Micro Chapter 51: Intro to Parasitology
A lot of adults in te US are infected with toxoplasma gondii, and show antitoxoplasma antibodies
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But very few show disease and become ill from the infection
Example of how infection and disease are different
Hookworms eat a small amount of blood, so a few worms infection is asymptomatic, while more
cause disease
Since parasites depend on the host for their survival and life cycle, they don’t want to kill the host
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Disease from parasites is often from prolonged ,repeated, or unusually burdensome infection
Parasitic disease is usually subacute or chronic, and rarely fatal over short periods
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Exceptions – malaria (plasmodium falciparum) is rapidly fatal
Parasites that usually cause no problems in a otherwise healthy person, can cause disease in
immunocompromised people
Several parasitic infections are zoonoses – they are caused by agents that infect animals
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Many human parasites need both human and nonhuman hosts to complete their life cycles
In other cases, they don’t need multiple hosts, and just infect humans, making us “dead-end
hosts”
Schistosome (aka “blood fluke”) cause “swimmer’s itch”
Protozoa are one celled eukaryotes
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Clinically relevant protozoa are plasmodium (malaria), toxoplasma, giardia, cryptosporidium,
leishmania, and trypanosomes
It doesn’t take much inoculum (much of them) to cause infection
Disease by protozoa is usually caused by replication of the protozoa in large #’s in the host
Replication can be both intracellular or extracellular
Since protozoa are unicellular with just a cell membrane, they aren’t able to withstand
dessication (drying) in the external environment
o So their life cycles don’t involve a free environmental stage
Protozoa are transmitted from one host to another by arthropod vectors
o Ex: plasmodia are transmitted by mosquitoes
Other protozoa alternate between two forms:
o An active trophozoite form – grows and replicated by binary fission int eh host
o A dormant, nonreplicating cyst form – adapted for survival in environments during
transit between hosts
 Protozoa cysts are pretty impermeable because of their double membranes,
helping them resist dessication in the external environment
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 Protozoa that infect the GI do this
Classifying protozoa:
o Amebas (aka sarcodina) – formless cells that move purposefully by extending
pseudopods toward an attractive stimulus, and then streaming their cytoplasm in the
desired direction
 Amebas are intestinal parasites that alternate between trophozoite and cyst
forms
o Flagellates – protozoa that use one or more flagella to move
 They can form cysts, and blood ones are transmitted by arthropods
o Ciliates – protozoa covered with tiny cilia that allow movement
o Apicomplexans (sporozoa) – important pathogens that do intracellular replication
 They move using a “tractor-tread” mechanism of gliding motility, which allows
them to enter cells
 Includes malaria, toxoplasmosis
Helminthes (worms) – multicellular animals (metazoa), and are much bigger than protozoa
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Because they reproduce sexually, infections need both male and female worms
o Some tapeworms though are hermaphroditic and have both male and female parts
Roundworms – look circular on cross section
o Ascaris lumbricoides look a lot like earthworms, except it doesn’t have any visible body
segmentation
Flatworms – look asymmetric in cross section
o Two types of flatworms:
 Flukes – short flatworms with nonsegmented bodies
 Includes schistosoma
 Tapeworms – segmented flatworms, that act as a colony, where the worm head
adds to a growing chain of flat segments, each with its own nutrional and
reproductive organs
Worms are big and usually extracellular
Helminthes are protected by an impermeable cuticle
No helminthes parasite completes its life cycle within a single human host
o So disease is not normally a consequence of helminthes growing in # int eh host, like it is
in protozoa
Instead, disease is caused by acquiring multiple helminthes from the environment
Vectors – living transmitters of disease
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Most vectors are arthropods
Ex: female anopheles mosquitoes transmit malria
Arthropods can also transmit bacteria and viruses
Arthropods are also involved in essential steps of the parasite life cycle
o Ex: parasitic disease depends on whether conditions are favorable for the arthropod
Reservoirs – sources of parasites itn eh environment that don’t participate directly in transmission to
humans
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Reservoirs of human parasites include other humans (ex: malaria), animals (pigs for trich), and
the environment (soil contaminated with parasitized feces)
Parasite entry into the host can be by fecal-oral route, direct penetration of unbroken skin infections, or
bites by arthropod vectors
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Ingesting contaminated food or water by human waste is a common source of entry of parasites
Parasites elicit both B cell and T cell responses, but they’re good at avoiding them
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Adult schistosomes (blood flukes) coat themselves with host plasma proteins, and are therefore
not recognized as foreign by the immune system, which lets them hang out in the host for
decades
Trypanosomes, plasmodia, and giardia vary their surface antigens
Page 501 – bottom box
Temperature plays an important role in the ability of parasites to infect humans and cause disease
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Some parasites prefer some temperatures over others
Temperature changes also induce stage-specific transitions in many parasites
o Ex: leishmania change from the promastigote form to the amastigote form as it goes
from cold to hot
Some parasites cause direct damage to tissues, and others cause disease through the immune response
against them
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Many parasites in deep tissues elicit an ineffective acute inflammatory response
Chronic inflammation is the hallmark of parasite diseases like schostosomiasis and cutaneous
filiariasis
In some parasites, the adult doesn’t cause issue, but the progeny trigger inflammatory
responses when they degenerate in host tissues
Eosinophils are WBCs that work in neutralizing infections with parasitic worms
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Worm infections often show eosinophilia (lots of eosinophils in the blood)
Helminthes surface glycoproteins and polysaccharides trigger the eosinophils
Eosinophilia is usually accompanied by increased levels of IgE, and is driven by elevated levels of
Il-5
Levels are increased when the helminthes gets into deep tissues
Eosinophilia doesn’t happen though in protozoa infections, or when the helminthes doesn’t
cross through tissue
Often the environment determines if a parasite can infect us
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Ex: schistosomiasis depends on intermediate snail host that is not found in north America or
Europe
o So viable eggs int eh stool or urine of an infected person can’t produce the cercariae
form that infects humans, because there is no snail host ot mature in
o So schistosomaiasis is not endemic in the US, and will not be, no matter how many
infected people come over here
However the mosquitoes that carry malaria in Africa, are also found in the US
o So infected people can serve as a meal for our mosquitoes, and now the virus can
mature and infect new people
Page 503 – parasite life cycle
Antiparasite strategies are drugs to prevent and treat, immunization, and control measures in the
environment to prevent (like wearing shoes)
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Chemoprophylaxis – drugs used to prevent infection
o These drugs are more strict on side effects, because they’re gonna be taken for much
longer than short term drugs to eradicate infections
o Ex: so you can’t be having nausea every day from the drug
o Ex: chloroquine was used to prevent malaria – it worked against all 4 strains of
plasmodium
 Unfortunately, malaria become resistant to chloroquine
Vaccines are hard to make, cause parasites are good at avoiding immune defense anyways, and
you’d have to make them for different stages of the parasite life cycle
Micro Chapter 52: Blood and Tissue Protozoa
Protozoa bloodstream infections, like malaria and babesiosis, often involve infection and destruction of
RBCs
Page 508 – blood and tissue protozoa
Parasites of RBCs:
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Plasmodium – cause malaria
o Malaria is the most important of all protozoal diseases
o Malaria is often found in tropical areas
o Malaria in humans is caused by 4 plasmodium species: P. falciparum, P. vivax, P. ovale,
and P. malariae
o Infected humans are the only reservoir for these plasmodium that infect humans
o Transmission of malaria happens by bite of infected female anopheline mosquitoes
 The transmission happens 9-17 days after the mosquito took blood from an
infected person
 The infected person then develops malaria symptoms 8-30 days later
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Most cases of malaria in the US or Europe were acquired in endemic areas, and tehn
imported into nonednemic areas during the incubation period
Anopheles mosquitoes that can be vectors are also found in the US, allowing rarely for
people who have never traveled to catch malaria
Malaria can also be transmitted by blood transfusions and needles (induced malaria)
In the infected mosquito, plasmodia inhabit the salivary glands as sporozoites, a stage of
the parasite that is infectious for humans
 sporozoites are put into human blood when the infected mosquito bites you
 the plasmodium sporozoite then travels through te blood to the liver cells
within a half hour of injection
 Over the next 1-2 weeks, the parasites multiply and mature inside liver cells to
very large #’s, this is called the hepatocellular cycle
 At the end of that cycle ,they’re released back into the blood as a form called
merozoites, which can invade RBCs
 Once in the RBC, the plasmodiums divide and mature
 After 2-3 days, the RBCs burst, freeing a new generation of infective merozoites,
that then infect new RBCs, this is called the eyrthrocytic cycle
In the liver and RBCs, the parasites multiply asexually through fission
A minority of the merozoites in the blood develop into forms capable of sexual
reproduction, called gametocytes
 Male and female gametocytes are taken up by biting mosquitoes
 In the mosquito gut, the haploid male and female gametes fuse to form a
diploid zygote, which is the sexual part of the malaria life cycle
After the zygote is formed, the parasites changes more in the mosquito gut, and then
divides by meiosis to generate sporozoites
 Sporozoites migrate to the salivary glands, and once again become infective for
humans
Different plasmodium species prefer RBCs of different ages
 P. falciparum invades RBCs of all ages, causing the most parsitemia and greatest
risk for mortality with malaria
 P. vivax prefers reticulocytes and young RBCs
 P. malariae prefers old RBCs
 Both P. vivax and P. malariae then infect a small minority of RBCs, causing less
severe disease
 P. ovale is pretty much identical to P. vivax
 P. ovale and P. vivax are unique in that hepatocytes can hold them for a while
before they get released into blood, allowing for relapses months or years after
the initial episode
 Latent parasites are called hypnozoites
The intracellular location of the plasmodium in the RBC has 2 consequences:
 The presence of plasmodia in RBCs makes the RBC less deformable
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The spleen recognizes and removes less deformable RBCs, so it’s good
at removing parasitized RBCs
 This is why malaria causes splenomegaly, and people without a spleen
have more severe malaria infections
 A RBC infected with P. falciparum develops special “knoblike” structures on its
surface, that have the parasite-derived protein pfEMP-1
 pfEMP1 binds the infected RBC to receptors on endothelial cells of
venules and capillaries (ex: the receptor intercellular adhesion molecule
1 (ICAM-1) and CD36)
 When multiple parasitized RBCs adhere and accumulate on the
endothelium, blood flow through the deep vascular beds is impeded
 So P. falciparum-infected cells are prevented from circulating to the
spleen and being removed from circulation, but this can hurt the host
The main symptoms of malaria are fever, chills, and anemia
 These are noticed when the RBCs lyse and release lots of merozoites
 When this happens, parasite molecules are also released, like
glycophosphatidylinositol (GPI)
 GPI and other molecules stimulate the making of TNF and Il-1 in macrophages
 The surge in those cytokines is the stimulus for sudden chill and fever
characteristic of malaria
Parasite replication can become synchronized so that al infected RBCs lyse at the same
time
 This causes regular periodic fever patterns to develop, depending on the length
of the intracellular replication cycle (2 dyas for P. vivax and P. ovale, and 3 for P.
malariae)
 P. falciparum has an irregular fever pattern
Other malaria symptoms include flu symptoms (fever, musche aches, and malaise) and
gastroenteritis symptoms (nausea, diarrhea, and vomiting)
Malaria is diagnosed by microscope exam by a Giemsa-stained smear of blood
P. falciform or P. vivax are usually the cause of acutely ill patients, while P. malariae
most often causes subacute or chornic infections, but can produce acute infections in
immunosuppressed people
 P. ovale is so similar to P. vivax, that distinction between the two is unimportant
P. vivax causes infected RBCs to progressively enlarge as the parasite matures and
produces eosinophilic “stippling” in the RBCs (Schuffner dots)
 There is no RBC enlargement or Schuffner dots with P. falciparum
Even people who live in areas endemic to malaria, and have immunity built up to it, will
still be infected, but their disease will be less severe
 The major surface protein of the merozoite stage (MSP-1) is capable of
undergoing antigenic variation
Human genetic variations can play a role in malaria
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Parasite invasion of RBCs depends on there being specific surface molecules
 For p. falciparum and P. vivax, the surface molecules are glycophorin A,
and the duffy blood group antigen, respectively
 Black Africans are usually Duffy-negative, and therefore resistant to P.
vivax infection
 Sickle cell disease – recessive genetic disorder that causes RBCs to become rigid
and elongated when there is less oxygen
 Sickle cell is common in areas of Africa that have a lot of P. falciparum
 Malaria is rarely found in heterozygous carriers of HbS (sickle cell trait)
 So in sickle cell in black africans, there’s a trade off between a risk of
fatal disease in the minority of homozygous recessive HbS, and
protection for more people who are heterozygous HbS carriers
 This is an example of a balanced genetic polymorphism
 In sickle cell trait, P. falciparum-infected RBCs adhere to the walls of
blood vessels using knobs that form as the parasites mature
o This sequesters infected cells in an area of decreased oxygen,
which facilitates sickling, potassium loss, and death of the
parasites
 Glucose-6-phosphate dehydrogenase deficiency (G6PD) – the RBC has less
ability to make NADPH through the pentose phosphate shunt, allowing easier
oxidative stress, which inhibits plasmodium growth
Chloroquine was once used to prevent malaria
 Chlorquine enters the parasite’s food vacuole, where RBC Hgb is degraded to
feed the parasite
 Normally, toxic heme released by this is detoxed and converted to harmless
malarial pigment called hemozoin
 Chloroquine blocks heme detoxification and kills plasmodium
 Chloroquine resistance happens by mutation of the vacuole membrane protein,
that causes chloroquine to be pumped out of the food vacuole
 This resistant mutation to P. falciparum is now widespread in most endemic
areas
 Current treatment is with malarone, coartem, quinine plus doxycycline, or
quinidine
 Mefloquine is a quinine derivative that can kill chloroquine-resistant strains as
well, but it is often toxic at treatment doses
 Despite this, mefloquine is a mainstay for chemoprophylaxis in travelers
to endemic areas
 Now there is even mefloquine resistance happening
 None of these meds work against liver hypnozoite stages though, which is only
done by P. vivax and P. ovale
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Use primaquine for these, but it’s more toxic and causes nausea,
vomiting, and diarrhea
Primaquine won’t work against P. falciparum or P. malariae
Babesia
o Another protozoa that infects RBCs, and causes fever on release
o Unlike malaria though, babsiosis is endemic in the US
o Babesia microti is the most common cause of babesiosis in the Us
o Babesia microti is endemic in the same areas as lyme disease, because B. microti and
borrelia burgdorferi ( bacteria that causes lyme disease) infect the same animal
reservoir, the white-footed mouse, and are transmitted to humans by the same deer
tick
o Symptoms of babesiosis are nonspecific, and include flu-like symptoms of fever, chills,
sweats, muscle aches, and fatigue
o Babesiosis usually happens in the summer, when the ticks are feeding
o So babesiosis is sometimes called the “summer flu”
o Illness is usually mild, but worse if there’s no spleen
o Giemsa stains are also used for babesia
o The mainstay for treatment of babesia is clindamycin plus quinine
Tissue protozoa:
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Toxoplasma gondii – causes toxoplasmosis, a common infection in humans
o Less than 1% infected though ever have the disease
o 3 syndromes caused by Toxoplasma gondii:
 A mononucleosis-like syndrome – but tests for EBV and CMV are negative
 A congenital infection of the fetus that is severe
 Infections of immunocompromised hosts, especially those with AIDS, that
involves the brain and heart
o People can get toxoplasmosis by eating inadequately cooked lamb meat with T. gondii
tissue cysts, or by ingesting the infectious oocyts found in the feces of cats
o Cats are critical for the propagation of T. gondii
 Where there are no cats, there is no toxoplasmosis
 Cats harbor the sexual cycle of toxoplasmosis gondii, and produce th
environmentally resistant infective oocysts in their feces
 Cats get them from eating other mammals, like rodents
o In nonfeline mammals, the toxoplasmosis parasites get to the small intestine and
penetrate the gut wall, invade the blood, and spread to the brain, heart, muscles, and
more
 In the first 4-6 weeks, an immune response is mounted, but it doesn’t eliminate
the toxoplasmosis, and instead lets them multiply to large #’s in cells, and enter
a dormant state, forming tissue cysts
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Cats get infected by ingesting animals tht have these tissue cysts in their
muscles and organs
 Toxoplasmosis gondii actually manipulates rat brains to make them attracted to
cat pheromones
o Humans also have spread of T. gondii from the intestines to the tissues, which may
cause transient symptoms in an immunocompetent person
 From then on, the infection remains inactive as a dead-end infection in the
tissues, unless the person becomes immunosuppressed some time later
o In the active phase of infection, T. gondii is found in macrophage
 It enters by active invasion, where it contacts the host cell membrane and forces
the parasite into a membrane bound vesicle, which has no proteins that would
be normally involved in endocytosis
 This vesicle then becomes invisible to the host cell, and won’t be targeted to a
lysosome
 This happens in nonactivated macrophage, but activated macrophage can
phagocytose T. gondii and kill it
o You diagnose T. gondii with elevated antibodies, especially IgM antibodies
o Most previously healthy people don’t need treatment for self-limited acute
toxoplasmosis
 Immunocompromised people might not develop antibodies to check for
 New neuro symptoms, and ring-enhancing lesions on imaging of the brain
should raise suspicion of nervous system toxoplasmosis
 In the brain, toxoplasmosis can cause inflammation, severe necrosis, tissue
damage, and death
 Since brain tests are risky, if they have symptoms and a positive brain scan, you
just assume they have brain toxoplasmosis, and give them sulfadiazine or
clindamycin
o T. gondii can be transmitted to a developing fetus if mom gets infected during
pregnancy in the first trimester
 Women with preexisting antibodies at the time of pregnancy (indicating prior
infection), have virtually no risk of producing a congenitally infected child
Leishmania:
o Cause lots of symptoms, from superficial ulcers to severe lesions of the liver, spleen, and
bone marrow, along with system signs like fever, weight loss, and anemia
o Superficial lesions are produced by leishmania species that grow better at lower
temperatures
o Leishmania that infect organs grow better at higher temperatures
o Leishmania are small protozoa that are flagellates with flagella
 The flagellum is connected to an organelle called the kinetoplast, which has its
own DNA
o Leishmania are transmitted by the bite of sand flies, mostly found in tropical parts of
the world
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Leishmaniasis in the US is rare, usually in travelers
Leishmaniasis reservoirs are rodents, dogs, and infected humans
Leishmania diseases include localized skin ulcers, mucocutaneous lesions called
espundia, disseminated cutaneous lishmaniasis, and disseminated visceral leishmaniasis
(kala azar)
o Leishmania use lipophosphoglycan on its surface binds to one of the complement
receptors on macrophage
 Phagocytosis then happens
 Once taken up into the phagocyte, leishmania differentiate into an amastigote
form with no flagella
 The amastigote is in the phagosome, but it’s resistant to lysosomal enzymes
 The amastigote also depends on the low pH of the phagolysosomes for the
uptake of nutrients
o Leishmoniasis is one of the most common causes of unexplained fevers in people with
AIDS
Trypanosome cruzi – causes Chagas disease in latin America
o Most infected people got the infection by a bite from an infected reduviid bug
(aka”kissing bug”)
 The bite may forma a chancre, or there may be swelling there
o Usually chagas disease is mild with just fever, but some cases are serious and fatal
o The complications of Chagas disease result from damage to nerves int eh GI,
conducting tissue in the heart, or the heart muscle
o Sudden death from cardiac arrhythmia is common in chagas disease
o Fibrosis is the hallmark of Chagas disease
o Treatment for early Chagas disease includes ifurtimox or benznidazole
Trypanosome brucei – causes African sleeping sickness, endemic in Africa
o It’s transmitted by the bite of infected tsetse flies
o T. brucei can do antigenic variation of its surface antigen, which is variable surface
glycoprotein
o Weeks to months after initial infection, the patient develops a systemic illness with
fever and swollen lymph nodes
o After several months or years, the T. brucei invade the CNS and infect the brain and
spinal fluid
o During months or years of chornic blood infection, patients unergo bouts of parasitemia
 During each bout, the parasite changes its dominant surface antigen, variable
surface glycoprotein
o Eflrnithine is the main drug to treat T. brucei