Plasmodium vivax
Erika L. Flannery,1,
* Miles B. Markus,2
and Ashley M. Vaughan3
1
Novartis Institute for Tropical Diseases, Emeryville, CA, USA
2
University of Witwatersrand, Johannesburg, South Africa
3
Seattle Children’s Research Institute, Seattle, WA, USA
Plasmodium vivax is the most widely distributed of several plasmodial species that cause human malaria, a disease
associated with blood-stage parasite replication. About 2.5 billion people are at risk of P. vivax infection; they live
mainly in Southeast Asia and the Americas, where P. vivax accounts for approximately 72% of malaria cases. In
Africa, widespread lack of the Duffy antigen constrains transmission. The dormant liver form of the parasite, the
hypnozoite, which can reactivate long after the primary infection and give rise to a relapsing blood-stage infection,
complicates eradication. In fact, hypnozoites are the origin of most blood-stage infections. Primaquine and
tafenoquine are the only drugs that prevent relapse. However, neither is used during pregnancy or by people
with glucose-6-phosphate dehydrogenase deficiency; and tafenoquine is not yet approved for treating children.
Thus, this species of malaria-causing parasite is a unique challenge in eradication campaigns.
KEY FACTS:
Sporozoites of P. vivax are injected into
the human skin by a mosquito and
migrate to the liver, where a clinically
silent phase of either parasite
multiplication (schizogony) or dormancy
occurs per sporozoite. Both forms of the
parasite (schizont and hypnozoite) can
exist simultaneously in the liver.
The transition from liver stage to blood
stage results in asexual parasite
expansion in erythrocytes. Sexual-stage
gametocytes also develop in
erythrocytes and are taken up during a
mosquito blood meal, after which mature
gametes fuse. Ultimately, midgut
oocysts mature, releasing sporozoites
that travel to the mosquito's salivary
glands.
The nuclear genome is 29 Mb, encoding
6642 genes; the mitochondrial genome
is 6 kb; and the apicoplast genome is
29.6 kb.
DISEASE FACTS:
Asexual blood-stage reproduction leads
to illness involving febrile episodes,
anemia, diarrhea, abdominal pain,
nausea and vomiting, headache, and
muscular pains. Disease consequences
include organ failure, respiratory
problems, splenomegaly, splenic rupture
and occasionally death.
P. vivax is a major cause of suffering in
resource-poor settings.
Continuous reinfection or superinfection
is frequent, but is usually subclinical.
Patients may experience relapses after
weeks to years, because of (presumed)
hypnozoite activation.
TAXONOMY AND CLASSIFICATION:
PHYLUM: Apicomplexa
CLASS: Aconoidasida
ORDER: Haemosporida
FAMILY: Plasmodiidae
GENUS: Plasmodium
SPECIES: P. vivax
*Correspondence:
erika.flannery@novartis.com (E.L. Flannery).
Immature
Maturing
schizont
Schizont
releasing
merozoites
Early liver stages
Migrating
sporozoite
Gametes
Macrogametocyte
Microgametocyte
Early
oocyst
hypnozoite
Mosquito midgut
Invading
sporozoite
Skin
capillary
Skin
Salivary gland
sporozoites
Midgut oocyst
releasing
Ookinete
Midgut epithelium
Gamete
Sporozoite inoculation
during skin probing
Gametocyte transmission
during blood meal
acquisition
Liver stage
development
Maturing
oocyst
sporozoites
Zygote
schizont
Dormant
Liver
sinusoid
Ring stage
Merozoites
Bloodstream
Asexual bloodstage
replication
Schizont
Trophozoite
infection
Sporozoite transmission
and liver stage infection
Salivary gland
invasionHemolymph
LiverMosquito stage
development
Gametocyte
maturation
Blood meal
TrendsTrendsininParasitologyParasitology
Hypnozoite
Day 8
schizont
: DNA
: Parasitophorous
vacuole membrane
: Parasite histone H3
Scale bar:10
Liver stage Key biological and epidemiological differences
Species Plasmodium vivax Plasmodium falciparum
Infective gametocytes
in bloodstream
Present earlier (leads to
earlier transmission)
Transmission occurs
later
Sporogony in
mosquito
Duration shorter
(facilitates transmission)
Longer duration
Development in
mosquito
Can occur in temperate
regions, thus widespread
geographically
Higher temperatures
required and therefore
less widespread
Parasite density in
peripheral blood
Low (infection very easily
overlooked)
Can be very high
Parasite population
genetic diversity
High global diversity Less diverse
Hypnozoite stage in
liver
Yes Not known to occur
Mortality Infrequent Frequent
Immunity Acquired quickly Acquired slowly
TrendsTrendsininParasitologyParasitology
Trends in Parasitology, July 2019, 35, No. 7 © 2019 Published by Elsevier Ltd. https://doi.org/10.1016/j.pt.2019.04.005 583
Trends in Parasitology | Parasite of the Month
Resources
www.malariaeradication.org/
www.who.int/malaria/en/
www.cdc.gov/malaria/
www.plasmodb.org
www.mmv.org
Literature
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Res. 1, 4
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Front. Microbiol. 9, 1271
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Trends in Parasitology | Parasite of the Month
584 Trends in Parasitology, July 2019, 35, No. 7 © 2019 Published by Elsevier Ltd. https://doi.org/10.1016/j.pt.2019.04.005