Apicomlexa 2023 2

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Phylum Apicomplexa

• Class Sporozoea
• Subclass Coccidiasina
• Order Eucoccidiorida
• Suborder Haemosporina
• Genus Plasmodium
• Suborder Eimeriorina
• Genera Toxoplasma, Isospora,
Cryptosporidium
• Subclass Piroplasmasina
• Genus Babesia
The Coccidia (Family Eimeriina)
Toxoplasma gondii

• Presence of conoid.
• Three morphological
forms:
• Oocyst (product of the
sexual cycle in Cats,
contains sporocysts, which
contain sporozoites). Unsporulated oocyst
sporulated oocyst

• Tachyzoite (invasive form)


• Bradyzoites- (slow growing
merozoites in
Pseudocysts)
Apicomplexa enter mammalian cells by an active
parasite-driven process
Plasmodium

Toxoplasma
Strategy for intracellular survival by Apicomplexan parasites

• Cell invasion is active


• Excludes transmembrane proteins on
host plasma membrane from nascent
vacuole
• Intracellular residence in parasite
derived vacuole
• Associates with host ER and
mitochondria
• Ref. Traffic. 2000 Feb;1(2):100-6.
Internalization strategies of
intracellular parasites
amastigotes,
promastigotes and
large particles
Entry mechanisms and survival niches of intracellular
parasites
Intracellular parasite

Leishmania T. cruzi Toxoplasma

Cell types Primarily macrophages Variety All nucleated


Entry mechanism Phagocytosis Lysosome fusion Direct penetration
Niche Lysosomal Cytosolic Nonfusogenic vacuole

Julius Nyalwidhe, Uwe-Gallus Maier and Klaus Lingelbach. Intracellular parasitism: cell biological adaptations of parasitic protozoa to a life inside cells. Zoology 106 (2003): 341–348
Sibley LD and Andrews NW.Traffic. 2000 Feb;1(2):100-6. Cell invasion by un-palatable parasites.
Modes of transmission

Clin Microbiol Rev. 1998 Apr; 11(2): 267–299.


Entero-
epithelial
stage

Extra-
intestinal
stages
Epidemiology
• Toxoplasma is a zoonosis. Infects herbivores (rare in beef)
omnivores and carnivores.
• Worldwide distribution.
• Cats are important for parasite transmission but some
areas without cats have high prevalence.
• Cysts can be transmitted mechanically by roaches, flies…
• Major routes of transmission of Toxoplasma are oral
(ingestion of meat containing tissue cyst; contaminated
vegetables; other contaminated food products) and
congenital.
• Human to human transmission is rare except congenitally.
• Immunocompromised and during the first trimester of
pregnancy.
Toxoplasma control host behavior
• The infection is known to modify the behaviour of rodents,
causing decreased anxiety; decreased reaction speed;
decreased neophobia; impaired motor performance; lower
ability to discriminate between familiar and novel
surroundings; deficits in learning capacity and memory;
reduced specific predator avoidance; increased activity and
aggressiveness
• Rats can be more easily trapped when infected by
Toxoplasma, a situation which could simulate predation by
the felid final host
• These behavioural changes are often interpreted in terms
of the manipulation hypothesis, which proposes that
an animal serving as an intermediate host is manipulated
by the parasite to behave in a way to increase the
probability of being transmitted to the definitive host by
predation.

• [Gender differences in behavioural changes induced by


latent toxoplasmosis Int J Parasitol. 2006 Dec;36(14):1485-
92.]
Toxoplasma infection alters brain signaling in
rats

Reproductive Defensive Reproductive


pathway pathway pathway

AOB, accessory olfactory bulb; MEA, medial


amygdala; VMH, ventromedial hypothalamus.
PLoS One. 2011; 6(8): e23277.
• PLoS One. • Brain Behav Immun. 2014
2011;6(8):e23277. Feb;36:193-9..
• Predator cat odors • Toxoplasma gondii impairs
activate sexual arousal memory in infected seniors.
pathways in brains of • Gajewski PD1, Falkenstein M2,
Toxoplasma gondii Hengstler JG2, Golka K2.
infected rats.
• House PK1, Vyas A,
Sapolsky R.
• Schizophr Res. 2015 Jun;165(1):1-2. doi:
10.1016/j.schres.2015.03.036. Epub 2015 Apr 17.
• Is childhood cat ownership a risk factor for schizophrenia later in
life?
• Fuller Torrey E1, Simmons W2, Yolken RH3.
• Role for Toxoplasma?
Disease Presentation
Disease presentation cont’d
• Lymph nodes
• Toxoplasma encephalitis.
• Chorioretinitis.
• Chronic Toxoplasmosis can
affect other tissues.
• hypersensitivity reaction to
pseudocysts.
• Congenital infections
spontaneous abortions.
hydrocephalus is a likely
occurrence.
Immunity

• Rare clinical cases of reinfection (can become immune).

• Opportunistic parasite. Host protection is mediated by


CD4+ T cells. CD8+ T cells play significant protective role in
immunocompetent host. They lyse infected host cells.
• Interferon gamma produced by CD4+ T cells limits parasite
replication in host cells.
• Antibodies also play a role. Mediate lysis of released
tachyzoites.
Diagnosis and Prevention
• During acute infection parasite can be detected in blood.
• Serology, demonstration of antibody to parasite is primary
diagnostic method.

• Prevention. Most important in seronegative pregnant


women. Avoid ingestion of, and contact with cysts or
sporulated oocysts.
• Cook meat to 66oC. Gamma irradiation, freeze to –20 C
then thaw.
• Avoid cat feces during pregnancy.
• Treatment: Pyrimethamine
Phylum Apicomplexa
• Class Sporozoea
• Subclass Coccidia
• Order Eucoccidia
• Suborder Haemosporina
• Genus Plasmodium
• Suborder Eimeriina
• Genera Toxoplasma, Cryptosporidium, Isospora
• Subclass Piroplasmia
• Genus Babesia
Babesia
• Plasmodium – like
• Infects red blood cells.
• Primarily infect cattle, birds, rodents and other animals
• Babesia microti, B. bovis are species that infect humans.
Zoonosis
• Transmitted by ticks – Ixodus dammini (Ixodus scapularis)
that also transmits Borrelia burgdofori (causative agent of
lyme disease).
• Ticks have three developmental stages (larva, nymph,
adult) that each require blood for development. Nymph
stage most significant in human infection. (trans-
stadial transmission – from larva to nymph). Ticks feed on
deer, but deer are not infected with Babesia; rodents are.
• Infected adult ticks pass Babesia transovarially to progeny.
Babesia life cycle/transmission

Larval ticks acquire parasites;


nymphs are the tick form that
feed on humans
Infect Dis Clin North Am. 2015 Jun;29(2):357-70
Epidemiology and Pathogenesis
• Found in Eastern United States. Important
enzootic foci in Nantucket, Martha’s
Vineyard MA, Long Island, Northern
Midwest states and Western U.S.
• Also found in Europe. Most cases have been
in splenectomized persons. Unlike U.S
where majority of people infected were
immunocompetent.
• Incubation period after tick bite is 1-3
weeks. Parasite causes mild disease in
healthy indviduals.
• Fever, hemolysis, hemoglobinuria.
• Can be fatal in splenectomized.
• Parasite in blood should be limited by
humoral responses. Can undergo antigenic
variation.
Diagnosis and Treatment
• Presence of parasite in blood (no exoerythocytic stages).
• Can be confused with P. falciparum (presence of ring
stages). Have no hemozoin or Maurer’s clefts as is
sometimes seen in P. falciparum-infected cells.
• Serology – detection of anti-Babesia antibody by IFA…

• Disease self limiting


• Treated with Clindamycin (Chloroquine not effective)
• Prevention: avoid endemic areas during months of peak
transmission (May to September).
• Use Diethytoluamide (deet) insect repellant sprayed on
skin. Check pets for ticks.

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