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Ahmadu Bello University, established in 1962, is a federal university in Zaria, Nigeria whose mission is to...

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Malaria kills almost half a million people each year, mostly young children in sub-Saharan Africa. Decreased sensitivity of malaria parasite field isolates to artemisinin, the most recent antimalarial to be used in the field, is emerging, and it is of crucial importance to maintain an active research to develop new interventions. People living in malaria endemic areas develop naturally acquired immunity (NAI) after repeated exposure to malaria. However, the mechanism of NAI is not well understood. The fellowship aims to improve the understanding of how naturally acquired immunity works to protect against clinical malaria. For that purpose, the host scientists Darren Creek and Christian Doerig at Monash University, Australia, and the fellow Abdirahman Abdi from the Kenya Medical Research Institute have conducted controlled human malaria infection on Kenyan adults who had had varying levels of prior exposure to natural malaria infection.

Rintis Noviyanti from the Eijkman Institute for Molecular Biology (EIMB), Indonesia, and the host scientists at the Walter and Eliza Hall of Medical Research (WEHI), Australia, Diana Hansen and Alan Cowman, employed advanced technology and research methods, including cytometry by time-of-flight (CyTOF), and fluorescence-activated cell sorting (FACS), a derivative of flow cytometry that adds an exceptional degree of functionality for sorting cells. They used these technologies and methods, together with data mining and analysis, to identify biological markers present in individuals with natural immunity to Malaria.

This fellowship of Indra Wibowo from the Institut Teknologi Bandung, Indonesia, with Wai-Hong Tham from the Walter and Eliza Hall Institute of Medical Research (WEHI), Australia, aimed to identify functional blocking antibodies that inhibit red blood cell binding and ligand-receptor interactions present in individuals in a region of high Malaria transmission in Indonesia. PfRh5 is one of the leading vaccine candidates against blood stage P. falciparum and PfRh4 governs the major invasion pathway independent of glycophorin-mediated entry.

Institute Pasteur Madagascar (IPM) is working with cohorts of EPTB (Extrapulmonary tuberculosis) patients in collaboration with local clinicians to better diagnose EPTB and accelerate diagnosis. IPM is gathering clinical, bacteriological as well immunological data and samples from these patients (clinical extrapulamonary Mtb (mycobacterium tuberculosis) strains, blood samples and other fluids), aiming to increase the Institute immunological investigation capacities in order to propose new options with new tools to diagnose EPTB with an integrated approach (host, pathogen, immune response). At IPM, the human host capacities need to be upgraded to meet with the international standards and increase the capacity to understand the host-pathogen interaction and build tools to fight against EPTB from this interaction. In this project, Paulo Ranaivomanana from IPM and Anna Coussens from WEHI work together to strengthen IPM capacities in assessing the immunological correlates that may be associated with extrapulmonary dissemination of Mtb. Understanding the determinants of Mtb dissemination can be useful to build diagnostic tools for EPTB.

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Assets

A synthetic vaccine is available for testing against P. falciparum malaria. Control of malarial disease has been achieved on a limited basis in certain parts of the world; however, no vaccine presently exists that can provide protective immunity. This synthetic vaccine contains a peptide which induces the activation of cytotoxic T cells that specifically recognize and kill cells infected with malaria sporozoites.
A transmission blocking vaccine developed against malaria contains a recombinant virus, which encodes a unique portion of the sexual stage surface antigen of Plasmodium falciparum (referred to as Pfs25), or the Pfs25 protein purified from infected host cells. Mice inoculated with the recombinant virus developed antibodies capable of blocking transmission of the virus. None of the monoclonal antibodies known to block transmission recognize the reduced Pfs25 antigen. This vaccine, which induces high, long-lasting titers at low cost, can be useful for controlling malaria.
Malaria therapeutic Release of hemoglobin into the blood is a central pathophysiologic event contributing to morbidity and mortality in chronic and acute hemolytic anemias and severe malaria. These toxicities arise from hemoglobin-related scavenging of nitric oxide, a blood vessel vasodilator, and peroxidative chain reactions that lead to damage of the surrounding tissues. Animal models have demonstrated both an attenuation of the hypertensive response due to nitric oxide scavenging and a prevention of peroxidative toxicity. Compartmentalization of hemoglobin, rather than short-lived nitric oxide-based drugs, may represent a new therapeutic paradigm in countering the pathophysiological side effects associated with free hemoglobin. This technology identifies haptoglobin and haptoglobin mimetics as potential therapeutics for high blood pressure and intravascular toxicity due to release of hemoglobin from red blood cells. It provides a novel process in which free hemoglobin is compartmentalized within the haptoglobin molecule. Therapeutic proof-of-principle has been demonstrated for this technology in dog and guinea pig models.
This invention relates to the identification of functional domains of Plasmodium proteins which play a role in erythrocyte binding and invasion. The inventors have identified the erythrocyte binding domains of the sialic acid binding protein (SABP) of P. falciparum and the Duffy antigen binding protein (DABP) of P. vivax. The erythrocyte binding domains can be used as vaccines to induce immune responses which block erythrocyte binding and invasion by P. falciparum and P. vivax merozoites.
Anti-plasmodium composition and methods of use Compositions that inhibit the binding of Plasmodium falciparum to erythrocytes are provided. More particularly, antibodies specific for Plasmodium falciparum binding proteins and blocking peptides that prevent the binding of Plasmodium falciparum are included in the present invention. The methods provided utilize the antibody and peptide compositions provided herein and include methods for the diagnosis, prevention, and treatment of Plasmodium falciparum diseases such as malaria as well as methods for the detection of Plasmodium falciparum in biological samples and culture media.
Compounds inhibiting the growth of a virulent strain (H37Rv) of Mycobacterium tuberculosis (Mtb) were discovered by testing 214,519 thousand pure, small molecules with drug like propertiesin a biosafety level 3 hiboratory. Discovery of novel pharmacophores inhibiting the growth of mycobacterium tuberculosis employed screening of a 214,519 pure, small molecules library that is part of the NIH Road Map Molecular Libraries Probe Centers Network MLSCN program. 610 compounds inhibited M tuberculosis growth by 90 per cent or greater and of these compounds, approximately 591 compounds were non-toxic to tissue culture cells at 10 J.lM. Twenty-two major chemical clusters covering approximately 243 active compounds were identified by structure similarity analysis along with 26 compounds in 6 minor clusters. Four hundred sixty-four active compounds did not form clusters. The potency ranged from <0.20 J.lM to I0 ~IM with 78 compounds having IC90s of>0.20 J.lM.