Protozoan and Helminthic Diseases of the Cardiovascular and Lymphatic Systems

Chagas Disease (American Trypanosomiasis)

Chagas disease is caused by the protozoan parasite Trypanosoma cruzi and transmitted via the reduviid bug.

Learning Objectives

Describe the life cycle of Trypanosoma cruzi

Key Takeaways

Key Points

  • Chagas disease is prevalent in areas with reduviid bugs such as Central and South America.
  • Chagas disease is transmitted via a vector, the reduviid bug, which becomes infected when it bites an already-infected individual.
  • The life cycle of Trypanosoma cruzi requires two hosts, the reduviid bug and the human or animal host.

Key Terms

  • zoonotic: of or relating to zoonosis, the transmission of an infectious disease between species.

Chagas disease, also known as American trypanosomiasis, is caused by the parasite Trypanosoma cruzi. It is transmitted to humans via the reduviid bug (the “kissing bugs”), and is therefore characterized as a zoonotic disease.

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Trypanasoma cruzi

Chagas disease is similar to African sleeping sickness which is caused by the African trypanosome. The risk factors for Chagas disease include living where reduviid bugs live, including areas of Central and South America. In addition, it is possible to obtain Chagas via blood transfusion from an individual with the active disease.

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Reduviid bug: In Chagas-endemic areas, the main mode of transmission is through an insect vector called a triatomine or reduviid bug.The bugs emerge at night, when the inhabitants are sleeping. Because they tend to feed on people’s faces, triatomine bugs are also known as “kissing bugs.” After they bite and ingest blood, they defecate on the person. Triatomines pass T. cruzi parasites (called trypomastigotes) in feces left near the site of the bite wound.

The reduviid bug itself becomes infected by feeding on the blood of an already-infected person or animal. The bugs are nocturnal, emerge at night and typically feed on an individual’s face. The bug then proceeds to defecate on the person, passing Trypanosoma cruzi parasites in its feces in posterior station infection. These parasites surround the bite wound and, when the bite is scratched, the parasites are able to pass into the host. The reduviid bud often bites the tender skin around the eyes, leaving a swollen bump called a chagoma or Ramona’s sign.

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Romaña’s sign: The most recognized marker of acute Chagas disease is called Romaña’s sign, which includes swelling of the eyelids on the side of the face near the bite wound or where the bug feces were deposited or accidentally rubbed into the eye.

At this specific stage, the parasites are referred to as trypomastigotes, and these invade the host cells and differentiate into intracellular amastigotes where they continue to multiply by binary fission. These amastigotes then differentiate into trypomastigotes which circulate into the bloodstream. At this time, if the infected individual is re-bitten by a reduviid bug, the cycle will start again.

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Lifecycle of Trypanasoma cruzi: Chagas disease can be characterized by two phases: acute and chronic. The acute phase is characterized by mild symptoms which include fever, swelling of an eye or area surrounding the insect bite. However, the acute phase will enter remission and then, over time, additional symptoms will develop that include: constipation, gastrointestinal issues, heart failure, abdominal pain and difficulties swallowing.

Chagas disease can be characterized by two phases: acute and chronic. The acute phase is presents with mild symptoms which include: fever, swelling of an eye and/or the area surrounding the insect bite.

The acute phase will then enter remission and, over time, additional symptoms will develop that include: constipation, gastrointestinal issues, heart failure, abdominal pain and difficulties swallowing. It can sometime take upwards of 20 years from the time of infection for these later heart and digestive issues to present. American trypanosomiasis causes megacolon and megaesophagus and an enlarged heart in pediatric patients and is very serious.

Toxoplasmosis

Toxoplasmosis is a parasitic disease caused by the protozoan Toxoplasma gondii and its life cycle mandates a definitive host which are cats.

Learning Objectives

Compare and contrast: acute and latent toxoplasmosis and outline the life cycle of the protazoan that causes it

Key Takeaways

Key Points

  • Cats are the definitive hosts for Toxoplasma gondii and are the primary source of infection to humans.
  • Toxoplasmosis can occur in either acute, latent or cutaneous forms.
  • Toxoplasmosis is found worldwide and can be transmitted by eating undercooked meat of animals which may contain cysts, ingesting contaminated food or water, transplacentally or from coming in contact with infected cat feces.

Key Terms

  • definitive host: a host in which the parasite reaches maturity and, if possible, reproduces sexually
  • axillae: The armpit
  • transplacental: Through or across the placenta

Overview

Toxoplasmosis is an infection caused by the parasite Toxoplasma gondii. Toxoplasmosis is found in humans worldwide, but the definitive hosts are cats. Humans may become infected as a result of infected blood transfusions, organ transplants, ingesting contaminated soil, raw or undercooked meat, and most commonly from the careless handling of cat litter, which can lead to accidental ingestion of the parasite. Toxoplasmosis can also be passed from an infected mother to her baby via the placenta (transplacentally). Symptoms that may occur from toxplasmosis include: enlarged lymph nodes, headache, fever, muscle pain, and sore throat. Individuals with immunocompromised or weakened systems display more severe symptoms, such as: confusion, fever, headache, blurred vision and seizures. The three categories of toxoplasmosis include acute, latent, and cutaneous toxoplasmosis.

Symptoms

Acute toxoplasmosis is characterized by swollen lymph nodes found in the neck or under the chin, followed by the axillae, and the groin area. Enlarged lymph nodes will occur at different times after the initial infection. Latent toxoplasmosis is characterized by the formation of cysts in both the nervous and muscle tissue due to the bradyzoite form of the parasite. Often times, individuals infected with latent toxoplasmosis do not present with symptoms, as the infection enters a latent phase. In individuals with cutaneous toxoplasmosis, skin lesions will occur due to the tachyzoite form of the parasite and its presence in the epidermis.

Hosts, Life Cycle

The known definitive hosts for Toxoplasma gondii are members of family Felidae (domestic cats and their relatives). In the life cycle of this parasite, unsporulated oocysts are shed in the cat’s feces. The cat will shed large numbers of these cysts over a short period of time. The oocysts will then take 1-5 days to sporulate in the environment and become infective. The intermediate hosts in nature (including birds and rodents) become infected after ingesting contaminated soil, water, or plant material. The oocysts, upon ingestion, will transform into tachyzoites, which will localize in the neural and muscle tissue. After localizing to these sites, they will develop into tissue cyst bradyzoites. Cats, can become infected after consuming intermediate hosts that are infected with tissue cysts or by ingesting sporulated oocysts.

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Toxoplasmosis Life Cycle: Overview of the life cycle of Toxoplasmosis godii.

Malaria

Malaria is a mosquito-borne infectious disease that affects humans and other animals caused by various species of the protist Plasmodium.

Learning Objectives

Reconstruct the route of transmission and life cycle for Plasmodium species that cause malaria and describe its symptoms

Key Takeaways

Key Points

  • The five common species of Plasmodium that cause malaria include: Plasmodium falciparum, Plasmodium vivax, Plasmodium ovale, Plasmodium malariae and Plasmodium knowlesi.
  • Mosquitoes transmit the protists by injecting sporozoites into the bloodstream of humans.
  • The sporozoites injected into the bloodstream, travel to the liver where they multiply into merozoites, rupture the liver cells, and then return to the bloodstream.
  • A mosquito, upon feeding off an already infected individual, will carry the protists and become infectious.
  • The symptoms of malaria can present in a cyclic manner.

Key Terms

  • merozoites: the organisms formed by multiple fission of a sporozoite within the body of the host.
  • antigen: A substance that induces an immune response, usually foreign.
  • sporozoites: Any of the minute active bodies into which a sporozoan divides just before it infects a new host cell.
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The malaria plasmodium: Malaria is transmitted to people and animals by mosquitoes. Malarial sporozoites develop inside oocysts and are released in large numbers into the hemocoel of Anopheles stephensi mosquitoes. This false-colored electron micrograph shows a sporozoite migrating through the cytoplasm of midgut epithelia.

Malaria is a parasitic disease that is caused by the bite of an infected Anopheles mosquito. Malaria can be transmitted from mother to baby and by blood transfusions. The Anopheles mosquito transmits the parasites, called sporozoites, upon biting the hosts, into the bloodstream to the liver, where the parasites continue their life cycle. In the liver, the parasites mature and release another form called merozoites, which enter the bloodstream and infect the red blood cells. In the red blood cells, they develop into ring forms called trophozoites and schizonts that in turn, produce further merozoites. Upon infection of the red blood cells, the parasite is able to multiply within the cell, break open and continue infecting additional red blood cells. The symptoms occur in a cyclical manner every 48-72 hours. Malaria is characterized by the development of symptoms that include high fevers, shaking chills, flu-like symptoms, and anemia. The symptoms that persist due to parasitic infection are a result of the release of merozoites into the bloodstream, destruction of the red blood cells and the free circulation of large amounts of hemoglobin in the red blood cells due to disruption.

The five types of malaria parasites include species of Plasmodium. The fives species include: Plasmodium falciparum, Plasmodium vivax, Plasmodium ovale, Plasmodium malariae, and Plasmodium knowlesi. Plasmodium falciparum is responsible for the majority of deaths caused by infection and Plasmodium vivax, ovale and malariae cause a milder form of malaria. The species, Plasmodium knowlesi, commonly causes malaria in macaques but can also cause severe infections in humans.

Malaria is common in temperate climates and the Centers for Disease Control and Prevention (CDC) estimates 300-500 million cases each year. In addition, it is estimated that 1 million people die from it each year as well. Malaria is typically diagnosed by microscopic examination of blood or with antigen-based rapid diagnostic tests. Disease transmission can be reduced by preventing mosquito bites through the use of mosquito nets and insect repellents. However, the mosquitoes which transmit malaria have begun to develop resistance to insecticides and the parasite itself has developed resistance to commonly used antibiotics. As a result of increased resistance, it is extremely difficult to contain the spread of this disease.

Leishmaniasis

Leishmaniasis is caused by the protozoan parasite Leishmania and presents itself in two forms: cutaneous or visceral leishmaniasis.

Learning Objectives

Outline the life cycle of Leishmania and distinguish between cutaneous or viseral leishmaniasis

Key Takeaways

Key Points

  • Leishmaniasis is a vector-borne disease and is transmitted by the sand fly.
  • Cutaneous leishmaniasis is the most common form of leishmaniasis and symptoms include skin sores.
  • Visceral leishmaniasis is more severe and is characterized by the migration of parasites to the vital organs and tissues.

Key Terms

  • visceral: of or relating to the viscera – the internal organs of the body
  • cutaneous: of, relating to, existing on, or affecting the exterior skin; especially the cutis
  • phagocytosis: the process by which a cell incorporates foreign particles intracellularly.

Leishmaniasis is a disease transmitted by the bite of a female sandfly. There various types of leishmaniasis that exist including cutaneous leishmaniasis, systemic, or visceral leishmaniasis. Cutaneous leishmaniasis is characterized by infection of the skin and mucous membranes. The symptoms include skin sores which present at the site of the sandfly bite. In addition, cutaneous leishmaniasis includes breathing difficulty, stuffy nose, runny nose, nose bleeds, swallowing difficulty and ulcers in the mouth, tongue, gums, lips, nose, and inner nose. Systemic or visceral leishmaniasis present as an infection of the entire body. There is a delay of symptoms, ranging from 2-8 months post bite, and the effects on the immune system can result in deadly complications. The parasites damage the immune system by targeting the disease-fighting cells. Symptoms present much more quickly in children and include a cough, diarrhea, fever, and vomiting. In adults, there is fatigue, weakness, loss of appetite, abdominal pain, night sweats, fever, weight loss, and changes in the color and texture of the skin. In combination, cutaneous and visceral leishmaniasis are caused by more than 20 different leishmanial species.

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Leishmaniasis: A Phlebotomus papatasi sand fly that transmits one type of leishmaniasis, next to an image of Leishmania sp. promastigotes from culture. This is the stage of the parasite that occurs inside the mid-gut of the sand fly.

Leishmaniasis is vector-borne because it is transmitted via a bite from a sandfly. The sandflies that cause leishmaniasis are infected by an obligate intracellular protozoa of the genus Leishmania. The species of Leishmania that can cause leishmaniasis include: L. donovani complex with 2 species (L. donovani, L. infantum, also known as L. chagasi); the L. mexicana complex with 3 main species (L. mexicana, L. amazonensis, and L. venezuelensis); L. tropica; L. major; L. aethiopica; and the subgenus Viannia with 4 main species (L. (V.) braziliensis, L. (V.) guyanensis, L. (V.) panamensis, and L. (V.) peruviana). These various species are indistinguishable via morphology but can be identified using advanced techniques such as isoenzyme analysis.

Leishmaniasis is transmitted by the bite of infected female phlebotomine sandflies which can transmit the infection Leishmania. The sandflies inject the infective stage, metacyclic promastigotes, during blood meals. Metacyclic promastigotes that reach the puncture wound are phagocytized by macrophages and transform into amastigotes. Amastigotes multiply in infected cells and affect different tissues, depending in part on which Leishmania species is involved. These differing tissue specificities cause the differing clinical manifestations of the various forms of leishmaniasis. Sandflies become infected during blood meals on infected hosts when they ingest macrophages infected with amastigotes. In the sandfly’s midgut, the parasites differentiate into promastigotes, which multiply, differentiate into metacyclic promastigotes, and migrate to the proboscis.

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Leishmaniasis life cycle: Leishmaniasis is a vector-borne disease and is transmitted by the sand fly.

Babesiosis

Babesiosis is a malaria-like parasitic disease caused by infection with Babesia, a parasite transmitted to human hosts by ticks.

Learning Objectives

Outline the life cycle of the Babesia microti parasite that causes babesiosis

Key Takeaways

Key Points

  • Babesia, the parasite, is capable of undergoing both sexual and asexual reproduction in its life cycle.
  • A majority of individuals infected with babesiosis are asymptomatic but severe cases display malaria-like symptoms which include high fevers, chills, shakes, and hemolytic anemia.
  • A definitive characteristic of Babesia infection is the formation of a “Maltese Cross” structure within the erythrocytes that represents the asexual budding of four attached merozoites.

Key Terms

  • piroplasms: a protozoan parasite of the phylum Apicomplexa.
  • sporozoite: any of the minute active bodies into which a sporozoan divides just before it infects a new host cell
  • hemolytic: producing hemolysis; destroying red blood cells

Babesiosis is a malaria-like parasitic disease caused by Babesia. Babesia is a genus of protozoal piroplasms which are characterized by their ability to divide by binary fission. Also, protozoal piroplasms are sporozoan parasites, and so they possess both sexual and asexual phases. The piroplasm is categorized under Phylum Apicomplexa and specifically, Babesia, is a parasite transmitted via a tick vector. Many of the cases of Babesia infection are asymptomatic but can include mild fevers and diarrhea. The more severe cases are plagued with high fevers, shaking chills, and severe anemia, similar to symptoms seen in individuals infected with malaria. If the disease progresses without treatment and it is severe, the infected individual can suffer from organ failure and adult respiratory distress syndrome. Recently, there has been an increase in babesiosis diagnosis due to an increase in the number of individuals with immunodeficiencies coming into contact with ticks.

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Babesia parasites: Other hemoprotozoan parasites such as these Babesia sp. resemble Plasmodium falciparum organisms. Though developmentally the Babesia spp. organisms resemble Plasmodium falciparum, these parasites present several distinguishing features: they vary more in shape and in size; and they do not produce pigment.

The life cycle of Babesia parasites is characterized by their ability to undergo reproduction in the erythrocytes. These parasites, within the red blood cells, form a distinctive structure called a “Maltese Cross” that is composed of four attached merozoites undergoing asexual budding. This asexual process results in hemolytic anemia. The Babesia microti life cycle includes two hosts, a rodent, primarily the white-footed mouse, and a tick.

During a blood meal, the tick introduces sporozoites into the mouse host. The sporozoites enter the erythrocytes and undergo asexual reproduction as previously mentioned. In the blood, the parasites will then differentiate into male and female gametes. The definitive host, the tick, will then ingest both types of gametes (upon another blood meal). The gametes will unite and undergo a sporogonic cycle resulting in sporozoite. The humans play a role in this cycle if they are bitten by an infected tick. The tick will introduce the sporozoites and the cycle will proceed. Diagnosis of babesiosis is performed using a Giemsa-test for parasitic identification. The “Maltese Cross” is observed on blood films and both serological testing for antibodies and PCR testing for Babesia from the peripheral blood is performed.

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The life cycle of Babesia parasites: Babesia is capable of undergoing both sexual and asexual reproduction in its life cycle. Ticks transmit the human form of Babesiosis, so it often presents with other tick-borne illnesses such as Lyme disease.

Schistosomiasis

Schistosomiasis is a parasitic disease caused by various species of trematodes or “flukes,” which are of the genus Schistosoma.

Learning Objectives

Outline the life cycle of the trematodes of the genus Schistosoma that cause schistosoomiasis

Key Takeaways

Key Points

  • For parasites categorized as schistosomes, the snail is the intermediary agent between the mammalian hosts.
  • Schistosomiasis is common in countries that lack the facilities to maintain proper water supplies and sanitation facilities. These supplies and facilities are often exposed to contaminated water that contains infected snails.
  • Individuals infected with schistosomiasis display chronic illness that can result in the damage of internal organs and in children, affects target growth and cognitive development.

Key Terms

  • hepatopancreas: An organ of the digestive tract of arthropods and fish which provides the function which in mammals is provided separately by the liver and pancreas.

Schistosomiasis is a parasitic disease caused by various species of trematodes or “flukes,” which are of the genus Schistosoma. For parasites categorized as schistosomes, the snail is the intermediary agent between the mammalian hosts.

Schistosomiasis is common in countries that lack the facilities to maintain proper water supplies and sanitation facilities. These supplies and facilities are often exposed to contaminated water that contains infected snails. Individuals infected with schistosomiasis display chronic illness that can result in the damage of internal organs and in children, targets growth and cognitive development. Children will often acquire the disease by swimming or playing in contaminated water. Upon contact with contaminated water, the parasitic larvae can penetrate the skin and mature within the organ tissues.

The life cycle of the various human schistosomes is similar. The parasitic eggs are released into the environment from already-infected individuals and hatch on contact with water, releasing free-swimming miracidia. These infect freshwater snails by penetrating their skin. The site of penetration will promote the transformation of the miracidium into a primary sporocyst. This contains germ cells which will divide to produce secondary sporocysts. In turn, these migrate to the snails’ hepatopancreas and the germ cells, now present within the secondary sporocysts, will divide to form thousands of new parasites called cercariae. These are the larvae capable of infecting mammals.

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Schistosome Life Cycle: Overview of Schistosome generalized life cycle.

Interestingly, the cercariae are released from the snail host in a circadian rhythm and depend on ambient temperature and light. Penetration of the human skin occurs after the cercariae have attached to and explored the skin. The parasite secretes enzymes that break down the skin’s protein to enable penetration of the cercarial head through the skin. As the cercaria penetrates the skin, it transforms into a migrating schistosomulum stage.

The various species which can infect humans include:

  • Schistosoma mansoni, Schistosoma intercalatum: cause intestinal schistosomiasis
  • Schistosoma haematobium: causes urinary schistosomiasis
  • Schistosoma japonicum, Schistosoma mekongi: cause Asian intestinal schistosomiasis
  • Avian schistosomiasis species: cause swimmer’s itch and clam digger itch

Swimmer’s Itch

Swimmer’s itch is a result of an immune reaction in response to the penetration of the skin by a schistosome.

Learning Objectives

Outline the general life cycle of the Schistosomatidae parasite that causes schistosome cercarial dermatitis

Key Takeaways

Key Points

  • Swimmer’s itch is commonly referred to as lake itch, duck itch, cercarial dermatitis and Schistosome cercarial dermatitis.
  • The cercaria, the larvae stage of the parasite, will accidentally penetrate the skin of a human host and die within the skin. The cercaria cannot continue the life cycle in a human and requires its normal host, a waterfowl.
  • The penetration of the skin by the cercaria result in an inflammatory immune reaction that causes itchy spots and raised papules in humans.

Key Terms

  • swimmer’s itch: Swimmer’s itch, also known as lake itch, duck itch, cercarial dermatitis, and Schistosome cercarial dermatitis, is a short-term, immune reaction occurring in the skin of humans that have been infected by water-borne schistosomatidae.
  • papules: A small, inflammatory, irritated spot on skin; similar in appearance to a pimple, without containing pus.
  • cercaria: The parasitic larva of trematodes; its tail disappears when adult.

Swimmer’s itch is a condition often referred to as lake itch, duck itch, cercarial dermatitis and Schistosome cercarial dermatitis. It is caused by an immune response that is activated upon the entry of a water-borne flatworm parasite named schistosomatidae into the skin. The schistosomatidae results in an immune reaction in the skin that results in itchy, raised papules that occur within hours of infection.

There are numerous types of flatworm parasites within the family Schistosomatidae that can cause swimmer’s itch. The schistosomatidae which are responsible for swimmer’s itch include the genera Trichobilharzia and Gigantobilharzia. A species that is often implicated in cases of cercarial dermatitis is Austrobilharzia variglandis. The hosts of this species are ducks and the snail is the intermediate host for this species.

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Life cycle of schistosomes: An overview of the life cycle of a schistosome and how they can cause swimmer’s itch in humans.

The life cycle of these parasites is characterized by their use of both freshwater snails and vertebrates as hosts. More specifically, waterfowl are used as the vertebrate host. During the life stage of these parasites, the larvae of the parasite, cercaria, exit the water snails and can accidentally come into contact with the skin of a swimmer. Upon contact with the skin of the swimmer, the cercaria will penetrate the skin and immediately die in the skin. Interestingly, the cercaria are unable to survive within a human host and cause infection. The symptoms and reactions exhibited in individuals diagnosed with swimmer’s itch are a result of the dead cercaria larvae.

If indeed the cercaria encounter a water bird, their normal host, the cercaria will penetrate the skin of the birds and migrate to the blood vessels to complete the cycle. For completion of the cycle, adult worms will form in the blood vessels and produce eggs which are passed in the feces. The eggs, upon exposure to water, will hatch into a miracidium that is ciliated. This form in the life cycle infects the snail intermediate host. In turn, the cercaria which are responsible for swimmer’s itch are produced.