Analysis of pan-African Centres of excellence in health innovation highlights opportunities and challenges for local innovation and financing in the continent.

A pool of 38 pan-African Centres of Excellence (CoEs) in health innovation has been selected and recognized by the African Network for Drugs and Diagnostics Innovation (ANDI), through a competitive criteria based process. The process identified a number of opportunities and challenges for health R&D and innovation in the continent: i) it provides a direct evidence for the existence of innovation capability that can be leveraged to fill specific gaps in the continent; ii) it revealed a research and financing pattern that is largely fragmented and uncoordinated, and iii) it highlights the most frequent funders of health research in the continent. The CoEs are envisioned as an innovative network of public and private institutions with a critical mass of expertise and resources to support projects and a variety of activities for capacity building and scientific exchange, including hosting fellows, trainees, scientists on sabbaticals and exchange with other African and non-African institutions.

Traditional medicines as a mechanism for driving research innovation in Africa.

The outcomes from recent high profile deliberations concerning African health research and economic development all point towards the need for a mechanism to support health innovation on the continent. The mission of the African Network for Drugs and Diagnostics Innovation (ANDI), is to promote and sustain African-led health product innovation to address African public health needs through the assembly of research networks, and building of capacity to support human and economic development. ANDI is widely viewed as the vehicle to implementing some of these recommendations. There is tremendous opportunity for Africa, to leverage the expertise in natural products and traditional medicines in support of this objective to kick-start innovation. This report highlights key recommendations that have emerged through expert forums convened by ANDI on the challenges, opportunities and prospects for investing in this important area of research.

Antimalarial pyrido[1,2-a]benzimidazoles.

A novel class of antimalarial pyrido[1,2-a]benzimidazoles were synthesized and evaluated for antiplasmodial activity and cytotoxicity following hits identified from screening commercially available compound collections. The most active of these, TDR86919 (4c), showed improved in vitro activity vs the drug-resistant K1 strain of Plasmodium falciparum relative to chloroquine (IC(50) = 0.047 µM v 0.17 µM); potency was retained against a range of drug-sensitive and drug-resistant strains, with negligible cytotoxicity against the mammalian (L-6) cell line (selectivity index of >600). 4c and several close analogues (as HCl or mesylate salts) showed significant efficacy in P. berghei infected mice following both intraperitoneal (ip) and oral (po) administration, with >90% inhibition of parasitemia, accompanied by an increase in the mean survival time (MSD). The pyrido[1,2-a]benzimidazoles appeared to be relatively slow acting in vivo compared to chloroquine, and metabolic stability of the alkylamino side chain was identified as a key issue in influencing in vivo activity.

Integrated dataset of screening hits against multiple neglected disease pathogens.

New chemical entities are desperately needed that overcome the limitations of existing drugs for neglected diseases. Screening a diverse library of 10,000 drug-like compounds against 7 neglected disease pathogens resulted in an integrated dataset of 744 hits. We discuss the prioritization of these hits for each pathogen and the strong correlation observed between compounds active against more than two pathogens and mammalian cell toxicity. Our work suggests that the efficiency of early drug discovery for neglected diseases can be enhanced through a collaborative, multi-pathogen approach.

Schistosomes: challenges in compound screening.

Major progress in studying the biology of schistosomes had been achieved since the late 1960s with the successful laboratory cultivation of the parasite's life cycle stages in the vertebrate (in vivo animal models) and snail hosts. This was followed by establishment of in vitro culture techniques for cultivation of the different life cycle stages to understand the mechanisms regulating the parasite's growth, development, transformation, pathogenicity and survival, with prospects to develop and identify relevant candidate diagnostic, immunological and chemotherapeutic targets. Chemotherapeutic measures have been the mainstay in the control of schistosomiasis. The use of praziquantel, a relatively safe and orally administered drug, in targeted or mass treatment programmes had significantly reduced the prevalence of schistosomiasis in disease-endemic countries. However, with only one drug of choice for treatment, parasite resistance remains a major concern. Thus, new drug discovery against schistosomes cannot be overemphasised. Undoubtedly, this will require an integrated system that includes not only rational chemical synthesis and lead optimisation, but also appropriate drug screening strategies. This paper reviews the present state of in vitro and in vivo drug screening strategies against schistosomes. It also highlights the best practices for compound screening in the TDR-designated compound screening centres and details some of the challenges involved in in vitro and in vivo compound screening.

Challenges in drug discovery for novel antifilarials.

Control programmes are at present focused on the elimination of onchocerciasis and lymphatic filariasis as public health problems in countries where they are endemic. The availability of effective drugs used in combination (diethylcarbamazine, albendazole and ivermectin) has paved the way for the implementation of Mass Drug Administration (MDA) campaigns. Considerable progress in the implementation of MDA programmes had led to significant reductions in transmission and morbidity. However, new drugs are needed to overcome the threat of resistance to existing microfilaricides as well as to identify new macrofilaricides. This paper discusses the existing screening tools available for antifilarial drug discovery and efforts towards optimising their use through the Helminth Drug Initiative.