African Academy of science

Nairobi, Kenya

African Academy of science

Nairobi, Kenya
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White M.T.,Imperial College London | Verity R.,Imperial College London | Griffin J.T.,Imperial College London | Asante K.P.,Kintampo Health Research Center | And 40 more authors.
The Lancet Infectious Diseases | Year: 2015

Background: The RTS,S/AS01 malaria vaccine targets the circumsporozoite protein, inducing antibodies associated with the prevention of Plasmodium falciparum infection. We assessed the association between anti-circumsporozoite antibody titres and the magnitude and duration of vaccine efficacy using data from a phase 3 trial done between 2009 and 2014. Methods: Using data from 8922 African children aged 5-17 months and 6537 African infants aged 6-12 weeks at first vaccination, we analysed the determinants of immunogenicity after RTS,S/AS01 vaccination with or without a booster dose. We assessed the association between the incidence of clinical malaria and anti-circumsporozoite antibody titres using a model of anti-circumsporozoite antibody dynamics and the natural acquisition of protective immunity over time. Findings: RTS,S/AS01-induced anti-circumsporozoite antibody titres were greater in children aged 5-17 months than in those aged 6-12 weeks. Pre-vaccination anti-circumsporozoite titres were associated with lower immunogenicity in children aged 6-12 weeks and higher immunogenicity in those aged 5-17 months. The immunogenicity of the booster dose was strongly associated with immunogenicity after primary vaccination. Anti-circumsporozoite titres wane according to a biphasic exponential distribution. In participants aged 5-17 months, the half-life of the short-lived component of the antibody response was 45 days (95% credible interval 42-48) and that of the long-lived component was 591 days (557-632). After primary vaccination 12% (11-13) of the response was estimated to be long-lived, rising to 30% (28-32%) after a booster dose. An anti-circumsporozoite antibody titre of 121 EU/mL (98-153) was estimated to prevent 50% of infections. Waning anti-circumsporozoite antibody titres predict the duration of efficacy against clinical malaria across different age categories and transmission intensities, and efficacy wanes more rapidly at higher transmission intensity. Interpretation: Anti-circumsporozoite antibody titres are a surrogate of protection for the magnitude and duration of RTS,S/AS01 efficacy, with or without a booster dose, providing a valuable surrogate of effectiveness for new RTS,S formulations in the age groups considered. Funding: UK Medical Research Council. © 2015 White et al. Open Access article distributed under the terms of CC BY.


Tanner M.,Swiss Tropical and Public Health Institute | Tanner M.,University of Basel | Greenwood B.,London School of Hygiene and Tropical Medicine | Whitty C.J.M.,London School of Hygiene and Tropical Medicine | And 16 more authors.
BMC Medicine | Year: 2015

Although global efforts in the past decade have halved the number of deaths due to malaria, there are still an estimated 219 million cases of malaria a year, causing more than half a million deaths. In this forum article, we asked experts working in malaria research and control to discuss the ways in which malaria might eventually be eradicated. Their collective views highlight the challenges and opportunities, and explain how multi-factorial and integrated processes could eventually make malaria eradication a reality. © 2015 Tanner et al.


Schindel D.E.,Smithsonian Institution | Bubela T.,University of Alberta | Rosenthal J.,Fogarty International Center | Castle D.,University of Victoria | And 24 more authors.
Nature Conservation | Year: 2015

The entry into force of the Nagoya Protocol of the Convention on Biological Diversity will lead to new legislation and regulations that could change international collaborative research in biology. This article suggests a new approach that researchers can use in negotiating international Access and Benefit Sharing agreements under the Protocol. Research on medicinal plants is used as a case study because it is a domain with many competing stakeholders involving non-commercial and commercial research, as well as national and international commercial markets. We propose a decision-based framework to aid all participants as they negotiate ABS agreements for non-commercial biodiversity research. Our proposed approach promotes transparency and builds trust, reflects the principles in the Convention on Biological Diversity, and respects and protects the interests of biodiversity rich developing countries. This approach is an alternative to often-used adversarial approaches. Copyright David E. Schindel et al.


Tambama P.,University of Zimbabwe | Abegaz B.,African Academy of science | Mukanganyama S.,University of Zimbabwe
BioMed Research International | Year: 2014

Cancer is a major public health burden in both developed and developing countries. The quinone moiety has been shown to possess antitumor activity and several cancer drugs in clinical use contain this entity. The effect of isofuranonaphthoquinone isolated from Bulbine frutescens on Jurkat T cells was determined. Cells were exposed to the isofuranonaphthoquinone (IFNQ) at different concentrations. Significant antiproliferative effects were observed which were comparable to that of the anticancer drug 1,3-bis(2-chloroethyl)-1- nitrosourea (BCNU). A combination of IFNQ with BCNU produced synergistic effects which were observed after 72 hrs. It was also observed that combining IFNQ with reduced glutathione abolished the anticancer activity of the compound. It is, therefore, proposed that the isofuranonaphthoquinone may exert part of its effect by producing reactive oxygen species resulting in death of the cells as the effects of this compound were antagonized by reduced glutathione. An investigation on the effects of isofuranonaphthoquinone on glutathione transferase (GST) activity and drug efflux pumps showed that this compound exhibited inhibitory effects on both the GST and the drug efflux pumping activities. Thus, the isofuranonaphthoquinone showed cytotoxicity, works through inhibition of some cellular mechanisms, and could present a potential source of lead compounds for anticancer drug development. © 2014 Penelope Tambama et al.


Tietjen I.,University of British Columbia | Tietjen I.,Simon Fraser University | Ntie-Kang F.,University of Buea | Mwimanzi P.,Simon Fraser University | And 13 more authors.
PLoS ONE | Year: 2015

The continued burden of HIV in resource-limited regions such as parts of sub-Saharan Africa, combined with adverse effects and potential risks of resistance to existing antiretroviral therapies, emphasize the need to identify new HIV inhibitors. Here we performed a virtual screen of molecules from the pan-African Natural Product Library, the largest collection of medicinal plant-derived pure compounds on the African continent. We identified eight molecules with structural similarity to reported interactors of Vpu, an HIV-1 accessory protein with reported ion channel activity. Using in vitro HIV-1 replication assays with a CD4+ T cell line and peripheral blood mononuclear cells, we confirmed antiviral activity and minimal cytotoxicity for two compounds, ixoratannin A-2 and boldine. Notably, ixoratannin A-2 retained inhibitory activity against recombinant HIV-1 strains encoding patient-derived mutations that confer resistance to protease, non-nucleoside reverse transcriptase, or integrase inhibitors. Moreover, ixoratannin A-2 was less effective at inhibiting replication of HIV-1 lacking Vpu, supporting this protein as a possible direct or indirect target. In contrast, boldine was less effective against a protease inhibitor-resistant HIV-1 strain. Both ixoratannin A-2 and boldine also inhibited in vitro replication of hepatitis C virus (HCV). However, BIT-225, a previously-reported Vpu inhibitor, demonstrated antiviral activity but also cytotoxicity in HIV-1 and HCV replication assays. Our work identifies pure compounds derived from African plants with potential novel activities against viruses that disproportionately afflict resourcelimited regions of the world. Copyright: © 2015 Tietjen et al.


Djoumessi A.V.B.,University of Yaounde I | Sandjo L.P.,University of Yaounde I | Sandjo L.P.,Johannes Gutenberg University Mainz | Liermann J.C.,Johannes Gutenberg University Mainz | And 8 more authors.
Tetrahedron | Year: 2012

Three new cyclopropanic oleanane triterpenoids and ten known compounds were obtained from Donella ubanguiensis using chromatographic methods. The structures were established on the basis of mass spectrometric and NMR data and by comparison with values reported in the literature. The structures of the new compounds were confirmed by X-ray crystallography. A part of the isolated compounds was evaluated for cytotoxic and antimicrobial activities. © 2012 Elsevier Ltd. All rights reserved.


Famuyiwa S.O.,University of Botswana | Sichilongo K.F.,University of Botswana | Yeboah S.O.,University of Botswana | Abegaz B.M.,African Academy of science
Phytochemistry Letters | Year: 2012

Eight homoisoflavonoids, two of which are new: 3-(4′-methoxybenzyl)- 5,6,7-trimethoxychroman-4-one (1); 3-(4′-methoxybenzyl)-5,7- dimethoxychroman-4-one (2); 3-(4′-methoxybenzyl)-7-hydroxy-5,6- dimethoxychroman-4-one (3); 3-(4′-methoxybenzyl)-6-hydroxy-5,7- dimethoxychroman-4-one (4); 3-(3′-hydroxy-4′-methoxybenzyl)-5,7- dihydroxy-6-methoxychroman-4-one (5); 3-(3′-hydroxy-4′- methoxybenzyl)-5,7-dihydroxychroman-4-one (6); 3-(4′-hydroxybenzylidene)- 5,7-dihydroxy-6-methoxychroman-4-one (7) and 3-(4′-hydroxybenzylidene)-5, 7-dihydroxychroman-4-one (8), were isolated from the yellow Inter-bulb deposits from Scilla nervosa. The structures of these compounds were elucidated and characterized by 1D- and 2D-NMR and mass spectrometry. The structures of the known compounds were compared to those ones in literature. © 2012 Phytochemical Society of Europe.


Awoussong P.K.,University of Yaounde I | Awoussong P.K.,University of Medicine and Pharmacy, Cluj-Napoca | Zaharia V.,University of Medicine and Pharmacy, Cluj-Napoca | Ngameni B.,University of Yaounde I | And 5 more authors.
Medicinal Chemistry Research | Year: 2015

Chalcones and their derivatives have been shown to have potent anticancer activity. A series of aldehydes A 1-4 and thiazolic chalcones C 1-20 were synthesized and evaluated for their in vitro cytotoxic activity against three human cancer cell lines. In addition, this work led to the synthesis of 12 new thiazolic chalcones using a base-catalyzed Claisen-Schmidt condensation reaction. Compounds C 10 and C 12 were found to be the most promising biologically active samples with IC50 values below or around 10 μM on both DU-145 and THP-1 cancer cell lines. © 2014 Springer Science+Business Media New York.


PubMed | University of Douala, Rockefeller University, Simon Fraser University, University of Buea and 4 more.
Type: Journal Article | Journal: PloS one | Year: 2015

The continued burden of HIV in resource-limited regions such as parts of sub-Saharan Africa, combined with adverse effects and potential risks of resistance to existing antiretroviral therapies, emphasize the need to identify new HIV inhibitors. Here we performed a virtual screen of molecules from the pan-African Natural Product Library, the largest collection of medicinal plant-derived pure compounds on the African continent. We identified eight molecules with structural similarity to reported interactors of Vpu, an HIV-1 accessory protein with reported ion channel activity. Using in vitro HIV-1 replication assays with a CD4+ T cell line and peripheral blood mononuclear cells, we confirmed antiviral activity and minimal cytotoxicity for two compounds, ixoratannin A-2 and boldine. Notably, ixoratannin A-2 retained inhibitory activity against recombinant HIV-1 strains encoding patient-derived mutations that confer resistance to protease, non-nucleoside reverse transcriptase, or integrase inhibitors. Moreover, ixoratannin A-2 was less effective at inhibiting replication of HIV-1 lacking Vpu, supporting this protein as a possible direct or indirect target. In contrast, boldine was less effective against a protease inhibitor-resistant HIV-1 strain. Both ixoratannin A-2 and boldine also inhibited in vitro replication of hepatitis C virus (HCV). However, BIT-225, a previously-reported Vpu inhibitor, demonstrated antiviral activity but also cytotoxicity in HIV-1 and HCV replication assays. Our work identifies pure compounds derived from African plants with potential novel activities against viruses that disproportionately afflict resource-limited regions of the world.

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