Phylum Apicomplexa Flashcards
Phylum Apicomplexa
Infective stages possess a cluster of microtubules and
organelles (the “apical complex”) at one end of the cell in certain stages of the life cycle
All the approximately 6,000 described sp. are endoparasites of animals
They alternate their life between the definitive host (where sexual reproduction occurs) and the vertebrate host (where adult stages are found)
These parasites cause malaria and malaria-like diseases in reptiles, birds, humans and other mammals.
Plasmodium and Haemoproteus produce the pigment hemozoin from hemoglobin when inside host erythrocytes.
Leucocytozoon does not.
Order Haemosporida
Macro and microgametocytes develop independently
Microgametocytes produce 8 flagellated gametes
Zygotes (Ookinetes) are actively motile
Sporozoites are not contained within sporocysts
Haemosporidians are heteroxenous (multiple hosts)
Merozoites in vertebrate host and sporozoites in invertebrate hosts
Haemosporidians infect diverse animals and cause mild disease
Malaria, however, often cause severe disease in humans.
Genus Plasmodium
It is most important human infectious disease
Malaria disease has often been associated with swamps with the common assumption that disease occurs by breathing “bad air” meaning “mal aria”.
It is also called marsh disease or paludism
Malaria vectors
An. gambiae (transmits P. falciparum)
An. stephensi (transmits P. vivax)
An. freeborni (transmits P. malariae)
An. funestus (transmits P. falciparum)
Plasmodium life cycle: vertebrate
Transmission of Plasmodium parasites starts by the bite of an infected female mosquito Anopheles mosquito.
Female Anopheles mosquito releases sporozoites while taking a blood meal
Sporozoites infect the hepatocytes in the liver and mature into schizonts which ruptures and releases merozoites. This is called exoerythrocytic schizogony
Released merozoites from the liver invades the red blood cells and undergo asexual reproduction in the erythrocytes (erythrocytic schizogony)
In the red blood cells, the ring stage trophozoites mature into schizont which rupture and release merozoites. Erythrocytic schizogony is repeated several times.
Some of the parasites differentiate into male and female gametocytes and remain in the peripheral blood
Pathology: Genus Plasmodium
Malaria is transmitted exclusively by female Anopheles mosquito
Fever paroxysm occurs over 6-10 hours and is initiated by synchronous rupture of erythrocytes with release of new infectious blood stage forms known as merozoites
Massive rupture of erythrocytes causes severe anemia
Transfusion induced malaria occurs when blood donors have subclinical malaria and may prove fatal for recipient
Similarly, congenital malaria may occur in infants of mothers from endemic areas; infant acquires infection at birth due to rupture of placental blood vessels with maternal fetal transfusion
Typically, no relapse with transfusion or congenital malaria because exoerythrocytic schizogony does not occur.
Signs and symptoms: Genus Plasmodium
Symptoms begin 10 days to 4 weeks after infection
Someone may feel ill as early as 7 days or as late as 1 year later.
P. vivax and P. ovale cause relapsing malaria
In P. vivax and P. ovale infections, some parasites can remain dormant in the liver for several months up to about 4 years after
a person is bitten by an infected mosquito.
Body aches and General malaise Elevated temperatures (fever) Loss of appetite Weakness Enlarged spleen (Splenomegaly) Mild jaundice Enlargement of the liver (hepatomegaly) Increased respiratory rate
Diagnosis: Genus Plasmodium
Detection of blood stages through Microscopy
Dipstick Rapid Diagnostic test
Molecular technique through PCR analysis
Treatment: Genus Plasmodium
The two most common antimalarial drugs:
Chloroquine phosphate: the preferred treatment for any parasite that is sensitive to the drug. In many parts of the world, parasites are resistant to chloroquine, and the drug is no longer an effective treatment.
Artemisinin-based combination therapies (ACTs): a combination of two or more drugs that work against the malaria parasite in different ways. This is usually the preferred treatment for chloroquine-resistant malaria.
Immunology: Genus Plasmodium
Hosts can mount a level of protective immunity, which can occur following initial infection and render the host shielded against subsequent disease.
Individuals who are repeatedly exposed to malaria develop antibodies against the sporozoite, liver-stage, blood-stage, and/or sexual-stage malaria antigens.
It is thought that antibodies acting directly against these antigens are responsible for the decreased susceptibility to malaria infection and disease seen in adults in malaria-infested areas.
Antibodies directed against the sexual stages of plasmodium may also reduce malaria transmission.
Naturally acquired immunity include the release of cytokines that act against all stages of the parasite and also a cytotoxic T cell response directed at liver stages of the parasite.
Vaccines: Genus Plasmodium
Pfs25 a 25 Kda (P. falciparum) protein is a leading malaria transmission-blocking vaccine antigen. It is expressed on the surface of zygotes and ookinetes in the mosquito midgut
Pfs28 (P. falciparum) protein blocks transmission when combined with antibodies to Pfs25. It provides synergy in blocking transmission. It’s an Ookinete surface protein
Pfs25-IMX313 is a Pfs25 plus a IMX313 molecular adjuvant ( a booster effect of the antigen)
RTS,S/AS01E is a P. falciparum circumsporozoite protein (CSP) antigen and the hepatitis B virus surface antigen (HBsAg). Leading candidate antigen that has shown 30-40% immunity. It is expressed together with HBsAg, and injected in combination with the AS01 adjuvant systemic
Risk factors: Genus Plasmodium
The greatest risk factor for developing malaria is living in or visiting areas
where the disease is common. These include tropical and sub tropical
regions of:
● Sub-Saharan Africa
● South and Southeast Asia
● Pacific Islands
● Central America and northern South America
People at risk for serious disease include:
Young children and infants (They haven’t developed specific immunity to
the infection)
Older adults
Travelers coming from areas with no malaria
Control: Genus Plasmodium
Use of prophylactic and chemotherapeutic drugs
Reduction of the contact between mosquitoes and humans
Destruction of larvae by environmental management
Use of larvicides for mosquito larvae
Biological control by use of larval predators,
Destruction of adult mosquitoes by indoor residual spraying by pyrethroid insecticides and use of insecticide-treated bed nets.
Vaccine development
Mutations and resistance: Genus Plasmodium
Thalassemia (reduced RBC & hemoglobin) in Mediterranean, Arab, and Asian populations;
The absence of the Duffy antigen / blood group in west Africa; Duffy antigen is a receptor for P. vivax
Hemoglobin E in Southeast Asia; and hemoglobin C in West Africa.
Mutation that causes sickle cell disease
Toxoplasma gondii life cycle
Oocysts from feces of cat definitive host contain two sporocysts, each with four sporozoites
Oocysts, if swallowed by an intermediate host, release sporozoites which infect various tissues
Sporozoites undergo endodyogeny to form merozoites (tachyzoites)
Tachyzoites infect tissues – muscles, liver & nerves and undergo asexual reproduction to form tissue cysts containing merozoites (bradyzoites)
A definitive host becomes infected when it consumes meat containing bradyzoites, which invades the intestinal lining and undergoes schizogony, gametogenesis and fertilization to produce oocysts
Immunity: Toxoplasma gondii
It involves both antibody (Th2) and cell mediated (Th1) responses
Th1 response is more important because most stages of the parasite are intracellular and antibody production is limited.
Th2 response is only against extracellular forms
Pathogenesis: Toxoplasma gondii
Factors affecting pathogenicity include:
• Virulence of the Toxoplasma strain
• Host age and susceptibility
• Degree of acquired immunity
Acute, sub-acute and chronic infections can occur.
Acute infections causes swelling of mesenteric lymph nodes.
Fever, headache, muscle pain and anemia could occur.
Chronic infection can affect the brain and other tissues in humans.
Congenital toxoplasmosis occurs through vertical transmission from mother to child during pregnancy.
Stillbirths and spontaneous abortion could occur from fetal infection.
Diagnosis and treatment: Toxoplasma gondii
Demonstration of parasite in biopsy or necropsy
Presence of Toxoplasma-specific antibody
ELISA test to confirm parasite antigen
Molecular techniques using PCR analysis
Pyrimethamine and sulfonamides are used together
Triclosan antibacterial compound can also be used
Epidemiology: Toxoplasma gondii
Cats are the primary source of infection to humans
Flies and cockroaches can serve as mechanical vectors, transmitting the oocysts from cat feces to human food
T. gondii tachyzoites have been recovered from nasal
cavity, saliva, eyes and urine
Blood transfusion and organ transplant are potential sources of serious infection
Human plasmodium parasites
P. falciparum (mainly in Africa). Malignant tertian. 48 hour paroxysms.
P. malariae (South America, Africa, Asia, E. Europe and S. pacific). Quartan malaria (72 hour paroxysms of fever)
P. vivax (mainly in Asia). Benign tertian
P. ovale (endemic to tropical W. Africa). Mild tertian
P. knowlesi (S. Asia) infects mammals including human, birds and reptiles.
Plasmodium life cycle: invertebrate
Male and female gametocytes are picked up during a blood meal by a female Anopheles mosquitoes
The parasite multiplication in the mosquito is known as the sporogonic cycle
While in the mosquito midgut the macro (female) and micro (male) gametocytes transform into macro and microgametes. The microgametocyte undergoes exflagellation producing 8 microgametes. Fertilization of the macrogametes by the microgametes produces a zygote
The zygote becomes motile and elongate ( Ookinetes) and invade the midgut wall (epithelium) of the mosquito where they develop into oocysts
The oocyst grows and ruptures, releasing sporozoites which makes their way into the mosquito salivary gland
The cycle starts again when the female mosquito feeds on another host
