Life cycle Like all
malaria parasites,
P. vivax has a complex life cycle. It infects a definitive insect
host, where
sexual reproduction occurs, and an intermediate vertebrate host, where
asexual amplification occurs. In
P. vivax, the definitive hosts are
Anopheles mosquitoes (also known as the
vector), while humans are the intermediate asexual hosts. During its life cycle,
P. vivax assumes various different physical forms (see below). Asexual forms: •
Sporozoite: Transfers infection from mosquito to human • Immature
trophozoites (ring or signet-ring shaped), about one-third of the diameter of a
red blood cell. • Mature trophozoites: Very irregular and delicate (described as
amoeboid); many
pseudopodial processes seen. The presence of fine grains of brown pigment (malarial pigment) or
hematin is probably derived from the
haemoglobin of the infected red blood cell. •
Schizonts (also called meronts): As large as a normal red cell; thus the parasitized corpuscle becomes distended and larger than normal. There are about sixteen merozoites. Sexual forms: •
Gametocytes: Round.
P. vivax gametocytes are commonly found in human peripheral blood at about the end of the first week of
parasitemia. •
Gametes: Formed from gametocytes in mosquitoes. •
Zygote: Formed from combination of gametes •
Oocyst: Contains zygote, develops into sporozoites
Human infection P. vivax human infection occurs when an infected mosquito feeds on a human. During feeding, the mosquito injects
saliva, along with sporozoites, through the skin. A proportion of these sporozoites reach the
liver. There they enter
hepatic cells, on which they feed, and reproduce asexually, as described in the next section. This process gives rise to thousands of
merozoites (plasmodial daughter cells) in the body. The
incubation period of human infection usually ranges from ten to seventeen days and sometimes up to a year. Persistent liver stages allow relapse up to five years after the elimination of red blood cell stages and clinical cure.
Liver stage The
P. vivax sporozoite enters a hepatocyte and begins its exo
erythrocytic schizogony stage. This is characterized by multiple rounds of
nuclear division without cellular segmentation. After several 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 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 [phenotype Fy (a-b-)]. 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 cells (reticulocytes) and therefore it is unusual to see more than 3% of all circulating erythrocytes parasitised. Unusual erythrocytic forms were detected in a few cases of an outbreak in Brazil.
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's 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 become arranged at the periphery. The
cytoplasm develops long thin
flagella-like projections, then a nucleus enters 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 become 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 a
zygote. Here, the fusion of 2 dissimilar gametes occurs, known as
anisogamy. The zygote remains inactive for some time but it soon elongates and becomes vermiform (worm-like) and
motile. It is now known as an
ookinete. The pointed ends of the 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 the 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 a 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 migrate 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 mosquitoes. Sporozoites eventually reach the
salivary glands of mosquitoes via its
hemolymph. The mosquito now becomes infectious. The 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 injected 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 based on 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. == Health ==