Protozoa are unicellular eukaryotes.
Amoebas move and feed by extending pseudopods, which are temporary extensions of the cytoplasm.
Entamoeba histolytica
Acquired as cysts in fresh water. Organisms that are acquired as cysts in fresh water are ECG –> Entamoeba, Cryptosporidium, Giardia.
Causes bloody diarrhea + liver abscesses, usually in patient who’s traveled outside the United States to Mexico or third-world country. I’ve seen one NBME Q where the latter was described as a “cystic lesion” on CT, even though it’s not a cyst (such as with Echinococcus granulosus, a tapeworm that causes hydatid cyst disease).
Can cause flask-shaped ulcers of the small bowel.
Demonstrates erythrophagocytosis (ingestion of RBCs). This is mentioned in an NBME Q.
NBME Q gives patient who traveled abroad + has bloody diarrhea + has abscess seen in the liver on CT + they ask for next best step in diagnosis –> answer = antigen testing for E. histolytica. Not difficult.
Treated with metronidazole + iodoquinol.
Acanthamoeba
Causes keratitis (inflammation of the cornea) and encephalitis.
Naegleria fowleri
Found in contaminated fresh water sources, i.e., lakes, hot springs, fountains, and sometimes drinking water.
Causes rapidly progressive meningoencephalitis and death within 1-2 weeks in nearly 100% of patients.
Enters through the cribriform plate in patients who have water enter their nose through diving, splashing, or deliberate washing of their sinuses. Does not cause infection if merely ingested.
This is the organism you see in the news once every 6 months as “brain-eating amoeba” that causes death in someone who swam in a lake.
Giardia lamblia
Acquired as cysts in fresh water. Organisms that are acquired as cysts in fresh water are ECG –> Entamoeba, Cryptosporidium, Giardia.
Causes steatorrhea (fatty stool), which can be described as extremely foul-smelling stool that floats. The patient can also have bloating.
There is one NBME Q for Giardia where they say the patient has foul-smelling watery diarrhea and bloating, which is audacious, since Giardia causes steatorrhea, but the “foul-smelling” and “bloating” point toward steatorrhea nevertheless.
The diarrhea is malabsorptive, where the patient can acquire nutritional and fat-soluble vitamin deficiencies.
Has two phases during its life cycle: trophozoite (left image), which is the actively reproducing, motile (with 8 flagella), and infective phase, and the cyst (right image), which is the dormant, non-infective stage. Both images are exceedingly HY spot-diagnoses for USMLE.
Patients with IgA deficiency are at increased risk of Giardia infection. Sometimes Hx of Giardia infection is mentioned in IgA deficiency questions.
Treat with metronidazole.
Trichomonas vaginalis
Causes trichomoniasis.
Presents as yellow-green discharge. Can cause “strawberry cervix,” or punctate hemorrhages on the cervix. If they don’t say this, they can sometimes say yellow-green discharge + a vaginal canal that is erythematous.
Flagellated protozoan. Diagnosed via visualization on wet mount.
Treat with metronidazole for patient and partner (high rate of reinfection).
Trypanosoma cruzi
Causes Chagas disease, aka American trypanosomiasis.
Spread by Reduviid bug. It is aka “kissing bug” because of its usually soft, painless bite.
Can cause Romaña sign, which is palpebral (eyelid) swelling 1-2 weeks after infection. This occurs when T. cruzi-containing feces from the Reduviid bug are rubbed into the eye. That is, the bite need not occur on or near the eye; the feces can be transferred from a bite elsewhere to the eye.
Can cause dilated cardiomyopathy, achalasia, and toxic megacolon.
Treated often with nifurtimox and benznidazole.
Trypanosoma brucei
Causes African sleeping sickness, aka African trypanosomiasis.
Spread by Tsetse fly.
Presents as daytime sleepiness and nighttime insomnia.
Treated often with suramin and melarsoprol.
Leishmania donovani
Causes Leishmaniasis.
Spread by the Phlebotomus sand fly.
USMLE likes the Middle East as location where it is prevalent. An NBME Q mentions a guy who went to Iraq.
Can cause skin ulceration at bite site (cutaneous leishmaniasis).
It can also cause visceral leishmaniasis (aka kala-azar), which can lead to pancytopenia and hepatosplenomegaly.
Treated often with sodium stibogluconate.
Sporozoans have a spore-forming phase and are distinguished by the presence of an apical complex at one end of the cell, which is used for invading host cells.
Plasmodium spp.
Causes malaria. Presents as flu-like illness with the development of hemolysis and varying fever patterns. P. falciparum causes hypoglycemia and cerebral malaria, which is more fatal.
Transmitted to humans by the Anopheles mosquito in regions of the world such as Africa, South America, and Asia.
Life cycle:
The Anopheles mosquito injects the sporozoite form of malaria into the blood. The sporozoites travel to the liver and mature into schizonts within hepatocytes, which undergo asexual reproduction to produce merozoites. A single schizont will contain many merozoites. This phase within the liver is called the hepatic, or exo-erythrocytic stage (I’ve seen this on NBME). The schizonts containing merozoites are then released into the blood.
Merozoites then invade RBCs (erythrocytic phase). Once inside the RBC, the merozoites mature into ring-shaped trophozoites, followed by new schizonts containing new merozoites.
Then the RBCs periodically burst, causing fever patterns. Trophozoites do not develop prior to the schizonts in the liver. So in short, the Anopheles mosquito injects Plasmodium into the host, then:
Hepatic (exo-erythrocytic) stage: sporozoite –> schizont –> merozoites –> leave liver.
Erythrocytic stage: merozoite –> ring-shaped trophozoite –> schizont –> merozoites –> burst RBC (causes fever).
As mentioned above, Plasmodium falciparum is the most severe type and causes cerebral malaria (neurologic deficits, seizures, headache), with greatest chance of death. The fever pattern is variable.
USMLE wants you to know that patients with P. falciparum can get hypoglycemia due to increased consumption of glucose by the organism. This is an answer on one of the NBME exams, where they give a simple vignette of malaria and then ask what is most likely to be seen in this patient, and the answer is hypoglycemia. Strikes students as weird, but it’s on the NBME.
Chloroquine can be given as prophylaxis, which inhibits malarial heme polymerase. However, some regions have high levels of chloroquine resistance, so mefloquine can be given instead. If they tell you a patient was given chloroquine and develops malaria anyway, the answer USMLE wants is “pharmacologic resistance”; the wrong answer is “non-compliance with medication.”
P. vivax and ovale cause tertian fever (every 48 hours; or every 3rd day). They form hypnozoites within the liver, which is a latent form. This is one of the highest yield details regarding malaria, where they will say a patient with the disease was treated successfully, but then months later has a resurfacing of symptoms.
Patients with P. vivax and ovale must receive primaquine, which kills hypozoites. I’ve seen the USMLE ask this numerous ways. They can ask for primaquine as the answer straight up. They can ask why primaquine is given for P. vivax and ovale, where the answer is “kills hypnozoites.” I’ve also seen “kills the exo-erythrocytic stage.”
P. malariae causes a more mild form of malaria and a quartan fever (every 72 hours; or every 4th day).
P. knowlesi is found predominantly in southeast Asia and causes a quotidian (daily) fever.
Malaria is diagnosed with thick and thin blood smears. This is asked on NBME, where “Plasmodium antigen testing” is wrong answer.
Toxoplasma gondii
Classically acquired from contact with infected cats, or via consumption of pork.
Toxoplasmosis presents as one or more ring-enhancing lesions on CT of the head. Can be in the context of seizures and/or miscellaneous neurologic symptoms as as a result of the CNS infection.
Patient need not be immunocompromised, but HIV patients with CD4 count <100 are at greater risk.
Prophylaxis is trimethoprim/sulfamethoxazole (TMP/SMX), which is the same as that for Pneumocystis jirovecii at a CD4 count of 200. So if a patient with a CD4 count of, e.g., 47, commenced TMP/SMX at CD4 count of 200 + has a seizure + ring-enhancing lesion, you know the diagnosis is not Toxo, since he/she is already on prophylaxis. The diagnosis in this case is primary CNS lymphoma (HY for AIDS under CD4 count of 100).
Treatment for Toxo is sulfadiazine + pyrimethamine. This is asked on a 2CK form, where they list both TMP/SMX and sulfadiazine + pyrimethamine; the latter is correct.
Congenital Toxo in neonates presents as a triad of: 1) hydrocephalus, 2) chorioretinitis, and 3) intracranial calcifications.
Cryptosporidium parvum
Acquired as cysts in fresh water. Organisms that are acquired as cysts in fresh water are ECG –> Entamoeba, Cryptosporidium, Giardia.
Causes watery diarrhea in person who goes overseas to third-world country (e.g., Mexico).
Diarrhea is self-limiting in immunocompetent persons –> Tx = supportive care.
Chronic diarrhea can occur in immunocompromised (e.g., HIV) –> Tx = nitazoxanide.
Appears as acid-fast cysts (same stain as TB).
Babesia
Spread by Ixodes tick, same as Lyme disease (Borrelia burgdorferi), Ehrlichia, and Anaplasma.
Causes malaria-like hemolytic disease in patient who never left the United States. In contrast, if the patient left the United States and went to (usually) Africa, the answer is malaria, not Babesia.
Can cause a ring-form on blood smear similar to malaria.
What the USMLE will do is tell you patient has fever + hemolytic disease of some kind + never left the US + show you above image; they will list both malaria and babesiosis as answers –> answer = babesia. Even though you’re aware malaria can also produce a similar-appearing ring-form, since the patient never left the US, you know it can’t be malaria. Conversely, if they show you ring-form and tell you patient recently went to Africa, you know it’s malaria, not babesia.
You also need to know Babesia can cause a maltese cross within RBCs:
