Plasmodium vivax

Plasmodium vivax is a protozoal parasite and a human pathogen. The most frequent and widely distributed cause of recurring (tertian) malaria, P. vivax is one of four species of malarial parasite that commonly infect in humans. It is less virulent than Plasmodium falciparum, the deadliest of the four, and seldom fatal. P. vivax is carried by the female Anopheles mosquito, since it is the only sex of the species that bites.

Health

Epidemiology

P. vivax is found mainly in Asia, Latin America, and in some parts of Africa. P. vivax can cause death due to splenomegaly (a pathologically enlarged spleen), but more often it causes debilitating – but non-fatal – symptoms.

Treatment

Chloroquine remains the treatment of choice for vivax malaria, except in Indonesia's Irian Jaya (Western New Guinea) region and the geographically contiguous Papua New Guinea, where chloroquine resistance is common (up to 20% resistance). When chloroquine resistance is common or when chloroquine is contraindicated, then artesunate is the drug of choice, except in the U.S. where it is not approved for use; mefloquine is a good alternative and in some countries is more readily available. Atovaquone-proguanil is an effective alternative in patients unable to tolerate chloroquine. Quinine may be used to treat vivax malaria but is associated with inferior outcomes.

32 to 100% of patients will relapse following successful treatment of P. vivax infection if a radical cure (eradication of liver stages) is not given. Eradication of the liver stages is achieved by giving primaquine, after checking the patients G6PD status to reduce the risk of haemolysis. Recently, this point has taken particular importance for the increased incidence of vivax malaria among travelers.

Eradication Efforts in Korea

P. vivax is the only indigenous malaria parasite on the Korean peninsula. In the years following the Korean War (1950-53), malaria-eradication campaigns successfully reduced the number of new cases of the disease in North Korea and South Korea. In 1979, World Health Organization declared the Korean vivax malaria-free but the disease unexpectedly re-emerged in the late 1990s and still persists today. Several factors contributed to the re-emergence of the disease, including reduced emphasis on malaria control after 1979, floods and famine in North Korea, emergence of drug resistance and possibly global warming. Most cases are identified along the Korean Demilitarized Zone. As such, vivax malaria offers the two Koreas a unique opportunity to work together on an important health problem that affects both countries.

Biology

P. vivax can reproduce both asexually and sexually, depending on its life cycle stage.

Asexual forms:

Immature trophozoites (Ring or signet-ring shaped), about 1/3 of the diameter of a RBC.
Mature trophozoites: Very irregular and delicate (described as amoeboid); many pseudopodial processes seen. Presence of fine grains of brown pigment (malarial pigment) or hematin probably derived from the haemoglobin of the infected red blood cell.
schizont (also called meronts): As large as a normal red cell; thus the parasitized corpuslce becomes distended and larger than normal. there are about sixteen merozoites.

Sexual forms: Gametocytes: Round. The gametocytes of P. vivax are commonly found in the peripheral blood at about the end of the first week of parasitemia.

Life Cycle

The incubation period for the infection usually ranges from ten to seventeen days and sometimes up to a year. Persistent liver stages allow relapse up to five years after elimination of red blood cell stages and clinical cure.

Human Infection

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 certain 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 variable from one hypnozoite to another and the factors that will eventually trigger growth are not known; this explains how a single infection can be responsible for a series of waves of parasitaemia or "relapses". Different strains of P. vivax have their own characteristic relapse pattern and timing.

Erythrocytic Cycle

P. vivax preferentially penetrates young red blood cells (reticulocytes). 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 (Fya and Fyb) as receptors to penetrate red blood cells. These antigens do not occur in the majority of humans in West Africa [phenotype Fy (a-b-)]. As a result P. vivax does not occur in West Africa.

Microscopically, the parasitised red blood cell is up to twice as large as a normal red cell and Schüffner's stippling (also known as Schüffner's dots or Schüffner's granules) is seen on the infected cell's surface, the spotted appearance of which varies 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"). schizont 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.

Sexual Stage

Mosquito Stage

Laboratory Considerations

P. vivax and P. ovale that has been sitting in EDTA for more than half-an-hour before the blood film is made will look very similar in appearance to P. malariae, which is an important reason to warn the laboratory immediately when the blood sample is drawn so they can process the sample as soon as it arrives. Blood films are preferably made within half-an-hour of the blood being drawn and must certainly be made within an hour of the blood being drawn.