|Mature P. vivax trophozoite|
Grassi & Feletti 1890
Plasmodium vivax is a protozoal parasite and a human pathogen. The most frequent and widely distributed cause of recurring (Benign tertian) malaria, P. vivax is one of the six species of malaria parasites that commonly infect humans. It is less virulent than Plasmodium falciparum, the deadliest of the five, but vivax malaria can lead to severe disease and death due to splenomegaly (a pathologically enlarged spleen).  It afflicted as many as eight U.S. presidents—including George Washington and Abraham Lincoln—and may have helped kill Genghis Khan. P. vivax is carried by the female Anopheles mosquito, since it is only the female of the species that bite.
- 1 Health
- 2 Biology
- 3 Laboratory considerations
- 4 Taxonomy
- 5 Therapeutic use
- 6 See also
- 7 References
- 8 External links
The World Health Organization (WHO) is drawing up a plan to address vivax malaria, due out in 2015.
P. vivax was found mainly in the United States, Latin America, and in some parts of Africa. More recently it became a plague of low- and middle-income countries, except those in sub-Saharan Africa, where the P. vivax map has a conspicuous hole. Overall it accounts for 65% of malaria cases in Asia and South America.
Although the Americas contribute 22% of the global area at risk, high endemic areas are generally sparsely populated and the region contributes only 6% to the total population at risk. In Africa, the widespread lack of the Duffy antigen in the population has ensured that stable transmission is constrained to Madagascar and parts of the Horn of Africa. It contributes 3.5% of global population at risk. Central Asia is responsible for 82% of global population at risk with high endemic areas coinciding with dense populations particularly in India and Myanmar. South East Asia has areas of high endemicity in Indonesia and Papua New Guinea and overall contributes 9% of global population at risk.
P. vivax is carried by at least 71 mosquito species. Many vivax vectors live happily in temperate climates—as far north as Finland. Some prefer to bite outdoors or during the daytime, hampering the effectiveness of indoor insecticide and bed nets. Several key vector species have yet to be grown in the lab for closer study, and insecticide resistance is unquantified.
Course of disease
Unlike P. falciparum, P. vivax can populate the bloodstream with sexual-stage parasites—the form picked up by mosquitoes on their way to the next victim—even before a patient shows symptoms. That means that promptly treating symptomatic patients doesn't necessarily help stop an outbreak, as it does with falciparum malaria, in which fevers occur as sexual stages develop. Even when symptoms appear, because they are usually not immediately fatal, the parasite continues to multiply.
The parasite can go dormant in the liver for days to years, causing no symptoms and remaining undetectable in blood tests. They form what are called hypnozoites (the name derives from "sleeping parasites"), a small form that nestles inside an individual liver cell. The hypnozoites allow the parasite to survive in more temperate zones, where mosquitoes bite only part of the year.
A single infectious bite can trigger six or more relapses a year, leaving sufferers more vulnerable to other diseases. Other infectious diseases, including falciparum malaria, appear to trigger relapses.
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). Chloroquine resistance is an increasing problem in other parts of the world, such as Korea and India.
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. Where an artemisinin-based combination therapy has been adopted as the first-line treatment for P. falciparum malaria, it may also be used for P. vivax malaria in combination with primaquine for radical cure. An exception is artesunate plus sulfadoxine-pyrimethamine (AS+SP), which is not effective against P. vivax in many places. 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.
Eradication of the liver stages is achieved by giving primaquine. Patients with glucose-6-phosphate dehydrogenase (G6PD) deficency risk haemolysis. G6PD is an enzyme important for blood chemistry. No field-ready test is available. Recently, this point has taken particular importance for the increased incidence of vivax malaria among travelers. At least a 14-day course of primaquine is required for the radical treatment of P. vivax.
In 2013 a Phase IIb trial was completed that studied a single-dose alternative drug named tafenoquine. It is an 8-aminoquinoline, of the same family as primaquine, developed by researchers at the Walter Reed Army Institute of Research in the 1970s and tested in safety trials. It languished, however, until the push for malaria elimination sparked new interest in primaquine alternatives.
Among patients who received a 600-mg dose, 91% were relapse-free after 6 months. Among patients who received primaquine, 24% relapsed within 6 months. "The data are absolutely spectacular," Wells says. Ideally, he says, researchers will be able to combine the safety data from the Army's earlier trials with the new study in a submission to the U.S. Food and Drug Administration for approval. Like primaquine, tafenoquine causes hemolysis in people who are G6PD deficient.
In 2013 researchers produced cultured human "microlivers" that supported liver stages of both P. falciparum and P. vivax and may have also created hypnozoites.
Mass-treating populations with a primaquine can kill the hypnozoites, exempting those with G6PD deficiency. However, the standard regimen requires a daily pill for 14 days across an asymptomatic population.
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 peninsula 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 an opportunity to work together on an important health problem that affects both countries.
P. vivax can reproduce both asexually and sexually, depending on its life cycle stage.
- 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.
- 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. The gametocytes of P. vivax are commonly found in the peripheral blood at about the end of the first week of parasitemia.
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.
The infection of Plasmodium vivax takes place in human when an infected female anopheles mosquito sucks blood from a healthy person. During feeding, the mosquito injects saliva to prevent blood clotting (along with sporozoites), thousands of sporozoites are inoculated into human blood; within a half-hour the sporozoites reach the liver. There they enter hepatic cells, transform into the tropozoite form and feed on hepatic cells, and reproduce asexually. This process gives rise to thousands of merozoites (plasmodium daughter cells) in the circulatory system and the liver.
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. The earlier stage is exo-erythrocytic generation.
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 (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) 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"). 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.
The sexual stage includes following processes by which P. vivax reproduces sexually:
- Transfer to mosquito
the life cycle in mosquitoes include:
Formation of gametes
Development of gametes from gametocytes is known as gametogony. When a female Anopheles mosquito bites an infected person, gametocytes and other stages of the parasite are transferred to the stomach where further development occur.
The microgametocytes becomes very active and its nucleus undergoes fission to 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. It develops a cone of reception at one side and becomes mature as female gamete / macrogameto cytes.
Male gametes move actively in the stomach of mosquito in search of female gamete. Male gamete then enters into female gamete through the cone of reception and the complete fusion of 2 gametes result in the formation of zygote. (synkaryon). Process of fusion of male and female gamete is called as syngamy. Fusion of 2 dissimilar gametes is 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 wall of stomach and comes to lie below its outer epithelial layer. Here it 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, it is known as the oocyst. The oocyst absorbs nourishment and grow in size. These oocyst protrude (bulge) from the surface of stomach giving it a kind of blistered appearance. In a highly infected mosquito, as many as 1000 oocyst may be seen.
The nucleus of oocyst 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 one of them. The resulting sickle-shaped bodies is known as sporozoites. This phase of asexual multiplication is known as sporogony and is completed in about 10–21 days. The oocyst then burst and sporozoites are released into the body cavity of mosquito from where they eventually reach the salivary glands of mosquito through blood. The mosquito now becomes infective . 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.
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. Diagnosis can be done with the strip fast test of antibodies,
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.
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 sphyillis. In 1917, the inventor of this technique, Julius Wagner-Jauregg, received the Noble Prize in physiology or medecine for his discoveres. However, the technique was dangerous, killing about 15% of patients, so it is no longer in use.
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