**1. Introduction**

Malaria remains an important public health problem in several countries of tropical and subtropical regions of the world. In 2019, the disease caused an estimated 229 million clinical cases and around 409,000 deaths worldwide [1]. Five *Plasmodium* species are more frequently associated with human infection: Plasmodium *falciparum*, *Plasmodium vivax*, *Plasmodium malariae*, *Plasmodium ovale,* and *Plasmodium knowlesi*. The last species was recently related in a zoonotic transmission in Asia [2]. Although, cases from an outbreak in the Atlantic Forest

of Rio de Janeiro state, initially diagnosed as *P. vivax* infection, were in fact caused by *Plasmodium simium*, a neotropical primate parasite [3], other simian malaria parasites, morphologically, indistinguishable from *P. vivax*, the *Plasmodium cynomolgi*, have also been shown to have the potential of zoonotic transmission to humans through the bites of infected mosquitoes under natural and experimental conditions [4, 5]. Among the natural human *Plasmodium* species causing malaria in humans, *P. vivax* is the most widely distributed and prevalent outside of Africa [6], producing more than 80 million cases per year in these regions. Once considered clinically mild when compared with *P. falciparum* infection, *P. vivax* malaria causes debilitating effects that affect social and economic indices of the endemic regions and has been associated with the occurrence of severe cases around the world.

The circumsporozoite protein (CSP) of the infective sporozoite of all *Plasmodium* species can be evidenced in the process of maturation and salivary invasion in the vector as well as in human liver cells [7, 8]. Although it has been a major target in the development of recombinant malaria vaccines, this approach had to be re-evaluated because of the discovery of sequence variation in the repetitive sequence of its central portion gene [9, 10]. All CSPs present a central repeat region (CRR) and two conserved domains RI (region I - located in the amino terminal) and RII (region II – located in the carboxyl terminal). Sequence analyses of the *P. vivax* CRR CSP showed two repeats GDRA(A/D)GQPA or ANGA(G/D) (N/D)QPG belonging to one of the nonapeptide repeat units named VK210 or VK247, respectively [11, 12]. Lately, the *P. viv*ax-like was named by Qari et al. [10] to describe an 11-mer repeat sequence, APGANQ(E/G)GGAA containing variant, distinct from the two previously described, isolated from an infected individual in Papua New Guinea (**Figure 1**, [10, 13]). However, phylogenetic analyses of the SSU RNAr and Cyt B markers positioned both *P. vivax* CS genotypes in the same clade after revealing high similarity and diversity equal to zero between VK210 and *P. vivax*-like [14].

Finally, a high frequency of IgG antibodies against the N- and C-terminal regions of the *P. vivax* CSP was detected in comparison to the immune response to the VK210- and VK247-repetitive regions. Such difference was even more pronounced in *P. vivax*-like variant-caused infection cases. So, it appears that differences among the *P. vivax* CS variants are restricted to the central repeated region of the protein, mostly generated by nucleotide variation, with important serological consequences. These are information of great importance since such genetic diversity can be the product of intra-specific biological signatures, with major implications for the *P. vivax* CSP malaria vaccine trials [14].

### **Figure 1.**

*Schematic representation of the circumsporozoite protein (CSP) of* P. vivax*, comprising the central repeat region (CRR) flanked by the N- and C-terminal domains, including the conserved regions I and II. The CRR can have three forms denoted VK210, VK247, and* P. vivax*-like.*

*Circumsporozoite Protein from* Plasmodium vivax *and Its Relationship to Human Malaria DOI: http://dx.doi.org/10.5772/intechopen.102529*
