**3. Life cycle**

**Asexual Phase (Human)** stage completed in humans after the invading of sporozoite to the liver which further infected other RBCs after parasitemia establishment. **Sexual Phase (Mosquito)** completed in the gut of mosquito [20]. When parasite bite infected humans, gametocytes occur in female and male form reach in their salivary gland and enter into the gut of the mosquito. The male and female gametes are fused in the gut of the mosquito to form zygotes [21]. After fertilization of gametes, ookinetes form which penetrates the gut epithelial cells and finally converts into an oocyst. The oocyst multiplies by asexual replication and produces sporozoites. Rupture of the mature oocyst releases the sporozoites into the hemocoel (body cavity) of the mosquito, from where they travel to the mosquito salivary glands [22]. When an infected mosquito has a blood meal, it injects saliva containing the parasite (sporozoites) into the human bloodstream, causing malaria infection in the new human host. Now the sporozoites travel through the circulatory system to the liver and invade hepatocytes, where the sporozoites multiply and grow through asexual replication known as exoerythrocytic schizogony. Each sporozoite develops into a schizont containing thousands of merozoites, which are released into the bloodstream. In the case of *P. vivax* and *P. ovale,* they live in a latent form in the liver-cell which can be dormant up to months or years. These hypnozoites relapse when a new primary infection reaches to liver cells [23]. The erythrocytic life cycle begins when free merozoites invade through erythrocytes. The erythrocytic cycle is responsible for all clinical manifestations of the disease. Merozoites invade erythrocytes by multiple receptor-ligands interactions within a few seconds. The early trophozoite is often called 'ring form' because of its morphology. Ring stage is developed into the trophozoite stage by metabolizing host cytoplasm and degradation of hemoglobin into globin and amino acids. The trophozoite is developed to schizont by multiple rounds of nuclear division without cytokinesis and produces 8–32 daughter merozoites [24, 25]. Mature merozoites came outside the red blood cell and released merozoites invade new RBCs and this cycle repeats. This blood stage cycle is responsible for the pathology related to malaria. Asexual stage converted into sexual stages i.e. male, female gametocyte [26, 27]. Which helps in the transmission of the infection to others through the female Anopheles mosquitoes, wherein they continue the sexual phase of the parasite's life cycle.
