The Experts below are selected from a list of 303 Experts worldwide ranked by ideXlab platform
Hypolite Muhindo Mavoko - One of the best experts on this subject based on the ideXlab platform.
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Uncomplicated Clinical Malaria Features, the Efficacy of Artesunate-Amodiaquine and Their Relation with Multiplicity of Infection in the Democratic Republic of Congo.
PLOS ONE, 2016Co-Authors: Hypolite Muhindo Mavoko, Marion Kalabuanga, Christopher Delgado-ratto, Vivi Maketa, Rodin Mukele, Blaise Fungula, Anna Rosanas-urgell, Pascal Lutumba, Jean-pierre Van GeertruydenAbstract:Background In the Democratic Republic of Congo, artesunate-amodiaquine (ASAQ) is the first-line medication recommended for uncomplicated malaria treatment. We conducted a study in Kinshasa to describe the clinical features of the disease and assess the efficacy of ASAQ and its impact on the Multiplicity of Infection in children with uncomplicated malaria. Methods Children aged 12 to 59 months with uncomplicated P. falciparum malaria were treated with ASAQ and followed up passively for 42 days. To distinguish new Infections from recrudescent parasites, samples were genotyped using a stepwise strategy with three molecular markers (GLURP, MSP2 and MSP1). We then assessed PCR-corrected and -uncorrected day-42 cure rates and Multiplicity of Infection (MOI). Results In total, 2,796 patients were screened and 865 enrolled in the study. Clinical features were characterized by history of fever (100%), coryza (59.9%) and weakness (59.4%). The crude and PCR-corrected efficacies of ASAQ were 55.3% (95%CI: 51.8–58.8) and 92.8% (95%CI: 91.0–94.6) respectively, as 83.6% (95%CI: 79.1–87.2) of the recurrences were new Infections. Compared to monoclonal Infections, polyclonal Infections were more frequent at enrollment (88.1%) and in recurrences (80.1%; p = 0.005; OR: 1.8, 95%CI: 1.20–2.8). The median MOI at enrollment (MOI = 3.7; IQR: 0.7–6.7) decreased to 3 (IQR: 1–5) in the recurrent samples (p
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uncomplicated clinical malaria features the efficacy of artesunate amodiaquine and their relation with Multiplicity of Infection in the democratic republic of congo
PLOS ONE, 2016Co-Authors: Hypolite Muhindo Mavoko, Marion Kalabuanga, Vivi Maketa, Rodin Mukele, Blaise Fungula, Christopher Delgadoratto, Anna Rosanasurgell, Pascal LutumbaAbstract:Background In the Democratic Republic of Congo, artesunate-amodiaquine (ASAQ) is the first-line medication recommended for uncomplicated malaria treatment. We conducted a study in Kinshasa to describe the clinical features of the disease and assess the efficacy of ASAQ and its impact on the Multiplicity of Infection in children with uncomplicated malaria. Methods Children aged 12 to 59 months with uncomplicated P. falciparum malaria were treated with ASAQ and followed up passively for 42 days. To distinguish new Infections from recrudescent parasites, samples were genotyped using a stepwise strategy with three molecular markers (GLURP, MSP2 and MSP1). We then assessed PCR-corrected and -uncorrected day-42 cure rates and Multiplicity of Infection (MOI). Results In total, 2,796 patients were screened and 865 enrolled in the study. Clinical features were characterized by history of fever (100%), coryza (59.9%) and weakness (59.4%). The crude and PCR-corrected efficacies of ASAQ were 55.3% (95%CI: 51.8–58.8) and 92.8% (95%CI: 91.0–94.6) respectively, as 83.6% (95%CI: 79.1–87.2) of the recurrences were new Infections. Compared to monoclonal Infections, polyclonal Infections were more frequent at enrollment (88.1%) and in recurrences (80.1%; p = 0.005; OR: 1.8, 95%CI: 1.20–2.8). The median MOI at enrollment (MOI = 3.7; IQR: 0.7–6.7) decreased to 3 (IQR: 1–5) in the recurrent samples (p<0.001). Patients infected with a single haplotype on day 0 had no recrudescence; the risk of recrudescence increased by 28% with each additional haplotype (HR: 1.3, 95%CI: 1.24–1.44). Conclusion The PCR-corrected efficacy of ASAQ at day 42 was 92.8%, but crude efficacy was relatively poor due to high reInfection rates. Treatment outcomes were positively correlated with MOI. Continued monitoring of the efficacy of ACTs—ASAQ, in this case—is paramount. Trial Registration ClinicalTrials.gov NCT01374581
Andrew Tait - One of the best experts on this subject based on the ideXlab platform.
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population diversity of theileria annulata in portugal
Infection Genetics and Evolution, 2016Co-Authors: Jacinto Gomes, Brian Shiels, Patricia Salgueiro, Joao Pinto, Isabel Pereira Da Fonseca, Ana Amaro, Andrew Tait, Joao Inacio, Gabriela SantosgomesAbstract:The tick-borne protozoan parasite Theileria annulata causes tropical theileriosis, a severe disease of cattle that occurs across the Mediterranean littoral, the Middle East and Southern Asia. In the Mediterranean region, the disease has long been perceived as being a constraint to livestock production in North Africa and Turkey but was believed to have minimal impact in Southern European countries. It has recently been demonstrated that in Southern Portugal the prevalence of T. annulata is approximately 30%. While the population genetics of the parasite and the Multiplicity of Infection in the bovine host have been studied in a number of countries, no information is currently available on the composition of the parasite population in Southern Europe or its relationship to populations in bordering regions. A parasite genotyping system, based on micro- and mini-satellite amplification, was used to perform genetic analysis of T. annulata populations from T. annulata infected cattle in twelve farms in Southern Portugal. A diversity of genotypes and a high Multiplicity of Infection were found, suggesting that the parasite possesses a panmictic population in this region. In comparison with genotypes found in Tunisia and Turkey, parasites from Portugal form a genetically distinct group and show lower genetic diversity.
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population diversity and Multiplicity of Infection in theileria annulata
International Journal for Parasitology, 2011Co-Authors: William Weir, Brian Shiels, Tulin Karagenc, Mohamed Gharbi, Martin Simuunza, Suleyman Aypak, Nuran Aysul, Mohamed Aziz Darghouth, Andrew TaitAbstract:The tick-borne apicomplexan parasite Theileria annulata is endemic in many sub-tropical countries and causes the bovine disease tropical theileriosis. Although the parasite is known to be highly diverse, detailed information is lacking on the genetic structure of natural populations and levels of Multiplicity of Infection in the cattle host. With the widespread deployment of live attenuated vaccines and the emergence of drug-resistant parasites in the field, it is vital to appreciate the factors which shape genetic diversity of the parasite both within individual hosts and in the wider population. This study addresses these issues and represents an extensive genetic analysis of T. annulata populations in two endemic countries utilising a high-throughput adaptation of a micro- and mini-satellite genotyping system. Parasite material was collected from infected cattle in defined regions of Turkey and Tunisia to allow a variety of analyses to be conducted. All animals (n = 305) were found to harbour multiple parasite genotypes and only two isolates shared an identical predominant multi-locus profile. A modelling approach was used to demonstrate that host age, location and vaccination status play a measurable role in determining Multiplicity of Infection in an individual animal. Age was shown to positively correlate with Multiplicity of Infection and while positive vaccination status exerted a similar effect, it was shown to be due not simply to the presence of the immunising genotype. Importantly, no direct evidence was found for the immunising genotype spreading or recombining within the local parasite community. Genetic analysis confirmed the tentative conclusion of a previous study that the parasite population appears to be, in general, panmictic. Nevertheless, evidence supporting linkage disequilibrium and a departure from panmixia was uncovered in some localities and a number of explanations for these findings are advanced.
Helmut Hanenberg - One of the best experts on this subject based on the ideXlab platform.
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in vivo selection of hematopoietic stem cells transduced at a low Multiplicity of Infection with a foamy viral mgmtp140k vector
Experimental Hematology, 2008Co-Authors: Aaron Ernstberger, Haiyan Wang, Barbara J Bailey, Jennifer R Hartwell, Anthony L Sinn, Olaf Eckermann, Yvonne Linka, Scott W Goebel, Helmut HanenbergAbstract:Objective Using a clinically relevant transduction strategy, we investigated to what extent hematopoietic stem cells in lineage-negative bone marrow (Lin neg BM) could be genetically modified with an foamy virus (FV) vector that expresses the DNA repair protein, O 6 -methylguanine DNA methyltransferase (MGMT P140K ) and selected in vivo with submyeloablative or myeloablative alkylator therapy. Materials and Methods Lin neg BM was transduced at a low Multiplicity-of-Infection with the FV vector, MD9-P140K, which coexpresses MGMT P140K and the enhanced green fluorescent protein, transplanted into C57BL/6 mice, and mice treated with submyeloablative or myeloablative alkylator therapy. The BM was analyzed for the presence of in vivo selected, MD9-P140K–transduced cells at 6 months post-transplantation and subsequently transplanted into secondary recipient animals. Results Following submyeloablative therapy, 55% of the mice expressed MGMT P140K in the BM. Proviral integration was observed in ∼50% of committed BM-derived progenitors and analysis of proviral insertion sites indicated up to two integrations per transduced progenitor colony. Transduced BM cells selected with submyeloablative therapy reconstituted secondary recipient mice for up to 6 months post-transplantation. In contrast, after delivery of myeloablative therapy to primary recipient mice, only 25% survived. Hematopoietic stem cells were transduced because BM cells from the surviving animals reconstituted secondary recipients with MGMT P140K -positive cells for 5 to 6 months. Conclusions In vivo selection of MD9-P140K–transduced BM cells was more efficient following submyeloablative than myeloablative therapy. These data indicate that a critical number of transduced stem cells must be present to produce sufficient numbers of genetically modified progeny to protect against acute toxicity associated with myeloablative therapy.
Christopher Baum - One of the best experts on this subject based on the ideXlab platform.
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influence of Multiplicity of Infection and protein stability on retroviral vector mediated gene expression in hematopoietic cells
Gene Therapy, 2001Co-Authors: Anke Wahlers, Maike Schwieger, Zhixiong Li, D Meiertackmann, C Lindemann, H G Eckert, D Von Laer, Christopher BaumAbstract:Using retroviral vectors encoding enhanced green fluorescent protein (egfp), we addressed to what extent expression of retroviral transgenes in hematopoietic cells depends on the Multiplicity of Infection (moi) and on the half-life of the encoded protein. we show that an elevation of the moi not only elevates the frequency of transduced cells, but also increases transgene expression levels and reduces interanimal variability in vivo (hematopoietic cells of c57bl/6j mice analyzed 13 weeks after transplantation). this suggests that the moi has to be carefully controlled and should be adapted as desired for clinical studies when evaluating vector performance in preclinical models. the impact of protein stability is demonstrated by comparing vectors expressing egfp or a destabilized variant with a c-terminal pest-sequence, d2egfp. the loss of expression with d2egfp was more pronounced in terminally differentiated cells of the peripheral blood (>30 fold) than in progenitor cells (five- to 10-fold), indicating a stronger transcription of the retroviral promoter in progenitor cells and a predominant role of protein inheritance over de novo synthesis of transgenic protein in mature blood cells. This analysis reveals an important and differentiation-dependent contribution of protein half-life to the expression of retroviral vectors in hematopoietic cells, establishes d2EGFP as a more accurate reporter for determination of vector transcription, and also suggests that preclinical data obtained under conditions of high transduction rates or with vectors expressing stable reporter proteins require careful interpretation.
Pascal Lutumba - One of the best experts on this subject based on the ideXlab platform.
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Uncomplicated Clinical Malaria Features, the Efficacy of Artesunate-Amodiaquine and Their Relation with Multiplicity of Infection in the Democratic Republic of Congo.
PLOS ONE, 2016Co-Authors: Hypolite Muhindo Mavoko, Marion Kalabuanga, Christopher Delgado-ratto, Vivi Maketa, Rodin Mukele, Blaise Fungula, Anna Rosanas-urgell, Pascal Lutumba, Jean-pierre Van GeertruydenAbstract:Background In the Democratic Republic of Congo, artesunate-amodiaquine (ASAQ) is the first-line medication recommended for uncomplicated malaria treatment. We conducted a study in Kinshasa to describe the clinical features of the disease and assess the efficacy of ASAQ and its impact on the Multiplicity of Infection in children with uncomplicated malaria. Methods Children aged 12 to 59 months with uncomplicated P. falciparum malaria were treated with ASAQ and followed up passively for 42 days. To distinguish new Infections from recrudescent parasites, samples were genotyped using a stepwise strategy with three molecular markers (GLURP, MSP2 and MSP1). We then assessed PCR-corrected and -uncorrected day-42 cure rates and Multiplicity of Infection (MOI). Results In total, 2,796 patients were screened and 865 enrolled in the study. Clinical features were characterized by history of fever (100%), coryza (59.9%) and weakness (59.4%). The crude and PCR-corrected efficacies of ASAQ were 55.3% (95%CI: 51.8–58.8) and 92.8% (95%CI: 91.0–94.6) respectively, as 83.6% (95%CI: 79.1–87.2) of the recurrences were new Infections. Compared to monoclonal Infections, polyclonal Infections were more frequent at enrollment (88.1%) and in recurrences (80.1%; p = 0.005; OR: 1.8, 95%CI: 1.20–2.8). The median MOI at enrollment (MOI = 3.7; IQR: 0.7–6.7) decreased to 3 (IQR: 1–5) in the recurrent samples (p
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uncomplicated clinical malaria features the efficacy of artesunate amodiaquine and their relation with Multiplicity of Infection in the democratic republic of congo
PLOS ONE, 2016Co-Authors: Hypolite Muhindo Mavoko, Marion Kalabuanga, Vivi Maketa, Rodin Mukele, Blaise Fungula, Christopher Delgadoratto, Anna Rosanasurgell, Pascal LutumbaAbstract:Background In the Democratic Republic of Congo, artesunate-amodiaquine (ASAQ) is the first-line medication recommended for uncomplicated malaria treatment. We conducted a study in Kinshasa to describe the clinical features of the disease and assess the efficacy of ASAQ and its impact on the Multiplicity of Infection in children with uncomplicated malaria. Methods Children aged 12 to 59 months with uncomplicated P. falciparum malaria were treated with ASAQ and followed up passively for 42 days. To distinguish new Infections from recrudescent parasites, samples were genotyped using a stepwise strategy with three molecular markers (GLURP, MSP2 and MSP1). We then assessed PCR-corrected and -uncorrected day-42 cure rates and Multiplicity of Infection (MOI). Results In total, 2,796 patients were screened and 865 enrolled in the study. Clinical features were characterized by history of fever (100%), coryza (59.9%) and weakness (59.4%). The crude and PCR-corrected efficacies of ASAQ were 55.3% (95%CI: 51.8–58.8) and 92.8% (95%CI: 91.0–94.6) respectively, as 83.6% (95%CI: 79.1–87.2) of the recurrences were new Infections. Compared to monoclonal Infections, polyclonal Infections were more frequent at enrollment (88.1%) and in recurrences (80.1%; p = 0.005; OR: 1.8, 95%CI: 1.20–2.8). The median MOI at enrollment (MOI = 3.7; IQR: 0.7–6.7) decreased to 3 (IQR: 1–5) in the recurrent samples (p<0.001). Patients infected with a single haplotype on day 0 had no recrudescence; the risk of recrudescence increased by 28% with each additional haplotype (HR: 1.3, 95%CI: 1.24–1.44). Conclusion The PCR-corrected efficacy of ASAQ at day 42 was 92.8%, but crude efficacy was relatively poor due to high reInfection rates. Treatment outcomes were positively correlated with MOI. Continued monitoring of the efficacy of ACTs—ASAQ, in this case—is paramount. Trial Registration ClinicalTrials.gov NCT01374581
