This morning was full of exciting science on the malaria parasite and its interaction with human and mosquito hosts. A common message from the presenters was the dynamic nature of parasite populations. Today’s parasites are adapting to evolutionary pressure and will not be the same in the future. As countries reach elimination, tools and strategies need to adapt as well.
In his talk on interventions that block parasite transmission to the mosquito, Rhoel Dinglasan (University of Florida, USA) highlighted the complex yet largely unknown interactions between parasite ligands and mosquito receptors in the midgut. He shared ongoing work from his lab, e.g. testing parthenin as a “chemical condom” that inhibits male gametogenesis and other research to cure infected but not yet infectious mosquitoes. A promising target for vaccine development is the mosquito ligand (AnAPN1). Results show that antibodies to AnAPN1 can block its interaction with the parasite and data from mouse models show that it can be delivered as nano/microparticles. Could this be the basis for a future pan-malaria transmission blocking vaccine?
Sara Volkman (Harvard T.H. Chan School of Public Health, USA) gave an overview on how genetics, and in particular molecular barcoding of parasites, can contribute to surveillance-response in malaria elimination. Data from Senegal show that genetic parasite signatures reflect transmission intensity and patterns. As intensity of transmission declines, the complexity of infection shifts from polygenomic to clonal, and parasite relatedness increases. Genetic tools termed “identity by decent” may help to differentiate local from imported parasites and detect which infections are contributing to transmission.
Alfred Cortes Closas (ISGlobal, Spain) explained how parasites of the same genetic background can increase their diversity by activating or silencing some genes (a strategy called bet-hedging). He showed data indicating that parasite adaptation occurs at the non-genetic level, and that these stochastic epigenetic changes could have an impact on drug resistance, transmission or virulence. Other work from Alfred’s lab shows that a transcription factor is critical for parasites to transform into sexual stage gametocytes and that some drugs can stimulate this sexual conversion.
Abdoulaye Djimdé (University of Science, Techniques and Technologies, Mali) presented recent data from the Plasmodium Diversity Network Africa (PDNA) network that screens for parasite diversity and markers of resistance to drugs. Initial work has started by looking at the K13 gene and a study performed in Mali indicates that artemisinin monotherapy (tested in the research protocol) remains effective but heterogeneity in parasite clearance time requires further investigation.
Didier Menard (Institut Pasteur, Cambodia) presented approaches to identify molecular signatures for monitoring antimalarial drug resistance in Cambodia. Six artemisinin resistance-associated mutations in the P. falciparum K13 gene have been described. Two main foci in Asia were identified and data show that one of the six mutations in the K13 gene (C580Y) has become fixed. On the other hand, K13 mutations in Africa are rare and not associated with drug resistance and other world regions seem to be free of resistance-related Asian alleles for the moment.
Moses R. Kamya opened the afternoon session, which turned its attention to surveillance strategies at the programme level. Moses is a senior Professor at Makerere University College of Health Sciences, Uganda where Keystone attendees had enjoyed a site visit earlier this week. Researchers in bacteriology, mycobacteriology, molecular biology, immunology and translational research explained their projects and many collaborations with African and international institutions. The hope is that the interactions between Makerere researchers and Keystone attendees may be the start of collaborations to come. In his presentation, Moses shared a series of studies performed by the ICEMR (The East African International Centre of Excellence on Malaria Research) to evaluate the impact of the scale up of the core interventions in Uganda. Great strides have been made, but pyrethroid resistance remains a challenge.
Abdisalan Mohamed Noor (WHO Global Malaria Programme, Switzerland) presented a realistic and sobering picture on the current state of surveillance in many African countries, where the greatest burden of malaria exists. He emphasized that action is what distinguishes surveillance from monitoring. Problems (such as too many indicators, registers and reports) and recommendations (such as strengthening human resources) were discussed. “It may be boring and difficult, but it is the single most important thing we have to do to move to the next step, and the only one for which we have the tools”, he said. In the words of D. A. Henderson, “surveillance is the neurological system of public health”.
Marcel Tanner (Swiss Tropical and Public Health Institute, Switzerland) closed the meeting with a keynote lecture on the impact of travel and migration on the risk of malaria reintroduction. Echoing Noor, he stressed the need for strong and responsive surveillance systems which utilize minimal essential information and collect data in near real time to enable rapid responses. The challenge is not only increasing the effectiveness of the core interventions, but achieving “equity effectiveness” so that interventions reach all vulnerable groups. This is especially pertinent at during this time of social fragmentation.
In their concluding remarks, the scientific organizers highlighted the excellent quality of the questions from the young scientists, the added value and rich discussion by hosting the meeting in Uganda and announced their goal for a future Keystone Symposia on malaria elimination and eradication in Asia.
Correction: Yesterday's 22 February 2017 blog incorrectly stated that Stephen Hoffman's sporozoite vaccine led to promising "immune responses", and should have read "the vaccine has promising protective efficacy".
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.