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India-EMBO Lecture Course: understanding malaria from molecular epidemiology, population genetics, and evolutionary perspectives

2023; Elsevier BV; Volume: 39; Issue: 5 Linguagem: Inglês

10.1016/j.pt.2023.02.010

1471-5007

Abhinav Sinha, Sonalika Kar, Nimita Deora, Manoswini Dash, Aparna Tiwari, Lokesh Kori, Kristan A. Schneider, Lisa Ranford‐Cartwright,

Mosquito-borne diseases and control

The India-EMBO Lecture Course was organized during November 2022, where 13 exemplary speakers shared their expertise in malaria molecular epidemiology, population genetics, and evolution in five thematic sessions. In addition, 50 enthusiastic participants worldwide introduced their research in oral and poster presentations. In this TrendsTalk, the conference organizers bring to you the highlights of these scientific sections as well as the networking and entertaining events afterwards. Abhinav Sinha Sonalika Kar Nimita Deora Manoswini Dash Aparna Tiwari Lokesh Kori Kristan Schneider Lisa Ranford-Cartwright To address the most urgent problems affecting malaria epidemiology, clinical pathogenesis, and therapeutics, the India-EMBO Lecture Course was uniquely conceived from three interconnected perspectives: molecular epidemiology, population genetics, and evolution. Thirteen stalwarts in these intersecting disciplines and 50 participants from all around the globe joined this event (Figure 1), which was run from 17–23 November 2022 at the Le Meridien hotel in Gurgaon, Delhi NCR, under the aegis of the ICMR-National Institute of Malaria Research, India. The course was custom-designed to suit a 7-day residential event where the speakers, participants, and organizers resided at one comfortable venue throughout the course. The course included five thematic sessions with lecture talks from invited experts. The participants were selected from 142 applications, eight of whom presented a 10-minute turbo talk, while the remaining 42 participants had the opportunity to present their research in one of the two poster sessions. Besides excellent deliberations, gender balance was promoted among speakers and participants. Mentoring of young talents was another cross-cutting priority. Throughout the course, interaction between young talents and senior faculty was proactively encouraged with specific activities. Below are the highlights from scientific sections and social events during the course. In this section, Ananias Escalante (Temple University, USA) set up the concept of understanding the dynamics of malaria from a molecular evolution perspective. Ananias laid out the interconnection between malaria population genetics, molecular epidemiology, and epidemiology with respect to how disease patterns are generated (through population genetics and molecular epidemiology) and how they relate to contemporary health events (through molecular epidemiology and epidemiology). The principles of population genetics and molecular evolution were explained in detail by Rasmus Nielsen (University of California Berkeley, USA) and Sudhir Kumar (Temple University, USA), respectively. Rasmus discussed selection and evolutionary forces in his lecture and explained the dynamics of the host–parasite interactions and evolutionary arms race. The technical facets of molecular phylogeny and its importance in comprehending molecular ancestry were the focus of Sudhir's lecture on the principles of molecular evolution and phylogenetics. He concentrated on the fundamentals of phylogenetics and molecular evolution and elaborated on the use of molecular phylogeny in estimating the origins of genes, evolutionary relationships of organisms, selective pressure, and genotype–phenotype connections. Maria A. Pacheco's (Temple University, USA) lecture elucidated the mode, rate, and diversification of the haemosporidian parasites over time, which laid the basis of the origin and radiation of the human malaria parasites. Maria concluded that the radiation of haemosporidian parasites is likely the result of community-level evolutionary processes between their vertebrate and invertebrate hosts. Talking on the evolution of human malaria vectors, Catherine Walton (University of Manchester, UK) highlighted the high biodiversity of Anopheles species in Southeast Asia, many of which are malaria vectors. Using a combination of phylogenetics, population genetics, and landscape genomics, she examined the factors that have facilitated the diversification and geographic spread of human malaria vectors. Julio Gallego-Delgado (City University of New York, USA) mentioned how extremely high child mortality rates have made malaria the strongest known selective pressure on the human genome and explained how the human renin–angiotensin system has been genetically adapted to protect from cerebral malaria in childhood but, at the same time, risks the development of hypertension in adulthood. Lucio Luzzatto (Muhimbili University of Health and Allied Sciences, Tanzania), in his talks on malaria and human genetic polymorphisms, exemplified how malaria has shaped the human genetic landscape. Lucio detailed the role and mechanisms of hemoglobin S (HbS) variants and glucose-6-phosphate dehydrogenase (G6PD) deficiency in providing protection from severe malaria in humans. In his second lecture on X-linked genes and human diseases, Lucio further elaborated how the severe anemia in malaria is differentially manifested in hemizygous G6PD-deficient boys and heterozygous G6PD-deficient girls. In a turbo talk, Anaswara Sugathan (Stockholm University, Sweden) showed how two sympatric ethnic groups of Africa are differentially susceptible due to their genetic and epigenetic makeup. Alyssa Barry (Deakin University, Australia) opened this section with discussion on malaria molecular genomic epidemiology and how it can be of help in malaria control and elimination. She explained the importance of assessing the genetic relatedness between malaria parasites in the understanding of molecular processes happening across populations. Alyssa further elaborated on the use of genetic distance between parasites and measures of estimating the genetic relatedness. She also compared the cost of targeted sequencing (molecular markers) and whole-genome sequencing as molecular tools. Marcelo U. Ferreira (Nova University of Lisbon, Portugal) presented the potential use of parasite population genetics/genomics in malaria surveillance: tracking the emergence and spread of drug resistance, hrp2 deletion and increased virulence, distinguishing local and imported cases, tracking epidemics, reconstructing transmission chains to identify targets for control, and assessing the impact of interventions. He mentioned the challenges of population genomic studies that include the choice of obtaining blood samples, processing the samples before sequencing, dealing with low parasite density/poor DNA quality, and analyzing low-coverage genome data. Kristan Schneider (Hochschule Mittweida University of Applied Sciences, Germany) deliberated on molecular data analysis of Plasmodium parasites in the context of transmission intensities and seasonal malaria and highlighted that the fundamental aim of molecular surveillance is to reconstruct unobservable information from observable patterns, which allow reconstruction of evolutionary processes and routes of transmission, and identify genes under selection. Kristan emphasized the importance of 'effective recombination' in generating genetic diversity when multiplicity of infection (MOI) is >1. He further elaborated how the increase in MOI is directly related to the intensity of transmission that generates more genetic variation. There are three turbo talks in this section. Irene Molina de la Fuente (Institute of Health Carlos III, Spain) presented the molecular epidemiology of malaria for public health strategies in malaria control in South Sudan. Jason Rosado (Insititut Pasteur, France) discussed the development of a novel PvAmpSeq assay with high resolution to distinguish between relapses, recrudescence, and reinfections. Tamar Grossman (Public Health Laboratories, Israel) explored an increasing rate of artemether-lumefantrine treatment failure in 15 Israeli Plasmodium falciparum-positive travellers returning from sub-Saharan Africa. Rasmus started this section and laid the foundation of important concepts in malaria population genetics and their correct implementation and implications for understanding the parasite genetic diversity, selection pressure, and drift. Rasmus also laid the basis of molecular phylogeny and measures to quantitate genetic diversity using different estimators. Rasmus concluded that malaria population genetic studies can aid traditional epidemiological surveillance in identifying imported malaria, intensity of transmission, and transmission networks. With real-world data from India, Aparup Das (ICMR-National Institute of Research in Tribal Health, India) talked on how population genetics studies informed the evolutionary epidemiology of malaria in India. Aparup employed both the P. falciparum and Plasmodium vivax models to elucidate the population structure, demography, and dispersion of drug-resistance markers in India. Kristan justified the use of mathematical and genetic models to understand the origin and spread of antimalarial resistance, particularly amidst a scarcity of reliable clinical and epidemiological data and substantial different transmission rates, treatment policies, vector, natural and host-acquired immunity across endemic areas. Kristan shared different models to explain the evolution and spread of drug resistance and hrp2 gene deletions in malaria parasites. Sudhir delivered an exhaustive talk on molecular phylogenetics and explained the development, purpose, and applications of the tool MEGA not only in malaria but in any phylogeny. He explained the fundamentals of phylogeny and the complex and intense algorithms behind it to generate the best-fit tree for accurately predicting the ancestry by bootstrapping and increasing sensitivity. Lisa Ranford-Cartwright (University of Glasgow, UK) talked about understanding the genetics of laboratory-developed experimental crosses between strains of malaria parasites and how this information may be applied to improve our understanding on the population genetics of natural populations. She reiterated the importance of effective recombination in the presence of more than one genotype in human and mosquito hosts in augmenting the genetic diversity. In a separate lecture, Lisa explained how quantitative trait locus (QTL) analysis in P. falciparum attempts to link phenotypes to genotypes from a genetic map. To supplement the lectures, a hands-on session led by Kristan using the software 'R' for molecular data analysis was held to allow the participants to work with the real data and to learn and resolve queries in a live session. This was followed by three turbo talks. Thomas Stabler (Swiss Tropical and Public Health Institute, Switzerland) discussed if the P. falciparum population on Bioko Island (BI), Equatorial Guinea, was distinct from those in nearby continental Africa. Theresia Njaube Metoh (University of Bamenda, Cameroon) discussed the genetic diversity of P. falciparum and genetic profile in children affected by uncomplicated malaria in Cameroon. Abhinay Ramprasad (Francis Crick Institute, UK) showed that inclusion of Plasmodium vinckei genomes provide new insights into the evolution of rodent malaria parasites and their multigene families. In this section, Catherine illustrated the use of R0 in malaria transmission and control by explaining the Ross–Macdonald two-host model. To reduce the R0 for malaria, one or more of the following should be reduced: number of mosquitoes, biting rate, mosquito lifespan, duration of infection in humans, and the transmission probabilities. S. Noushin Emami (Stockholm University, Sweden) explained how mosquitoes communicate with each other to locate their prey through chemosensory proteins that detect specific substances in the environment. By understanding the communication and feeding behavior of mosquitoes, novel vector-based strategies can be developed to control the spread of diseases they transmit. This lecture shed light on the complex biology of mosquitoes and provides valuable insights for the development of more effective control measures. Starting the section, Marcelo broadly covered the topics discussed during the course and further elaborated on the need to understand the Ross–Macdonald malaria model for achieving malaria elimination. He mentioned that, although the model is still valid, it misses variation, diversity, and heterogeneity in parasite, vector, and human population. He also stressed the need to understand the Pareto principle in malaria elimination – 20% of the hosts harbor 80% of the pathogen burden and are responsible for 80% of its transmission, the so-called 'super-spreaders'. Marcelo highlighted the crucial role of low-density Plasmodium infections in malaria elimination. He ended his talk with the importance of understanding the spatial heterogeneity and reactive-case detection in malaria control. Ananias talked about some of the fundamental principles when planning future research, particularly in the context of declining malaria cases. He highlighted the roles of valid hypothesis, sample size, evolutionary process under question, sampling, and statistical power when planning evolutionary genetic studies. Ananias stressed the use of a model-based hypothesis in contrast to a mere speculation that cannot be tested. He compared the use of evolutionary processes under investigation in population genetic studies with the importance of sampling in classical epidemiological studies. He also stressed the need of doing pilot studies and archiving samples during surveillance for genetic studies. Maria went on to discuss sample collection methods, different molecular methods for studying parasite genetic diversity, and what questions can be answered by looking at parasite genetic diversity. She concluded by summarizing the techniques and approaches commonly used to generate molecular information in the context of epidemiologic investigations. Noushin presented her achievements in vector control wherein she investigated the phagostimulant activity of a Plasmodium metabolite in various mosquito species. She also investigated the use of a toxic-plant-based artificial feeding solution as an effective and environmentally friendly tool for controlling vector populations. There were three participant-led and interactive panel discussions to address the underrated topics among the budding researchers. One panel discussed how to write the discussion section of a scientific publication and concluded that repeated practice is the key to expertise this skill. Another panel discussed the prospects after PhD or PostDoc (Figure 2A ). A very good point was raised by the panellists that one should have a plan B apart from the main plan. The third discussion focused on striking the right balance between work and life, and the panellists advised that if one takes his/her work as a passion, the question of balancing it with life will not even arise. Two poster sessions with drinks and light bites were organized to provide ample time and space for critical discussions and evaluation (Figure 2B). Prizes were distributed to appreciate participants' research work in the form of three prizes each for turbo talks and posters. First prizes, sponsored by the journal EMBO Molecular Medicine, in the form of a voucher for €100, were awarded to Abhinay Ramprasad and Elizabeth Riana Dwi Prasetyawati (Chulalongkorn University, Thailand). Second prizes of cash ₹5000 were bestowed on Anaswara Sugathan and Megan Michel (Max Planck Institute for Evolutionary Anthropology, Germany). Third prizes of cash ₹3000 were awarded to Thomas Stabler and Priya Agrohi (ICMR- National Institute of Malaria Research, India). In addition, a special prize of ₹1000 was won by Xiomara Gaitán (University of São Paulo, Brazil). To provide some light relief from scientific contents, two entertaining sessions, Gala Dinner and Delhi excursion, were embedded in the course. The dinner provided a great opportunity to meet the invited guest speakers and participants in a relaxed and informal atmosphere wherein all attendees were requested to wear traditional costumes to represent their national cultures and traditions, adding to the spectacle (Figure 2C). A local Delhi excursion was also organized, which included a grand Indian Rajasthani cuisine lunch and visits to various tourist attractions in Delhi. The participants agreed that the course offered a great setting for exchanging research ideas and establishing new contacts. A few valuable suggestions received from attendees included more hands-on sessions, directed panel discussions, and longer duration of poster sessions. The event's organizing committee would like to express their gratitude to all the speakers who took time from their busy schedules to make their deposit by the high-quality presentations and stimulating discussions for the fellow participants. The organizers and team are grateful to: the EMBO as the major financial supporter with additional support from Wellcome Trust India Alliance; Government of India through the department of biotechnology (Conference, Travel, Exhibition and Popular Lectures grant); the Company of Biologists Limited, Cambridge, UK (Scientific Meeting Grant); the British Society For Parasitology, UK; the Barcelona Institute for Global Health, Barcelona, Spain (ISGLobal); eLife Sciences Publications Ltd, Cambridge, UK; Tulip Diagnostics Pvt Ltd, India; Q-line biotech Pvt Ltd, India, Invitrogen BioServices, India; Lonza, India; DSS Takara Bio India Pvt. Ltd, India; GeneX India Bioscience Pvt. Ltd., India; Genetix Biotech Asia Pvt. Ltd., India; SPT Labtech, India; Azure Biosystems, India; Solution One life sciences India Pvt Ltd, India; Promega Corporation, India and Pragati biomedical, India. We are thankful to the Indian Council of Medical Research, and ICMR-National Institute of Malaria Research, New Delhi, for administrative approvals to conduct the event smoothly. We are grateful to the Ministry of External Affairs, Govt. of India and extend our warm thanks to the venue hotel Le Meridien, Gurugram. Viraj Chauhan Films, Mumbai, India captured still and video photography. The event was successfully managed on the ground by 24/7 support from the organizing team members and volunteers (Prem Singh Rajpoot; Tanvi Lakra; Priyanka Rathore; Princy Gautam; Shakeel Ahmed). We are also thankful to the vendors, transport facilitators and all ICMR-NIMR staff who supported the event.