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Promising new candidates for the malaria tool kit

February 24, 2017 - 12:01 -- MESA Alliance

Keystone Symposia malaria meeting in Kampala - Day 4

Wednesday, 22 February 2017

Today’s sessions focused on tools for malaria elimination, including promising vaccine and drug candidates, and novel vector control.

Marcus Lacerda (Fiocruz, Tropical Medicine Foundation Dr. Heitor Vieira Dourado, Brazil) shared study findings and perspectives from clinical medicine in the Amazon.  For P. vivax elimination, the Achilles heel is G6PD deficiency (G6PDd), since it limits the use of the 8-aminoquinoline primaquine, which targets the hypnozoite.  He commented that investing in diagnostic testing for G6PDd would prevent haemolysis in patients and would also be cost-saving for the health system.  Notwithstanding the G6PDd challenge, the antimalarial candidate tafenoquine has recently completed a Phase III trial and if results are positive could be recommended and registered in 2018.

Kelly Chibale (University of Cape Town, South Africa) presented exciting work from the H3D drug discovery centre in collaboration with Medicines for Malaria Venture (MMV).  They have discovered that an aminopyrazine (UCT943) has potent activity across the different stages of the life cycle of both P. vivax and P. falciparum.  Their data show that it is efficacious in vitro and in humanized mouse models of malaria, selectively targets the PI4K kinase, has good pharmacokinetic and safety data, and is soluble.

Stephen Hoffman (Sanaria, USA) offered a sobering reminder that there are more cases of malaria today than there were polio cases when the polio eradication campaign began. Innovation and tenacity in the field of malaria elimination are essential. He presented data from an iterative set of studies on the the sporozoite-based vaccine candidate, which led to optimising immune responses through dose escalation.  The work is progressing in partnership with many international researchers and stakeholders, particularly those in endemic countries. 

With five different parasite species, genetic diversity, and highly differentiated stages of the life cycle, developing vaccines against the malaria parasite is not for the faint hearted.  Louis Schofield (James Cook University, Australia) presented data on a new target antigen that is highly conserved across all stages of the parasite life cycle: GPI (glycophosphatidylinositol).  Data show that GPI induces high titers of antibodies and prevents severe disease in animal models, reduces blood stage replication and blocks transmission to mosquitoes, possibly by interfering with parasite mobility.  

Itziar Ubillos (ISGlobal, Spain) gave a short talk on the characterization of antibody responses to the parasitic antigen circumsporozoite protein in children and infants in Sub-Saharan Africa participating in the Phase III trial for the RTS,S/AS01E malaria vaccine. Her work will allow a better understanding of the mechanisms of protection induced by the vaccine.

Umberto D’Alessandro (Medical Research Council Unit, The Gambia) shared work on a pilot study the characterization of residual transmission after one round of MDA with dihydro-artemisinin-piperaquine in several villages.  The evidence suggests that there are parasite flows from the east to the west of the country, and that local transmission can be rapidly re-established after the MDA intervention period.

Didier Leroy (MMV, Switzerland) shared key points about testing for resistance as part of the development of the next-generation of antimalarials. He underlined the need to integrate new mutants from the field in laboratory parasite test panels, to test compounds against field isolates as well as known resistant parasites, and to generate artemisinin resistance in vivo to mimic the situation in the field.

The afternoon session focused on vector control, the cornerstone of malaria prevention.  Charles Wondji (Liverpool School of Tropical Medicine, UK) highlighted key questions in insecticide resistance: what is the resistance profile and intensity; what are the molecular drivers; and what is the actual impact on malaria transmission?  Analysis of the gene expression indicates that different resistance mechanisms have arisen in different regions.  The need for new active ingredients on LLINs is crucial to prevent multiple resistance mechanisms developing in the same mosquito populations.

John Lucas (Sumitomo Chemical Company, Japan and UK) underlined that currently there are limited options in the insecticide toolbox, and emphasized the critical role of insecticide resistance management starting from the development process right through to implementation in the field, so that we can maintain susceptibility of the vector to these hugely effective vector control tools

Krijn Paaijmans (ISGlobal, Spain) presented surveillance results in Mozambique indicating that vector composition, densities and insecticide resistance differ between and within villages. He underlined the need to go back to the drawing board and rethink entomological surveillance by reassessing when and where vectors and humans interact. He emphasized the responsibility of entomologists to obtain good quality data and ensuring that the maximum number of people are protected for every dollar spent on vector control.

Closing the session on vector control, Sheila Ogoma Barasa (US Army Medical Research Directorate, Kenya) presented early data on novel vector control tools, which aim to protect people in public and outdoor spaces where IRS and LLINs do not prevent mosquitoes from biting.   Shelia and colleagues have been testing transfluthrin-treated mats for sitting or sleeping on and transfluthrin-treated decorations to hang inside homes, bars or restaurants.  Data suggest that they can provide long-term and long-distance protection against mosquitoes.  However, further testing is needed and resistance to the pyrethroid class of insecticide needs to be addressed.

We are sending daily posts from Kampala, Uganda, during the week-long Keystone Symposia meeting, 'Malaria: From Innovation to Eradication', organized in collaboration with MESA. Additional funding was given by The Bill & Melinda Gates Foundation and the US NIH/NAIAD. This blog was posted simultaneously on ISGlobal's blog, the Malaria World website, and the MESA website.