Introduction

Malaria is a disease that has affected the human population since ancient times. Today, it remains one of the infectious diseases with the highest morbidity and mortality rates, with more than one million people dying every year from this disease worldwide [1]. It is produced by different species of a protozoan parasite of the Plasmodium genus distributed especially in the tropical and subtropical areas of the planet. The most widespread species are P. falciparum and P. vivax, responsible for more than 95% of cases. Four other species affect humans: P. malariae, P. ovale curtisi, P. ovale wallikeri, and P. knowlesi. Of all of them, P. falciparum is the species that produces the most severe form of the disease and mainly affects the African continent where the child population is the most susceptible along with pregnant women. However, cases of severe malaria caused by P. vivax [2] are currently being reported. This species extends to areas of the Asian continent, Oceania, and Central and South America. In some regions, there are frequent cases where both species coexist [3].

The parasite is transmitted by female mosquitoes belonging to the genus Anopheles that inoculate the sporozoites when they bite humans; these through the peripheral circulation reach the liver cells where they multiply and transform into merozoites that pass into the bloodstream to infect the red blood cells inside which they will develop and multiply until the breakage of the blood cell releasing new merozoites that will invade new red blood cells (schizogonic cycle). After several erythrocyte cycles, some merozoites become the sexual stages of the parasite (male and female gametocytes) which are the forms that will pass to the mosquito when it bites a sick individual. Inside the mosquito, the zygote will form and after migration through the mosquito midgut, the sporozoites (sporogonic cycle) will develop that are transferred to the salivary glands closing the cycle. In P. vivax and P. ovale, the parasite can take a latent or dormant form; they are the hypnozoites that can become active after a period of time, transforming into merozoites that would invade the red blood cells triggering the disease.

Unlike other pathogenic organisms such as bacteria or viruses, parasites have a complex eukaryotic cell organization with complex life cycles as well as enormous antigenic variability and mechanisms capable of evading the host immune response, all of which make it difficult to obtain vaccines. It is a fact that there are currently no vaccines against parasitic protozoa such as Leishmania, Trypanosoma, or Plasmodium despite infecting millions of people worldwide. In the case of malaria, the emergence of resistance to the drugs used to treat it, as well as resistance to insecticides to combat Anopheles mosquitoes or the emergence of zoonotic species, has put research into obtaining a vaccine as the necessary tool to prevent transmission and eliminate the disease at the forefront [4].

The search for a vaccine against malaria is nothing new. In the twentieth century, it was thought that it was possible to get a vaccine when in the 1970s, volunteers inoculated with irradiated P. falciparum and P. vivax sporozoites developed full immunity (sterilizing) to the bites of infected mosquitoes in more than 90% of cases. However, the duration was moderate [5]. It has also been found that people living in malaria-endemic areas progressively acquire partial immunity that protects them from clinical disease, especially severe malaria and death [6, 7] as well as a decrease in parasitemia levels to almost undetectable levels [8]. Passive immunity was also achieved by transferring immunoglobulins obtained from the “immune” serum African individuals to Thai children experiencing recrudescence of malaria infection [9]. All this evidence suggested that a vaccine against malaria was possible and there are many different studies in this field. However, despite the many efforts made, there is still no effective vaccine to provide at least 75% protection. The fact that there are no suitable experimental models for human Plasmodium species makes research extremely difficult and slows down, and although large number of candidate vaccines is currently being evaluated, few are in the clinical phase.

The selection of antigens to be included in a vaccine is not easy, because, although research on the parasite proteome has provided numerous potential targets, few are selected as vaccine candidates [10, 11].

The first strategy chosen to design possible vaccines was to select antigenic targets from the different stages of the life cycle capable of inducing humoral and/or cellular response, and so pre-erythrocytic stage, blood stage, and transmission-blocking vaccines have been developed. The former tries to prevent infection by preventing the invasion to hepatocytes or by eliminating those that have already become infected, preventing any of the symptoms of the disease. Erythrocyte vaccines prevent the development of the disease by acting on circulating merozoites and preventing them from invading red blood cells. Therefore, they do not prevent the disease, although they would decrease its severity. The latter are known as altruistic vaccines because they do not prevent infection or disease in the person receiving them. These act on the sexual forms, both in the human and in the mosquito, preventing the transmission of the disease. Pre-erythrocyte vaccines and transmission-blocking vaccines have the advantage of acting on cycle bottlenecks, where the number of parasites is lower, and therefore the probability of success is higher. The primary goal of the first vaccines developed against malaria was to reduce morbidity and mortality in children living in highly endemic countries. However, in the face of the changing disease landscape, the new challenge is to eliminate and eradicate the disease, and it is essential to develop vaccines that are capable of reducing and preventing the transmission of the parasite. In this new scenario, the malERA (Malaria Eradication Research Agenda) Consultative Group on Vaccines introduces a new concept of vaccines that interrupt malaria transmission (VIMT) to replace the term transmission-blocking vaccines (TBVs) [12]. This new term includes not only vaccines directed against the vector, but also highly effective pre-erythrocytic or erythrocytic stage vaccines, and vaccines targeting parasite antigens of sexual and mosquito stages of the infection. The aim of this new strategy is to prevent infection. In 2013, malERA also recognized the need to include P. vivax in studies of antimalarial vaccines, as there are now regions where this species is even more untreatable than P. falciparum.

Advances in the knowledge of the Plasmodium genome and in molecular biology techniques have made it possible to better understand the vector-human and host-parasite interactions, contributing to the design of new vaccines [13]. Subunit vaccines contain part or complete antigens and recombinant DNA technology has facilitated the development of these types of vaccines in different expression systems. The first vaccines designed as recombinant protein subunit vaccines generally induce a poor cellular response. The newest generation of subunit vaccines are DNA based. DNA and recombinant viral vaccines can induce high levels of cellular response although the humoral response is low.

Subunit vaccines against pre-erythrocyte phases have demonstrated high protection against malaria infection. A truly effective vaccine should prevent the invasion to hepatocytes by inducing high antibody titers against sporozoites that would prevent their entry, and high T cell responses against the infected hepatocytes. This would prevent the emergence of blood-borne parasites, including sexual forms, and thus prevent transmission. Two strategies have been used for the development of pre-erythrocyte vaccines: selecting an appropriate antigen and using complete sporozoites. In the first case, one of the antigens selected was the surface antigen of the circumsporozoite, CS, the largest surface protein of the sporozoite, essential for its development and expressed the intracellular hepatic stages. This protein contains three regions: an N-terminal domain, which binds to the hepatocyte; a central region; and a C-terminal domain. Although other immunogenic sporozoite proteins related to hepatocyte mobility and invasion have been identified [14], none have induced an immunogenic response comparable to CSP. Thus, the vaccine RTS,S/AS01 was designed, developed by GlaxoSmithKline as Mosquirix, which contains much of the primary sequence of P. falciparum CSP fused to a hepatitis B surface antigen to form a virus-like particle and these were mixed with the adjuvant AS02 [15]. This was the first first-generation vaccine to complete phase III of the clinical trial and is the first and only vaccine so far to show a protective effect against malaria in young children in clinical trials. However, the results are worse than expected, with only partial (36%) and short-term effectiveness [16,17,18]. It is important to note that clinical trials began in 2002 and ended in 2014 [19], so it is likely that the sequence used is based on a laboratory strain isolated decades ago that does not represent the protein of the parasites currently circulating in endemic areas [20]. It may be necessary, in the design of new vaccines, to make modifications in the design of the antigen because recent research by Tan et al. [21] and Kisalu et al. [22] have shown that most antibodies to P. falciparum circumsporozoite protein (PfCSP) bind to the central region of the protein, while most protective antibodies also bind to unidentified epitope, not included in the RTS,S/AS01 vaccine. These epitopes are related to hepatocyte invasion, so this region of PfCSP should be included in a future vaccine [18]. Sack et al. [20] consider that for next-generation subunit vaccine, variants representing the most prevalent genotypes should be included, as well as adding new antigens other than PfCSP, as antibodies obtained from individuals immunized with sporozoite vaccines and protected from CHMI recognize a large number of non-PfCSP antigens.

Currently, there are not many non-PfCSP recombinant PE vaccine candidates in clinical trials. A protein component of vaccines is the cell-traversal protein for ookinetes and sporozoites (CelTOS), which is localized to micronemes that are organelles for parasite invasive motility. It was the first protein identified as a potential target by Mining Genomic and Gene Expression Databases [23]. The human vaccine is in the clinical phase [17]. Another selected protein is thrombospondin-related adhesive protein (TRAP), essential for sporozoite motility and host cell invasion. Against this protein, individuals in endemic areas have high levels of antibodies, anti-PFTRAP. Different types of vaccines have been developed with this protein without good results. Bauza et al. [24] suggest that a combination of CSP and TRAP subunit vaccines could enhance protection against malaria.

The viral-vectored vaccines have now gained importance as they have shown very good results in stimulating high T cell responses. One strategy employed to improve the cellular immune response of protein-based subunit vaccines has been to use viral-vectored vaccines [24,25,26] using chimpanzee adenoviral vector (ChAd63) or modified vaccinia strain Ankara (MVA) in heterologous prime-boost immunization regimes [27, 28]. Some candidates are in the experimental phase with encouraging results [29,30,31].

Studies, both in humans and animals, show the possibility of achieving sterile immunity by vaccination [5, 32]. McCarthy and Clyde [32] have led to the development of vaccines with complete sporozoites (PfSPZ) attenuated by different mechanisms. These types of vaccines induce a broad cellular and humoral response. Several candidate vaccines are currently being investigated, including PfSPZ-attenuated sporozoites by irradiation [33], vaccines in which the sporozoites are fully infectious and are attenuated by the joint administration of the antimalarial drug PfSPZ-CVac [34], and vaccines with attenuated sporozoite by the knockout gene PfSP-GA1 [35]. There are 43 research groups in 15 countries, collaborating in the advancement of this type of vaccine manufactured by Sanaria and that have been shown to induce a broad cellular and humoral response [31, 36].

The erythrocyte or blood-stage highly effective vaccines are also included in the new concept of ITVL because by lowering the density of asexual forms below the threshold required for infectious gametocyte production, they block the transmission from the parasite to the vector. Pre-erythrocyte vaccines rely on the reduction of parasitemia and clinical symptoms in children with severe malaria who were given serum from hyperimmune adults [9, 37]. The proteins expressed on the surface of the merozoite, the blood form of the parasite, represent the first targets due to repeated exposure in the host immune system [11]. Some of these were correlated with immune protection in endemic regions or identified by screening expression libraries with hyperimmune sera. The proteins present on the surface of parasitized red blood cells also represent potential targets, and they are associated with natural immunity to malaria, but their high diversity is a major drawback to vaccine design. The blood-state vaccines have been deprioritized in favor of targeting pre-erythrocytic and mosquito stage parasites. The main obstacles to its development are the antigenic polymorphism of both the merozoites and the surface proteins of infected red blood cells, the redundancy in the merozoite invasion pathways [38], and the difficulties in producing natively folded proteins. The main blood-stage vaccine candidate currently is PfRh5, a merozoite protein, essential for red blood cell invasion [39,40,41]. A first generation of this vaccine is being tested in clinical trials in Oxford and Tanzania [42]. Another vaccine being developed is the AMA1 (apical membrane antigen 1)-RON2L (rhoptry neck protein 2) complex, which is targeted against the invasion of merozoites. Both form a complex essential for merozoite invasion during the blood stage of infection [43]. Attempts at vaccines with AMA1 alone have failed [44], while forming a complex with RON2L improves the immunogenicity of some preserved AMA1 epitopes. Another antigen showing preclinical promise is schizont egress antigen-1 (SEA-1) [45]. SEA-1 is a parasite antigen expressed in schizont-infected red blood cells (RBCs) that is essential for schizont rupture in the blood state. Antibodies to PfSEA-1 are associated with a reduction in the incidence of severe malaria. It is not known whether these antibodies would also block the exit of the liver schizont, but it should be investigated as this would mean that a single vaccine would block an essential process in multiple states [46].

Finally, malaria transmission can also be interrupted with vaccine to disrupt parasitic infection of the host mosquito, also identified as a transmission-blocking vaccine. There are currently two vaccine candidates. The first of these is directed against the post-fertilization antigen, Pfs25, expressed in zygotes and oocytes. The second is directed against the preferred antigen, Pfs230, a protein expressed in gametocytes. In ongoing trials, these have been combined with an exoprotein (EPA) to increase their immunogenicity. Currently, the Pfs25-EPA/alhydrogel conjugate vaccine is in phase 1 clinical trials in the USA and Africa [47]. The recombinant Pfs230D1M protein is also being investigated and is considered a promising option for a blockade of transmission vaccine [48].

Another potential target is Pfs47, a protein that makes parasites “invisible” to mosquitoes’ immune systems [49]. Recent research suggests that Pfs47 acts as a “lock and key” because if P. falciparum has Pfs47 haplotype compatible for a given anopheline mosquito, this is sufficient for the parasite to evade mosquito immunity [50]. Therefore, Pfs47 can be considered as a vaccine candidate.

The next generations of vaccines must combine several potential targets from different stages in the Plasmodium life cycle to achieve greater effectiveness, multi-state, and multicomponent vaccines. In this regard, knowledge and use of genomic resources is essential, as has been demonstrated by various trials, such as those that accelerate genome-wide functional approaches in mice with the aim of accurately reproducing certain aspects of the pathogenesis of human infectious diseases [51].

Materials and methods

In this analysis, the search query [TITLE-ABS-KEY (malaria AND vaccine AND gene)] in the Elsevier Scopus database was performed. As a result, 2254 documents met the selection parameters. It must be considered that using alternative search parameters, the results obtained can be different. It should also be borne in mind that Elsevier Scopus is a dynamic database that can include, delete, or move a document from 1 year to another, depending on its own parameters. This dynamic nature of the database may result in minimal changes in the result of a search carried out at two different times but does not alter the meaning of the analysis and the conclusions that can be drawn from it.

In the analysis of the keywords, these were processed by grouping those that had the same meaning, but a different spelling, as is the case, for example, of Plasmodium falciparum and P. falciparum. In addition, those whose consideration did not contribute anything to the analysis, such as, Article, were discarded.

The aspects that have been studied are number of publications per year, distribution of publications by country and by institutions, main authors, and keywords. The set of articles obtained in the main search is represented by a network with nodes and links between them. Nodes are their keywords and their importance is represented by the size of the node and its centrality in the network. The size of the connection between two nodes represents the number of relationships between the two keywords, so the larger the relationship between those two keywords. If it is desired to know around which topics the articles are grouped, those parts of the network that are more interconnected with each other, it is necessary to use a community detection algorithm. Finally, community detection algorithm is applied to the network of the main query to group the global research trends to the search criteria. As less strongly related elements are associated with this nucleus, the peripheral elements are structured. In addition, community detection was carried out using a VOSviewer software tool, which allows the generation of graphs. In these graphs, the collaborations between countries and keywords, which are represented by nodes, are displayed.

The results obtained were processed using OpenRefine (http://openrefine.org/), an open source tool. OpenRefine “is a standalone desktop application initially developed by Google for data cleansing and transformation to other formats.” This methodology facilitates the massive analysis of disorganized data that would otherwise be very difficult to understand, given the large size of the database used. This methodology has been used successfully in other bibliometric studies [52]. The results obtained by OpenRefine were tabulated in spreadsheets.

Results

Evolution of scientific output and subject area

Figure 1 shows the evolution of the number of publications on vaccines and genes in malaria worldwide around 1979, the year in which the first article on this subject was published, and 2017, the last full year for which data are available. The results show a remarkable growth in the number of publications, from an average of 1.8 publications per year in the first 5 years to an average of 120 publications in the last 5 years. But there is no linear growth with a constant increase in the number of articles published each year, but a typical pattern of sawtooth growth can be observed in the graph, with relative minimums and maximums appearing in a high number. In any case, there is no doubt about the significant increase in the number of publications over the period, with an average growth of 3.5 documents per year. Throughout these almost 40 years, 2254 documents have been published with this theme. Figure 1 also shows the number of cites received for articles published each year—in green bars. In this case, it can be observed that the evolution of the growth in the number of citations is proportional to the growth in the number of articles, until 2008. After this one, there is no time perspective big enough to keep it that way. There is a year that breaks the rule. It is the year 2002. This year’s articles have received, in total, more than 8000 cites. This is due to the fact that in that year, two of the five articles in this series that have received the most citations were published. Of these, the article in which the sequencing of the P. falciparum genome was published stands out [53], with more than 2700 cites.

Fig. 1
figure 1

Trend of the number of publications from the years 1977 to 2017 and the cites received for articles published each year

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Subject area analysis establishes that the three areas in which most articles are classified are immunology and microbiology, medicine, and biochemistry, genetics, and molecular biology, with 55, 51, and 40%, respectively, of the publications classified in these. But if the data are analyzed according to the evolution in the classification by subject area in each of the four decades into which this study can be divided, it can be seen that these values have not been constant over time (Fig. 2). This fact is especially notable in the area of medicine. While in the 1980s, only 36% of articles were classified in this area and in the last decade, the value has increased to more than 60%, demonstrating the great interest that the development of a vaccine against malaria generates in the field of human health.

Fig. 2
figure 2

Evolution of the main subject areas in which publications about vaccines and genes in malaria are classified

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Publication distribution by countries and institutions

Eleven institutions have been found to have published at least 50 publications on vaccines and genes in malaria. The National Institute of Allergy and Infectious Diseases and the National Institutes of Health with 163 and 158 publications, respectively, stand out from the rest. Among these are five North American institutions; four European—three British and one French; one Australian; and one Latin American, from Brazil. These data are consistent with the results of the analysis by country, not by institution. In this instance, the country with the most articles published on this subject is the USA, with 933, followed by the UK, with 363. At a considerable distance are the rest of countries such as Australia, with 196 publications or France, with 162. The remaining countries with at least 100 publications on vaccines and genes in malaria are India, Japan, Germany, Brazil, Holland, Switzerland, and the Netherlands.

Figure 3a shows a world map. In this, each country’s scientific production of vaccines and genes in malaria is highlighted in color. It is observed that the countries with the most publications in this field are the USA and the UK. At a second level are countries with incidence in this disease, such as Brazil or India, but also France, Germany, Japan, or Australia. And on a third level of importance, there are countries like Colombia, China, and Kenya. If this analysis is carried out with the publications on vaccines and genes with respect to the total number of malaria publications and these are represented in %, Fig. 3b is obtained. It is now clear that some countries have focused their scientific efforts in this field, like the Dominican Republic, where 40% of its malaria publications are on this subject. In this new ranking, there appear countries that in absolute value did not have great scientific production; however, in these relative terms, they appear at the same level as Colombia. These are Honduras, Nicaragua, or Papua New Guinea. On the other hand, it is striking that Australia is still in this ranking and is one of the countries with a large scientific production in this domain, which shows that they also invest a great effort in this field within the malaria studies.

Fig. 3
figure 3

World map of publications of vaccines and genes related to malaria

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Figure 4a shows a distribution in communities of the countries that have published at least 25 articles. The 24 countries that appear in the distribution are grouped into five clusters. The first of the clusters, highlighted in red in figure, is made up of Italy, Colombia, Papua New Guinea, Spain, Switzerland, and Australia, as the central country. The second of the clusters, highlighted in green, is made up of Brazil, China, Japan, South Korea, Thailand and the USA, as the central country. Denmark, Kenya, the Netherlands, Sweden, Tanzania, and the UK, as the central country, can be found in the third cluster, highlighted in blue in figure. The remaining are two smaller clusters, with three countries each; Belgium, Canada, and India on the one hand, highlighted in yellow, and France, Iran, and Germany on the other, highlighted in violet. In addition, the relationship between two countries is represented by the thickness of the joint line of two nodes.

Fig. 4
figure 4

Scientific communities and their associations in publications on vaccines and genes in malaria. Each cluster is represented by a color. a Communities of countries. b Communities of researchers

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Main authors

Twenty-one authors have been found to have published at least 25 publications on vaccines and genes in malaria. Most of these (8 out of 21) are from the USA. In addition, there are three authors from the UK, three from Australia, and three from Japan. There are also four other countries with one author among the main authors: Colombia, Brazil, Thailand, and the Netherlands. Of all these authors, SL Hoffman and AVS Hill stand out from the rest, with 57 and 53 articles, respectively. The first of them participated in the sequencing of the P. falciparum genome, and also stood out for its genomic studies of the malaria parasite and DNA vaccines, while the second one focuses its research, above all, on the study of the immunogenicity of some vaccines.

Figure 4b shows a graph of the relationships established by the main authors with at least 25 published articles on vaccines and genes in malaria. From this type of representation, it is possible to deduce the links that each author establishes with other researchers. This analysis facilitates the establishment of relationships such as those of Americans SL Hoffman with DL Doolan or M Sedegah, who have co-published 54 articles related to the immunology of malaria, or those of the British AVS Hill and SC Gilbert, who have co-published 131 papers, also related to the immune response to malaria. But it is even more remarkable that the only author who does not appear in the graph is the Latin American, MA Patarroyo. This is because it lacks links with the other main authors. This should not be interpreted as a meaning that he does not investigate. In fact, according to the Scopus database, this author has published almost 200 articles to date, which have received more than 1800 citations. The only thing that can be deduced is that their collaborations are developed in a different line to the object of this study.

Table 1 shows the 11 institutions with, at least, 50 publications on vaccines and genes in malaria. Of these, two institutions stand out: The National Institute of Allergy and Infectious Diseases, and the National Institutes of Health, with 163 and 158 publications, respectively. These institutions are also the ones with the highest H-index and their articles have the highest number of cites. If the attention is paid to the average number of cites received per article, it can be observed that the Naval Medical Research Center has a very high number, 92.2 compared to the average value of these 11 institutions, which is 54.4 cites per article. This is because the researchers at this center were responsible for some of the most cited articles [53, 54].

Table 1 Main institutions that publish on vaccines and genes related to malaria
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Keywords analysis

To carry out the analysis of the keywords, the terms that do not contribute anything to the analysis have been discarded. For example, “article,” “journal,” or “review.” In addition, different keywords with the same meaning, such as “Plasmodium falciparum” and “P. falciparum,” were considered as a single keyword. The results shown that the 20 keywords that appear most frequently in articles on vaccines and genes in malaria ranged from 1625 for “Nonhuman” to 423 for “Immune Response.” The other terms that appear in this list are Human, Animals, Malaria, Plasmodium Falciparum, Malaria Vaccine, Parasite Antigen, Controlled Study, Protozoan Proteins, DNA Sequence, Unclassified Drug, Antigens Protozoan, Female, Genetics, Mouse, Immunology, Gene Expression, Animal Experiment, and Amino Acid Sequence.

Finally, the temporal evolution of the publications around the four Plasmodium species that appear most often in the keywords of the analyzed articles has been studied (Fig. 5). These four species are P. falciparum and P. vivax, which cause malaria in humans, and P. berghei and P. yoelii, which infect rodents and are used as model organisms and in vaccine studies. As can be seen, although P. falciparum has always occupied a prominent place in this ranking, since 2002, coinciding with the publication of the sequencing of its genome, publications on this parasite have soared. This analysis was also carried out considering the publications of the three countries with the greatest scientific production, the USA, the UK, and Australia, and the result was similar, indicating that the observed trend is independent of the country considered.

Fig. 5
figure 5

Time evolution of the number of publications for the most studied Plasmodium species

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Discussion

An analysis of the evolution in the number of publications on vaccines and genes in malaria since 1979, when the first article on this subject was published, to 2017, the last year for which complete data are available, shows an increase that is not constant, but which does mark a clear trend. This trend is consistent with the great interest that malaria provokes in the international scientific community and with the growing awareness that the fight against the disease and its eradication must be aimed at a definitive vaccine. An important milestone was achieved in 2002: Sequencing of the complete genome of P. falciparum, the human malaria parasite that causes the most deaths each year. This was clearly reflected in the number of publications. There was an increase of 37.8% over the previous year worldwide.

In this analysis, in addition to the trend in the number of publications, other variables have been studied. Thus, 70% of the publications are research articles, 20% are reviews, and the remaining 10% are conference paper, note, editorial, etc., or that most of these articles are published in journals in the areas of immunology and microbiology, or medicine. But, above all, special attention has been paid to studying which institutions, countries, or researchers play a fundamental role in the publication of articles on vaccines and genes in malaria.

Thus, it has been possible to establish a ranking led by the National Institute of Allergy and Infectious Diseases, the National Institutes of Health, and the Walter Reed Army Institute of Research, in the USA, and by the University of Oxford and the London School of Hygiene & Tropical Medicine, in the UK, with more than 500 documents published by all of them. Among the main authors, the American SL Hoffman and the British AVS Hill stand out from the rest. His research on immunology, on vaccine development, and on the study of resistance in severe malaria highlights the direction of global research on vaccines and genes in malaria.

In summary, it can be concluded that research on vaccines and genes in malaria is of great concern to the international scientific community. The number of publications on this subject has grown enormously in the last 40 years, highlighting the increase produced by the introduction of next-generation sequencing as a fundamental tool in the molecular study of malaria. This gives us an idea of the path that research in this area will take. The analysis of the genomes of P. falciparum and P. vivax to find a vaccine to help eradicate malaria has become essential, and all efforts are now focused on the development of bioinformatics tools to help process all the information generated. However, the overall objective of achieving the vaccine that will make it possible to eradicate malaria once and for all is only possible through cooperation and joint efforts, and not only at the level of scientific parallels or economic interests, but also at the political and institutional level. For this reason, it is essential to know the relationships established between the different research groups working on these lines, to join forces and to add up knowledge.