IN VITRO BEHAVIOUR OF PLASMODIUM FALCIPARUM STRAINS BY ALKALOIDS AND TANNINS EXTRACTED FROM ROOT OF MITRAGYNA INERMIS, A MEDICINAL PLANT

Objective: Mitragyna inermis (Willd.) O. Ktze is a plant belonging to the Rubiaceae family. It is used in West Africa by traditional healers for treatment of accesses febrile generally bound to access malaria, but also to treat several other pathologies. We have collected a medicinal plant, Mitragyna inermis root, currently used for malaria treatment in Burkina-Faso. Methods: Alkaloids and Tannins were extracted by using conventional methods and antimalarial activities were tested. Results: After extracted Alkaloids and Tannins, the in vitro culture of Plasmodium falciparum strain isolated from infected patients showed that the alkaloids extracts presented an excellent antiplasmodial activity on P. falciparum strain (IC50 = 2.36 and 2.56 µg/ml respectively) after 24 and 48h of incubation at 37 °C. On the other hand, the tannins extract no presented antiplasmodial activity (IC50>100 µg/ml) but presented an important maturity of P. falciparum strains, letting foretell a possible use of the polyphenolic compounds by P. falciparum as a source of cellular carbon and energy. Conclusion: These results although exploratory are of fundamental importance for the research in biochemistry and medicine for find new antimalarial prototypes

IN VITRO BEHAVIOUR OF PLASMODIUM FALCIPARUM STRAINS BY ALKALOIDS AND TANNINS EXTRACTED FROM ROOT OF MITRAGYNA INERMIS, A MEDICINAL PLANT

Mitragyna inermis (Willd.) O. Ktze, is a plant belonging to the Rubiaceae family. It is used in West Africa by traditional healers for treatment of accesses febrile generally bound to access malaria, but also to treat several other pathologies. We have collected a medicinal plant, Mitragyna inermis root, currently used for malaria treatment in Burkina-Faso. After extracted Alkaloids and Tannins, the in vitro culture of Plasmodium falciparum strain isolated from infected patients showed that the alkaloids extracts presented an excellent antiplasmodial activity on P. falciparum strain (IC50 = 2.36 and 2.56 µg/ml respectively) after 24 and 48h of incubation at 37 °C. On the other hand, the tannins extracts no presented antiplasmodial activity (IC50>100 µg/ml) but presented an important maturity of P. falciparum strains, letting foretell a possible use of the polyphenolic compounds by P. falciparum as a source of cellular carbon and energy. These results although exploratory are of a fundamental importance for the research in biochemistry and medicine for find new antimalarial prototypes.Keywords: Mitragyna inermis, Malaria, Roots, Tannins, Alkaloids, Plasmodium falciparum

O-glycosylation in plant and mammal cells: the use of chemical inhibitors to understand the biosynthesis and function of O-glycosylated proteins

Glycosylation is the most common posttranslational modification of proteins and consists of the addition of sugar moiety to proteins. The resulting glycosylated proteins are often secreted to the extracellular compartment or integrated into different cell organelles. This modification was identified in plant as well as in mammalian cells.  A number of plant and mammal proteins are either N- or O-glycosylated. This review focuses on O-glycosylation which refers to linkage of a glycan to hydroxyl group of serine, threonine or proline residues. O-glycosylation can be altered by the action of chemical inhibitors. For instance, 3,4-dehydro-L-proline, ethyl 3,4-dehydroxy benzoate and a,a-dipyridyl inhibit the activity of prolyl4-hydroxylase, a key enzyme for plant O-glycosylation. In addition, a small molecule inhibitor designated 1-68A inhibits the polypeptide N-acetylgalactosaminyltransferases of mammalian cells. The aim of this review is to summarize the role and mechanism of action of these inhibitors of O-glycosylation and their impact on cell development in plants and mammals

Alterations in Peripheral Blood B Cell Subsets and Dynamics of B Cell Responses during Human Schistosomiasis

Antibody responses are thought to play an important role in control of Schistosoma infections, yet little is known about the phenotype and function of B cells in human schistosomiasis. We set out to characterize B cell subsets and B cell responses to B cell receptor and Toll-like receptor 9 stimulation in Gabonese schoolchildren with Schistosoma haematobium infection. Frequencies of memory B cell (MBC) subsets were increased, whereas naive B cell frequencies were reduced in the schistosome-infected group. At the functional level, isolated B cells from schistosome-infected children showed higher expression of the activation marker CD23 upon stimulation, but lower proliferation and TNF-α production. Importantly, 6-months after 3 rounds of praziquantel treatment, frequencies of naive B cells were increased, MBC frequencies were decreased and with the exception of TNF-α production, B cell responsiveness was restored to what was seen in uninfected children. These data show that S. haematobium infection leads to significant changes in the B cell compartment, both at the phenotypic and functional level

Longitudinal estimation of Plasmodium falciparum prevalence in relation to malaria prevention measures in six sub-Saharan African countries.

BACKGROUND: Plasmodium falciparum prevalence (PfPR) is a widely used metric for assessing malaria transmission intensity. This study was carried out concurrently with the RTS,S/AS01 candidate malaria vaccine Phase III trial and estimated PfPR over ≤ 4 standardized cross-sectional surveys. METHODS: This epidemiology study (NCT01190202) was conducted in 8 sites from 6 countries (Burkina Faso, Gabon, Ghana, Kenya, Malawi, and Tanzania), between March 2011 and December 2013. Participants were enrolled in a 2:1:1 ratio according to age category: 6 months-4 years, 5-19 years, and ≥ 20 years, respectively, per year and per centre. All sites carried out surveys 1-3 while survey 4 was conducted only in 3 sites. Surveys were usually performed during the peak malaria parasite transmission season, in one home visit, when medical history and malaria risk factors/prevention measures were collected, and a blood sample taken for rapid diagnostic test, microscopy, and haemoglobin measurement. PfPR was estimated by site and age category. RESULTS: Overall, 6401 (survey 1), 6411 (survey 2), 6400 (survey 3), and 2399 (survey 4) individuals were included in the analyses. In the 6 months-4 years age group, the lowest prevalence (assessed using microscopy) was observed in 2 Tanzanian centres (4.6% for Korogwe and 9.95% for Bagamoyo) and Lambaréné, Gabon (6.0%), while the highest PfPR was recorded for Nanoro, Burkina Faso (52.5%). PfPR significantly decreased over the 3 years in Agogo (Ghana), Kombewa (Kenya), Lilongwe (Malawi), and Bagamoyo (Tanzania), and a trend for increased PfPR was observed over the 4 surveys for Kintampo, Ghana. Over the 4 surveys, for all sites, PfPR was predominantly higher in the 5-19 years group than in the other age categories. Occurrence of fever and anaemia was associated with high P. falciparum parasitaemia. Univariate analyses showed a significant association of anti-malarial treatment in 4 surveys (odds ratios [ORs]: 0.52, 0.52, 0.68, 0.41) and bed net use in 2 surveys (ORs: 0.63, 0.68, 1.03, 1.78) with lower risk of malaria infection. CONCLUSION: Local PfPR differed substantially between sites and age groups. In children 6 months-4 years old, a significant decrease in prevalence over the 3 years was observed in 4 out of the 8 study sites. Trial registration Clinical Trials.gov identifier: NCT01190202:NCT. GSK Study ID numbers: 114001

Induction of Plasmodium falciparum-Specific CD4+ T Cells and Memory B Cells in Gabonese Children Vaccinated with RTS,S/AS01E and RTS,S/AS02D

The recombinant circumsporozoite protein (CS) based vaccine, RTS,S, confers protection against Plasmodium falciparum infection in controlled challenge trials and in field studies. The RTS,S recombinant antigen has been formulated with two adjuvant systems, AS01 and AS02, which have both been shown to induce strong specific antibody responses and CD4 T cell responses in adults. As infants and young children are particularly susceptible to malaria infection and constitute the main target population for a malaria vaccine, we have evaluated the induction of adaptive immune responses in young children living in malaria endemic regions following vaccination with RTS,S/AS01(E) and RTS,S/AS02(D). Our data show that a CS-specific memory B cell response is induced one month after the second and third vaccine dose and that CS-specific antibodies and memory B cells persist up to 12 months after the last vaccine injection. Both formulations also induced low but significant amounts of CS-specific IL-2(+) CD4(+) T cells one month after the second and third vaccine dose, upon short-term in vitro stimulation of whole blood cells with peptides covering the entire CS derived sequence in RTS,S. These results provide evidence that both RTS,S/AS01(E) and RTS,S/AS02(D) induced adaptive immune responses including antibodies, circulating memory B cells and CD4(+) T cells directed against P. falciparum CS protein.ClinicalTrials.gov NCT00307021

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

Chemical compositions and anti-termite activities of essential oils from Gabonese Canarium schweinfurthii Engl, Dacryodes buettneri Engl and Aucoumea klaineana Pierre wood resins

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