a year. persistent liver stages allow relapse up to five years after elimination of red blood cell stages and clinical cure. liver stage the p. vivax sporozoite enters a hepatocyte and begins its exoerythrocytic schizogony stage. this is characterized by multiple rounds of nuclear division without cellular segmentation. after a number of nuclear divisions, the parasite cell will segment and merozoites are formed. there are situations where some of the sporozoites do not immediately start to grow and divide after entering the hepatocyte, but remain in a dormant, hypnozoite stage for weeks or months. the duration of latency is thought to be variable from one hypnozoite to another and the factors that will eventually trigger growth are not known; this might explain how a single infection can be responsible for a series of waves of parasitaemia or "relapses". it has been assumed that different strains of p. vivax have their own characteristic relapse pattern and timing. however, such recurrent parasitemia is probably being over-attributed to hypnozoite activation. two newly recognized, non-hypnozoite, probable contributing sources to recurrent peripheral p. vivax parasitemia are erythrocytic forms in bone marrow and the spleen. between 2018 and 2021, it was reported that vast numbers of non-circulating, non-hypnozoite parasites occur unobtrusively in tissues of p. vivax-infected people, with only a small proportion of the total parasite biomass present in the peripheral bloodstream. this finding supports an intellectually insightful, paradigm-shifting viewpoint, which had prevailed since 2011 (albeit not believed between 2011 and 2018 by most malariologists and therefore ignored), that an unknown percentage of p. vivax recurrences are recrudescences (having a non-circulating or sequestered merozoite origin), and not relapses (which have a hypnozoite source). the recent discoveries concerning bodily parasite biomass distribution did not give rise to this new theory; it was pre-existing, as explained above. the recent bone marrow and spleen, etc., findings merely confirm the likely validity of the theory. erythrocytic cycle microphotographs of plasmodium vivax in giemsa-stained thin blood films. a, b ring stages, c–e young trophozoites, f–h amoeboid trophozoites, i young schizont, j–l growing schizonts, m developed schizont, n mature schizont, o young gametocyte, p macroga‑metocyte, r, q microgametocytes. p. vivax preferentially penetrates young red blood cells (reticulocytes), unlike plasmodium falciparum which can invade erythrocytes. in order to achieve this, merozoites have two proteins at their apical pole (pvrbp-1 and pvrbp-2). the parasite uses the duffy blood group antigens (fy6) to penetrate red blood cells. this antigen does not occur in the majority of humans in west africa . as a result, p. vivax occurs less frequently in west africa. the parasitised red blood cell is up to twice as large as a normal red cell and schüffner's dots (also known as schüffner's stippling or schüffner's granules) are seen on the infected cell's surface. schüffner's dots have a spotted appearance, varying in color from light pink, to red, to red-yellow, as coloured with romanovsky stains. the parasite within it is often wildly irregular in shape (described as "amoeboid"). schizonts of p. vivax have up to twenty merozoites within them. it is rare to see cells with more than one parasite within them. merozoites will only attach to immature blood cell (reticulocytes) and therefore it is unusual to see more than 3% of all circulating erythrocytes parasitised. mosquito stage parasite life cycle in mosquitoes includes all stages of sexual reproduction: infection and gametogenesis microgametes macrogametes fertilization ookinite oocyst sporogony mosquito infection and gamete formation when a female anopheles mosquito bites an infected person, gametocytes and other stages of the parasite are transferred to the mosquito stomach. gametocytes ultimately develop into gametes, a process known as gametogony. microgametocytes become very active, and their nuclei undergo fission (i.e. amitosis) to each give 6-8 daughter nuclei, which becomes arranged at the periphery. the cytoplasm develops long thin flagella like projections, then a nucleus enter into each one of these extensions. these cytoplasmic extensions later break off as mature male gametes (microgametes). this process of formation of flagella-like microgametes or male gametes is known as exflagellation. macrogametocytes show very little change. they develop a cone of reception at one side and becomes mature as macrogametocytes (female gametes). fertilization male gametes move actively in the stomach of mosquitoes in search of female gametes. male gametes then enter into female gametes through the cone of reception. the complete fusion of 2 gametes results in the formation of zygote. here, fusion of 2 dissimilar gametes occurs, known as anisogamy. the zygote remains inactive for sometime but it soon elongates, becomes vermiform (worm-like) and motile. it is now known as ookinete. the pointed ends of ookinete penetrate the stomach wall and come to lie below its outer epithelial layer. here the zygote becomes spherical and develops a cyst wall around itself. the cyst wall is derived partly from the stomach tissues and partly produced by the zygote itself. at this stage, the zygote is known as an oocyst. the oocyst absorbs nourishment and grows in size. oocysts protrude from the surface of stomach, giving it a blistered appearance. in a highly infected mosquito, as many as 1000 oocysts may be seen. sporogony the oocyst nucleus divides repeatedly to form large number of daughter nuclei. at the same time, the cytoplasm develops large vacuoles and forms numerous cytoplasmic masses. these cytoplasmic masses then elongate and a daughter nuclei migrates into each mass. the resulting sickle-shaped bodies are known as sporozoites. this phase of asexual multiplication is known as sporogony and is completed in about 10–21 days. the oocyst then bursts and sporozoites are released into the body cavity of mosquito. sporozoites eventually reach the salivary glands of mosquito via its hemolymph. the mosquito now becomes infectious. salivary glands of a single infected mosquito may contain as many as 200,000 sporozoites. when the mosquito bites a healthy person, thousands of sporozoites are infected into the blood along with the saliva and the cycle starts again. taxonomy p. vivax can be divided into two clades one that appears to have origins in the old world and a second that originated in the new world. the distinction can be made on the basis of the structure of the a and s forms of the rrna. a rearrangement of these genes appears to have occurred in the new world strains. it appears that a gene conversion occurred in an old world strain and this strain gave rise to the new world strains. the timing of this event has yet to be established. at present both types of p. vivax circulate in the americas. the monkey parasite - plasmodium simium - is related to the old world strains rather than to the new world strains. a specific name - plasmodium collinsi - has been proposed for the new world strains but this suggestion has not been accepted to date. miscellaneous it has been suggested that p. vivax has horizontally acquired genetic material from humans. plasmodium vivax is not known to have a particular gram stain (negative vs. positive) and may appear as either. there is evidence that p. vivax is itself infected by viruses. therapeutic use p. vivax was used between 1917 and the 1940s for malariotherapy, that is, to create very high fevers to combat certain diseases such as tertiary syphilis. in 1917, the inventor of this technique, julius wagner-jauregg, received the nobel prize in physiology or medicine for his discoveries. however, the technique was dangerous, killing about 15% of patients, so it is no longer in use.