI and OD were identified in the training cohort. A 27 transcript signature distinguished TB from LTBI and a 44 transcript signature distinguished TB from OD. To evaluate our signatures, we used a novel computational method to calculate a disease risk score (DRS) for each patient. The classification based on this score was first evaluated in the test cohort, and then validated in an independent publically available dataset (GSE19491). In our test cohort, the DRS classified TB from LTBI (sensitivity 95%, 95% CI [87–100]; specificity 90%, 95% CI [80–97]) and TB from OD (sensitivity 93%, 95% CI [83–100]; specificity 88%, 95% CI [74–97]). In the independent validation cohort, TB patients were distinguished both from LTBI individuals (sensitivity 95%, 95% CI [85–100]; specificity 94%, 95% CI [84–100]) and OD patients (sensitivity 100%, 95% CI [100–100]; specificity 96%, 95% CI [93–100]). Limitations of our study include the use of only culture confirmed TB patients, and the potential that TB may have been misdiagnosed in a small proportion of OD patients despite the extensive clinical investigation used to assign each patient to their diagnostic group. Conclusions: In our study, blood transcriptional signatures distinguished TB from other conditions prevalent in HIV-infected and -uninfected African adults. Our DRS, based on these signatures, could be developed as a test for TB suitable for use in HIV endemic countries. Further evaluation of the performance of the signatures and DRS in prospective populations of patients with symptoms consistent with TB will be needed to define their clinical value under operational conditions.
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    Recombination in pe/ppe genes contributes to genetic variation in Mycobacterium tuberculosis lineages
    (BioMed Central, 2016-02-29) Phelan, Jody E; Coll, Francesc; Bergval, Indra; Anthony, Richard M; Warren, Rob; Sampson, Samantha L; Gey van Pittius, Nicolaas C; Glynn, Judith R; Crampin, Amelia C; Alves, Adriana; Bessa, Theolis B; Campino, Susana; Dheda, Keertan; Grandjean, Louis; Hasan, Rumina; Hasan, Zahra; Miranda, Anabela; Moore, David; Panaiotov, Stefan; Perdigao, Joao; Portugal, Isabel; Sheen, Patricia; de Oliveira Sousa, Erivelton; Streicher, Elizabeth M; van Helden, Paul D; Viveiros, Miguel; Hibberd, Martin L; Pain, Arnab; McNerney, Ruth; Clark, Taane G
    Background: Approximately 10 % of the Mycobacterium tuberculosis genome is made up of two families of genes that are poorly characterized due to their high GC content and highly repetitive nature. The PE and PPE families are typified by their highly conserved N-terminal domains that incorporate proline-glutamate (PE) and proline-proline-glutamate (PPE) signature motifs. They are hypothesised to be important virulence factors involved with host-pathogen interactions, but their high genetic variability and complexity of analysis means they are typically disregarded in genome studies. Results: To elucidate the structure of these genes, 518 genomes from a diverse international collection of clinical isolates were de novo assembled. A further 21 reference M. tuberculosis complex genomes and long read sequence data were used to validate the approach. SNP analysis revealed that variation in the majority of the 168 pe/ppe genes studied was consistent with lineage. Several recombination hotspots were identified, notably pe_pgrs3 and pe_pgrs17. Evidence of positive selection was revealed in 65 pe/ppe genes, including epitopes potentially binding to major histocompatibility complex molecules. Conclusions: This, the first comprehensive study of the pe and ppe genes, provides important insight into M. tuberculosis diversity and has significant implications for vaccine development.