BLOOD AND TISSUE PROTOZOANS - MICRO {ST1}

1. BLOOD AND TISSUE PROTOZOANS - MICRO {ST1} BY RANJEET RAMAN

2. Malaria Humans are the only reservoir for the four Plasmodium species (falciparum, vivax, ovale, and ​malaria). These are all transmitted by the Anopheles mosquito. Mosquito bite transmits sporozoites, a few of which will invade hepatocytes. These replicate ​into thousands of merozoites, which go to bloodstream to infect RBC.

3. Vivax and ovale also have a hypnozoite liver stage where the parasite is dormant for months-years. RBCs burst, releasing around 20 merozoites that infect other RBC. A very tiny fraction of these ​sometimes become gametocytes that are infective for the next mosquito bite.

4. These ​mature, leaving creating sporozoites in the mosquito salivary glands for future infection. Disease is from the RBC infection, not the liver infection!

5. Classical symptoms of malaria are fever, splenomegaly, and anemia. Anemia comes from RBC lysis but also from sequestration of iron in heme crystals. Fevers, headache, and pain coincide with schizont rupture from RBCs.

6. P. falciparum In addition to fever, P. falciparum causes cerebral coma, dangerous anemia, lactic acidosis, ​hypoglycemia, acute renal failure, splenomegaly, and pregnancy complications. ​Falciparum infections are a medical emergency. This is because falciparum can invade RBCs of all ages, leading to huge parasitemia.

7. Hypoglycemia and lactic acidosis occurs because falciparum has no Kreb’s cycle, so it ​undergoes inefficient cytosolic glycolysis (not exactly the same as fermentation), where ​the end product is lactic acid.

8. Micro vascular sequestration is also a very important process. RBCs infected with ring-stage ​falciparum will transport attachment proteins to their surfaces and bind to endothelium. ​Mature parasites become sequestered in capillaries, and only immature parasites circulate.

9. This cytoadherence causes huge decreases in perfusion, oxygen sat, and metabolism. ​Interestingly, histopathology remains normal, with no signs of necrosis. ​The effects, such as coma, renal failure, pulmonary edema, and diarrhea are probably ​more cytokine mediated.

10. *Parasite burden does not correlate with peripheral parasitemia in P. falciparum due to this ​sequestration of mature forms! P. vivax and ovale Severe fever but death is rare because parasitemia is limited by the requirement that vivax can ​only invade reticulocytes. The Duffy blood group antigen is also required for invasion.

11. Vivax and ovale have a dormant stage in the liver – this stage is the hypnozoite. Innate Resistance to Malaria Infections Red cell polymorphisms are due to selective advantage of malaria on the heterozygote. Sickle cell: modified structure of the beta-globin chain Thalassemia: slowed rate of globin chain synthesis. Other conditions involve the RBC membrane or the Duffy blood group antigen.

12. Toxoplasma gondii – Toxoplasmosis A third of world population infected, but disease is rare. Transmission is by ingestion of cysts in ​undercooked muscle or vegetables. Cats are the definitive hosts, and they may excrete millions of infective oocytes, which persist in ​the soil and are ingested on meat. T. gondii invades all tissue types. Often seen as a cyst in muscle tissue, with tons of purple dots.

13. May cause congenital infections, eye problems, encephalitis, or even mononucleosis. Loss of immunity with HIV or organ transplant leads to multifocal necrosis in the brain and wide ​dissemination.

14. Leishmaniasis The vector is the sandfly Exists in humans as a non-flagellated obligate amastigotes inside ​reticuloendothelial cells. Disease is a result of leukocyte infection. Amastigotes are taken up in phagolysosome, but they thrive in low pH of the lysosome. Localized cutaneous ulcers are non-painful fleshy lesions with raised borders.

15. Mucocutaneous disease may cause destructive nasopharyngeal metastasis years later. Black fever is the visceral disease, characterized by massive hepatosplenomegaly. Like Toxoplasmosis, Leishmaniasis infects many but disease is rare.

16. African Trypanosomiasis – Sleeping Sickness The vector is the tsetse fly, which inoculates trypomastigotes that replicate extracellularly in the ​bloodstream. The protozoan is Trypanosoma brucei gambiense. They can be seen as ​ribonny extracellular parasites.

17. Disease includes fevers, insomnia, anemia, headache. Causes polyclonal activation of B cells ​with some autoantibodies and suppression of humoral immune function. ​May case enlarged occipital lymph nodes, and eventual invasion of the brain. Trypanosomes will show considerable antigenic variation.

18. American Trypanosomiasis – Chagas Disease The vector is the reduvid (kissing) bug, and the protozoan is Trypanosoma cruzi. Bug feces containing trypomastigotes are rubbed into bug bite wounds. Mature extracellularly. Chagoma is the inflammation at the bite site.

19. Followed by fever, lymphadenopathy, myocarditis. Followed by lots of organ inflammations and fibrosis. GI neurons are invaded, causing severe gastroparesis and intestinal enlargement.

20. PARASITIC NEMATODE INFECTIONS {ST1}

21. Most helminths do not multiply inside the definitive host. The major exception is Strongyloides. Distribution in the human population follows a negative binomial pattern. Most helminth infections evoke eosinophilia, elevated IgE and mast cell proliferation.

22. Protozoans generally don’t evoke eosinophilia, because it is generally a feature of ​helminths residing in tissues, especially during helminth migration or dying. ​Eosinophilia may arise before eggs or larvae can be detected by diagnostic procedures.

23. Enterobius vermicularis – Pinworm This is a nematode (roundworm) that deposits eggs in perianal area. Self-infection by scratching ​perianal area and touching mouth. Environmental surfaces may be contaminated. Larvae ​hatch in small intestine and mature in the colon.

24. Gravid females migrate nocturnally outside the anus to ovipositor on the skin. Pinworm is often asymptomatic. Perianal itching, anorexia, and abdominal pain.

25. Ancylostoma duodenale and Necator Americanus – Hookworm Both are nematodes. Eggs pass and hatch in the stool. Penetrate the skin of the foot, travel in ​veins to heart and then lungs. Penetrate alveoli, ascend bronchus, and are swallowed. ​Eventually settle in the lumen of the small intestine.

26. Attach to intestinal walls, causing some blood loss. Adults eliminated within two years. Causes anemia from blood loss, GI and metabolic symptoms, and is dangerous in pregnancy.

27. Ascaris lumbricoides – Ascaris Largest parasitic nematode. Lives in lumen of small intestine shedding huge loads of eggs. Ingested eggs invade intestinal mucosa, go through portal system to the lungs, travel up, and get ​swallowed. Settle in lumen of the small intestine. This is the most common human helminthic infection. May cause stunted growth, obstruction. Easy treatment with albendazole

28. Trichuris trichiura – Whipworm Ingested eggs hatch in the small intestine and migrate to the colon as adults. Can cause ​abdominal pain, diarrhea, growth retardation, and rectal prolapse.

29. Strongyloides stercoralis – Strongyloides Very complex lifecycle that alternates between free and parasitic cycles. Can autoinfect and multiply inside the host!! Can cause persistent infections for years. Filariform larvae penetrate skin, go to the lungs, and are swallowed to reach the small intestine.

30. Frequently asymptomatic, sometimes with diarrhea and rash. Look for larvae in the stool. Strongyloides may disseminate in immunosuppressed patients, and can be fatal. Very high host eosinophilia.

31. Trichinella spiralis – Trichinosis Acquired by eating meat containing Trichinella cysts. Often pig or bear meat. Larvae invade mucosa of the small intestine, then migrate to striated muscles, where it encysts. Intestinal invasion leads to diarrhea, cramping, vomiting.

32. Muscle invasion leads to facial edema, conjunctivitis, fever, splinter hemorrhages, myalgias, ​rash, and eosinophilia. Symptoms may last months. Treat with mebendazole plus steroids.

33. Toxocara cani – Toxocariasis or “larva migrans” Lifecycle occurs in dogs. Eggs start in infected puppies that release eggs, which we then contact ​in the soil or sandboxes. Larvae disseminate to liver, heart, lungs, brain, eyes.

34. Larvae don’t mature to adult stage in humans, so stool exam will have no eggs!! Lots of eosinophilia seen because of migration. Visceral larva migrans (VLM) occurs in young children, causing all kinds of disseminated ​problems and hypereosinophilia. Ocular larva migrans (OLM) occurs in young adults, causing ocular lesions but no eosinophilia ​or other visceral problems.

35. Filarial Nematode Infections Filariasis is an infection by roundworms that inhabit the lymphatics and subcutaneous ​tissue. Larvae are transmitted in insect bites. Females produce larvae, not just eggs. Most filariasis infections are asymptomatic. The rest are chronic, not acute infections. Lymphatic diseases are characterized by elephantiasis and hydroceles.

36. Infected individuals show strong Type2 immune rxns with high IgE and eosinophilia. Putatively immune individuals show strong Type1 immune rxns with activity against filarial ​antigens.

37. Wuchereria bancrofti and Brugia malayi Transmitted by mosquitoes. Microfilariae are sheathed. They travel in lymph and blood. Nocturnal periodicity! Causes lymphedema and elephantiasis. Especially in lower extremities and scrotum. Eosinophilia is seen.

38. Onchocerca volvulus – River blindness Transmitted by blackflies. Develops into adults in the subcutaneous tissue, creating ​subcutaneous nodes. Adults in these nodes can produce microfilariae for years ​which travel in lymphatics. Causes pruritis, depigmentation, onchocercomata (subcutaneous nodes), elephantiasis, and ​blindness. Urine is thick with lymph. This is called chyluria.

39. Chrysops silacea – Loa Loa Transmitted by flies. Adults reside in subcutaneous tissue. Might see in Peace Corp voluntary. Diurnal periodicity. Causes episodic edemas, often of the face (Calabar swellings) and subconjunctival ​migration of worms.