Blood Parasites

Question 1

Parasites

Answer 1

In the broad sense of the term, any pathogen is a “parasite” as it lives at the expense of the host. The more narrow meaning of the term “parasite” refers to pathogens that are eukaryotes, but not fungi.

Question 2

A large number of adults in the United States are infected with the protozoan ____.

Answer 2

A large number of adults in the United States are infected with the protozoan Toxoplasma gondii

Question 3

Protozoa

Answer 3

One-celled eukaryotes.

For protozoa that serve as parasites, transmission from one host to another usually depends on arthropod vectors.

An alternative strategy used by some protozoa is to alternate between two distinct forms: an active trophozoite form that grows and replicates by binary fission with the host, and a dormant, nonreplicating cyst form that is adapted for survival in various environmental extremes as it transits between hosts.

Question 4

Helminths of medical importance

Answer 4

Roundworms, flatworms (also called flukes) and tapeworms

Question 5

Malaria

Answer 5

Caused by five species of Plasmodium: P. falciparum, P. vivax, P. ovale, P. malariae and P. knowlesi. Blood parasites. Has a complex life cycle, resulting in cycles of fever, chills, and anemia.

48 hour cycle: P. vivax or P. ovale

72 hour cycle: P. malariae

Irregular: P. falciparum

Question 6

Plasmodium-mediated disease

Answer 6

Symptoms ~8-30 days after infection. Cycles of fever, chills, anemia, nausea, diarrhea, vomitting. Synchronized lysing of erythrocytes. Affects liver, then erythrocytes. Anemia results from erythrocyte lysis.

Question 7

Length of malaria cycle vs species

Answer 7

48 hour cycle: P. vivax or P. ovale

72 hour cycle: P. malariae

Irregular: P. falciparum

Question 8

Plasmodium life cycle

Answer 8

Question 9

Plasmodium-mediated damage (based on life cycle alone)

Answer 9

• Sporozoites are injected into the human bloodstream when infected mosquitoes bite and feed.
• Organisms enter hepatocytes within 30 minutes of injection (hepatocellular cycle)
• Merozoites are released from liver and infect erythrocytes
• After 2-3 days erythrocytes burst and produce new merozoites (erythrocytic cycle)
• A minority of the merozoites in the blood develop into forms capable of sexual reproduction (gametocytes)
• Gametocytes are taken up by biting mosquitoes, where they fuse in sexual reproduction
• Parasite develops in mosquito and spreads to salivary glands where they may produce new infections.

Question 10

Plasmodium-mediated damage (aside from life cycle)

Answer 10

• Coordinated erythrocyte lysis produces many DAMPs which activate production of IL-1 and TNF-α, resulting in systemic acute fever.
• Malaria may cause splenomegaly, and splenectomized patients have higher degrees of parasitemia and more severe infections
• P. falciparum invades erythrocytes of all ages
• P. falciparum causes the red blood cells to bind to the vascular endothelium, potentially resulting in ischemia (pfEMP-1 - ICAM-1)
• pfEMP-1 is encoded by var genes. Each genome contains ~60 var genes and there are over 30,000 total known. This makes it impossible for the immune system to consistently respond.
• P. vivax and P. ovale create hypnozoites in the liver, which serve as a dormant source of infection

Question 11

Relative virulence of Plasmodium species

Answer 11

Plasmodium falciparum is much more virulent than the other species

Question 12

Diagnosis of malaria

Answer 12

1. Giemsa-stained smear of peripheral blood (may even differentiate species)
2. Rapid antigen detection tests
3. PCR

Serologic testing is of little value, as acutely ill patients are ill 3-5 weeks before they develop an antibody response.

Question 13

Ring stage Plasmodium in erythrocytes

Answer 13

Question 14

Natural immunity to malaria is. . .

Answer 14

. . . imperfect. People in endemic areas have some resistance, but not complete resistance.

Question 15

Treatment of Malaria

Answer 15

Chloroquine was once the most widely used drug for antimalarial chemoprophylaxis and treatment. Unfortunately, chloroquine-resistant P. falciparum are now widespread in most of Southeast Asia, South America, and Africa.

Patients infected with chloroquineresistant P. falciparum can be treated with other agents, such as Malarone (a fixed combination of atovaquone and proguanil), Coartem (a fixed combination of artesunate and lumefantrine), quinine plus doxycycline, or quinidine.

None of the above are effective against the P. ovale and P. vivex hypnozoites, but primaquine is effective against dormant malaria, and is often given to prevent relapse.

Question 16

Recommended treatment of acute malaria?

Of dormant malaria?

Answer 16

Acute: Malarone

Dormant: Primaquine

Question 17

Prevention of Malaria

Answer 17

Mosquito nets, mosquito nets, mosquito nets

Plus insecticides and draining of stagnant water

Question 18

Babesia

Answer 18

• Babesia* species are protozoal parasites that cause illness by infecting red blood cells and generating fever on release. Unlike malaria, babesiosis is endemic in the United States. It occurs primarily in the Northeast and upper Midwest.
• Babesia microti* is the common cause of human babesiosis in the United States.

Question 19

Source of Babesia infection

Answer 19

Babesia is transmitted to humans by Ixodes ticks (which can also transmit Lyme disease). The animal reservoir for Babesia is the white footed mouse.

Human infection can also occur through blood transfusion and, rarely, through organ transplantation.

Humans are a dead-end host.

Question 20

Babesia-mediated disease

Answer 20

Babesiosis is difficult to recognize clinically because the illness it causes is nonspecific. Infected persons experience a flulike illness, with fever, chills, sweats, muscle aches, and fatigue.

Illness is usually mild, but more severe disease occurs in splenectomized patients. As in malaria, the spleen is thought to remove the Babesia-infected red blood cells from the circulation.

Question 21

Babesiosis in erythrocytes

Answer 21

Question 22

Treatment of Babesiosis

Answer 22

Babesia infections are treated with different chemotherapeutic agents than malaria: azithromycin and atovaquone or clindamycin plus quinine.

Question 23

Toxoplasma gondii

Answer 23

Disseminates widely in the human host and can be found in a variety of tissues. Usually very benign or completely asymptomatic, except in immunocompromised individuals. Specifically, occurs very frequently in AIDS or late stage HIV patients.

Question 24

Source of Toxoplasma infection

Answer 24

1. Eating inadequately cooked meat
2. Ingesting infectious oocytes found in cat feces

Question 25

___ are critical for the propagation of T. gondii

Answer 25

Cats are critical for the propagation of T. gondii

They are the definitive host, as mosquitoes are for malaria.

Question 26

Toxoplasmosis-mediated disease

Answer 26

3 distinct syndromes:

1. mononucleosis-like syndrome in which tests for the common viral agents of mononucleosis—Epstein-Barr virus and cytomegalovirus—are negative
2. Congenital infection that may have severe consequences if acquired in the first trimester of pregnancy. Chorioretinitis, which many infants develop early or many years after birth, is sometimes the only manifestation of congenital infection.
3. Infections in immunocompromised hosts (especially people with AIDS), often involving the brain or the heart

Question 27

Toxoplasma-mediated damage

Answer 27

• T. gondii spreads from the intestine to the tissues
• Early dissemination is when mononucleosis-like syndrome may occur
• Thereafter, the infection remains inactive as a latent infection in the tissues (particularly the brain) unless the person becomes immunosuppressed at some time in the future
• Immunosuppression, particularly lack of cell-mediated immunity, allows the parasite to proliferate and form expanding necrotic lesions.

Question 28

Diagnosis of Toxoplasmosis

Answer 28

• In the immunologically competent host, diagnosis is made by anti-toxoplasma IgM titer
• In immunocompromised patients, presence of multiple ring-enhancing lesions on a computerized tomography scan or magnetic resonance imaging should raise suspicion for toxoplasma
• Because most of the potential damage occurs in utero, treatment after the baby is born is usually too late. Therefore, some physicians screen women for anti-toxoplasma antibody when pregnancy is first detected.

Question 29

Treatment of Toxoplasmosis

Answer 29

• Most healthy people do not need any treatment for self-limited, acute toxoplasmosis
• AIDS patients with a suggestive history, positive brain scan, and serological evidence of prior toxoplasmic exposure (e.g., specific IgG antibody) are treated presumptively for cerebral toxoplasmosis. Lifesaving treatment is usually initiated with pyrimethamine plus sulfadiazine
• Women who seroconvert during pregnancy can be given treatment with spiramycin.

Question 30

Prevention of Toxoplasmosis

Answer 30

Women who are seronegative can be given preventative advice. This includes recommendations to avoid rare meats, to avoid handling cat litter and feces, and to wash their hands after contact with cats.

There is no vaccine.

Question 31

Chondroitin sulfate A

Answer 31

Placenta-specific vasculature protein which is bound by Pfemp1.

Of note, it is the only placenta-specific target for Pfemp1, so blocking it completely avoids the direct effects of malaria on the placenta wall.

Question 32

____ may induce premature delivery.

Answer 32

High levels of TNF-α may induce premature delivery.

Question 33

Memory antibodies against ____ drive enhanced immunity to malaria in subsequent pregnancies.

Answer 33

Memory antibodies against the condroitin sulfate A-specific Pfemp1 variant drive enhanced immunity to malaria in subsequent pregnancies.

Question 34

Definitive host

Answer 34

The host in which sexual reproduction of a parasite occurs

Question 35

Despite passing through ____, malaria has never been known to cause ____.

Answer 35

Despite passing through the liver, malaria has never been known to cause hepatic symptoms.

Question 36

“Maltese Cross” erythrocytes

Answer 36

Pathopneumonic for babesiosis. Specific and sensitive enough even to diagnose.