EDITORIAL: WOMEN IN MALARIA RESEARCH

Alena Pance^1*Elena Gómez-Díaz²Sarah Reece³

• ¹School of Life and Medical Sciences, University of Hertfordshire, Hatfield, United Kingdom
• ²Instituto de Parasitologia y Biomedicina Lopez-Neyra, Granada, Spain
• ³The University of Edinburgh, Edinburgh, United Kingdom

Over the last century of intense research, much progress has been achieved, in terms of understanding parasite, vector and host biology, host-parasite interactions, transmission and population dynamics. The advent of next-generation sequencing, single cell and stem cell technologies, gene editing and imaging together with advances in computational biology have significantly transformed the field and opened multiple new areas of study. Together with this technological advancement, the last decade has seen more attention been paid to the hidden parasite variability in endemic areas, and with this, the necessity of having more representative reference genomes and more realistic models for laboratory experiments. Enormous data bases of field parasite isolates and vectors from all over the world now exist (MalariaGen) that provide a detailed picture of the parasite and vector striking biology and diversity. This also allowed important advances in understanding the disease itself, including mechanisms of infection, intra-host adaptation, and transmission dynamics, and with this more comprehensive knowledge about malaria epidemiology and control. Finally, with efforts reaching a plateau in malaria control and the continuous emergence and spread of resistance to antimalarials and insecticides all over the world, research and development of next-generation drugs and vaccines and a better understanding of immunity to malaria, are hot priority areas.Involvement of women in all these aspects of malaria research has steadily increased in number and importance in the last decades. The aim of this special collection is to showcase the varied work of female scientists in all areas of malaria research.One of the areas that has exploded, in terms of applying all the portfolio of novel technologies, is the vector. New knowledge about their basic biology, ecology and adaptation potential is becoming more and more critical in the context of climate change and globalisation. Aligned with this need is the number of articles addressing it within this topic. On one hand, a better understanding of regulatory mechanisms of gene expression, such as alternative splicing, and the identification of candidate genes and regulatory sequences that could offer novel strategies for vector control (Diaz-Terenti et al). Of critical importance is the development of the parasite within the vector and Oke et al reveal that that oocyst development is highly adapted to the nutritional state of the mosquito (Oke et al). Furthermore, models integrating parasite stages within the host and the vector, link gametocyte density in the host to transmission potential after vector passage, allowing more realistic estimations of parasite transmission potential (Hoi et al). Diversity of the circulating parasites is greatly determined by the rate of transmission and variation in the mosquito population shapes malaria transmission, seasonal persistence and geographical range. Not only genetic diversity of the major species of mosquitos harbouring the parasite but also the number of species capable of transmitting the disease contribute to the persistence and spread of malaria. Hence tools targeting specific genes or gene drive strategies need to take into account genetically divergent species to be effective (St. Laurent). The evaluation of control measures for the determination of the evolution of resistance among mosquito populations relies on the capture of field mosquitos at different stages. A mathematical model evaluated the value of adult-capture as a tool to monitor insecticide resistance, showing that this approach is effective and relatively easy to apply (Homldahl et al).Most clinical repercussions of malaria infection are due to the erythrocytic stages of the parasite. Novel technologies such as optical tweezers provide detailed insight into the infection of erythrocytes, showing membrane rigidification as the parasite grows and also of surrounding uninfected erythrocytes in the culture. Interestingly, widely used antimalarials increase rigidity of infected erythrocytes but only when the parasite strains are sensitive to the particular drug (Dorta et al). While mathematical models of blood infection dynamics are very useful, measuring erythrocyte and reticulocyte densities revealed that novel formulations are needed to reflect them more accurately (Peters, et al). Comparison of Poisson with non-parametric methods to estimate multiplicity of infection concluded that the model to use will depend on the transmission characteristics, such that over-dispersed distribution is well represented by non-parametric methods while if not highly over-dispersed, a Poisson model is appropriate (Kayanula and Schneider). The development of the parasite in the blood is highly synchronous, which is characteristic of the Plasmodium genus and important for disease progression and control. An analysis using a model that takes into account population dynamics and infection kinetics to quantify synchrony showed that strains and environments can be compared in this way, informing evolutionary drivers and the role of synchrony in disease (Greischar, et al).The tools available to control malaria include diagnostic methods to detect the disease, targeting the infection in patients with drug combinations as well as preventing infection mainly through vaccine development and vector control. All these tools are constantly challenged by genetic diversity of parasites and vectors as well as drug resistance and environmental factors. Indeed, evaluation of Rapid Diagnostic Test (RDT) accuracy in Uganda showed a high proportion (approximately 20%) of false positive results. This level of sensitivity risks inappropriate treatment and underdiagnosis of other illnesses and highlights the need for constant improving and updating of diagnostic tools (Mortazavi, et al). One of the novel options to assess drug resistance, ion torrent deep sequencing, can effectively assess the haplotypes of the most important drug resistance genes and even detect changes in allele frequency throughout the infection. This could be a straight forward technique to monitor drug efficacy (Kale at al). Even comparison of reference genomes of P. vivax focusing on drug resistance genes revealed allelic variations between them that should be taken into account when establishing detection and vaccine development strategies for this species of parasite (Tamang, et al).The strategy that has proven most effective to control and reduce transmission of malaria has been the distribution of insecticide-impregnated bed nets. However, the efficacy of bed nets has been declining due to resistance. A measure to counter this is a next-generation bed-nets with pyrethroid second chemistry. Assessment of three WHO-recommended classes of these dual-active nets showed that they outperform the traditional ones. However, variability in outcomes across Africa points to the need of a regional approach for the best control strategy (Böhmert, et al). Similarly, the local approach to control malaria was also highlighted by Skinner, et al who use statistical modelling to analyse the effect of local climate and spatial variations in factors such as land use, entomological features, temperature and rainfall on malaria transmission. Finally, all measures to control the disease have to include local communities to understand the specific needs and requirements for any strategy to be effective, as described by the 'one health' approach (Knudson Ospina, et al).This special collection is only a small sample of the amazing work of women in the efforts to bring malaria under control. It demonstrates the extensive involvement of women scientists in innovative and important work across the breadth of malaria research unravelling unknowns and discovering new approaches. The hope is that this small insight will serve as inspiration to women to continue their efforts and encourage men and academic institutions to support, value, celebrate and disseminate their contributions.