BLOOD AND TISSUE PROTOZOONS

1. BLOOD AND TISSUEPROTOZOONS PLASMODIUM TRYPANASOMA BABESIA Doç.Dr.Hrisi BAHAR

2. The Malarias:PLASMODIUMSPlasmodium falciparumPlasmodium vivaxPlasmodium malariaePlasmodium ovale PLASMODIUM SPECIES CAUSES “MALARIAS” IN HUMAN ►Plasmodium falciparum ►Plasmodium vivax ►Plasmodium malariae ►Plasmodium ovale

3. PLASMODIUMS ►The malaria parasite exhibits a complex life cycle involving an insect vector (mosquito) and a vertebrate host (human). ►Four Plasmodium species infect humans. ►All four species exhibit a similar life cycle with only minor variations.

4. PLASMODIUMS 1*The infection is initiated whensporozoitesareinjected with the saliva of a feeding mosquito. Sporozoites are carried by the circulatory system to the liver and invade hepatocytes 2*The intracellular parasite undergoes an asexual replication known asexoerythrocyticschizogonywithin the hepatocyte

5. PLASMODIUMS 3*Exoerythrocytic schizogony activates the production ofmerozoiteswhich are released into the bloodstream 4*Merozoitesinvade erythrocytes and undergo a trophic period in which the parasite enlarges 5*The early trophozoite is often referred to as'ring form' because of its morphology.

6. PLASMODIUM Ring form Ring form Plasmodium vivax Plasmodium malaria

7. Scanning electron micrograph of Plasmodium-infected red blood cells. One cell has burst open, releasing merozoites

8. PLASMODIUM ►Trophozoiteenlargement is accompanied by an active metabolism including the ingestion of host cytoplasm and the proteolysis of hemoglobin into amino acids. ►The end of the trophic period is manifested by multiple rounds of nuclear division without cytokinesis resulting aschizont

9. PLASMODIUM ►A proportion of the liver-stage parasites from P. vivax and P. ovale go through a dormant period instead of immediately undergoing asexual replication ►These hypnozoiteswill reactivate several weeks to months (or years) after the primary infection and are responsible for relapses.

10. PLASMODIUM ►The merozoites from the mature schizont are released following rupture of the infected erythrocyte. ►Invasion of erythrocytes reinitiates another round of the blood-stage replicative cycle

11. Life cycle Life cycle

12. PLASMODIUM ►The blood stage is responsible for the pathology associated with malaria ►The intermittent fever paroxyms are due to the synchronous lysis of the infected erythrocytes

13. PLASMODIUM ►P.malariaeexhibits a72hour periodicity, whereas the other three species exhibit48hour cycles for the fever. ►P. falciparum often exhibits a continuous fever rather than the periodic paroxyms. P.falciparum also is responsible for more morbidity and mortality than the other species

14. PLASMODIUM ►This increase virulence is due in part to the higher levels of parasitemia associated with P. falciparum infections. In addition, more complications are associated with P. falciparum because of the sequestration of the trophozoite- and schizont-infected erythrocytes in the deep tissues

15. PLASMODIUM ► As an alternative to the asexual replicative cycle, the parasite can differentiate into sexual forms known as macro- or microgametocytes ►The gametocytes are large parasites which fill up the erythrocyte, but only contain one nucleus. ► Ingestionof gametocytes by the mosquito vector induces gametogenesis and escape from the host Erythrocyte.

16. PLASMODIUM ►Microgametes, formed by a process known as exflagellation , are flagellated forms which will fertilize the macrogamete leading to a zygote . ► The zygote develops into a motile ookinete which penetrates the gut epithelial cells and develops into an oocyst

17. PLASMODIUM ►The oocyst undergoes multiple rounds of asexual replication resulting in the production ofsporozoites. ►Rupture of the mature oocyst releases the sporozoitesinto the body cavity of the mosquito The sporozoites migrate to and invade thesalivary glands, thus completing the life cycle.

18. PLASMODIUM In summary, malaria parasites undergothree distinct asexual replicative stages 1-Exoerythrocytic schizogony 2-Blood stage schizogony 3- Sporogony

19. General Clinical Manifestationof “Malaria” ►Infection is characterized by acute febrile attacks (malaria paroxysms) due to blood stage(not liver stage or gametocytes) ►Manifestations and severity of the infection depend on species and host status, immunity, general health,nutritional state, genetics.

20. General Clinical Manifestationof “Malaria” ►Recrudescences or relapses can occur over months or years and can develop severe complications.(especially P. falciparum)

22. PATHOGENESIS OF “MALARIA” Primary attack ►Infected erythrocyte rupture products of schizont, stimulate the release of cytokines (TNF)  paroxysm (shiver, fever, sweat)

23. PATHOGENESIS OF “MALARIA Relapse ► It is a recurrence that taken place after complete initial clearing of the erythrocytic infection and implies reinvation of the blood stream by merozoites from activated hypnozoites in liver.

24. PATHOGENESIS OF “MALARIA Recrudescence ► It is a recurrence of symptoms in a patient whose blood stream infection has previously been at such a low level as not to be clinically demonstrable or cause symptoms.

25. Complications Of “MALARİA” ►Anemia • Hemolysis of infected erythrocytes • Hypersplenism • Autoimmunization of uninfected erythrocytes • TNF- ► Splenomegaly: ► Malarious nephrosis ► Cerebral malaria

26. Diagnosis of “Malaria” ►1.Parasite; Species; Density *Thin blood films (species identification) *Thick blood films

27. Diagnosis of “Malaria” ►2Immuno-diagnosis *Specific antibody detection*Antigen detection *Specific DNA or RNA detection

28. Treatment 1.Treatment by classes of antimalarial drugs ►1) Blood schizonticides (quinine; chloroquine; artemisinin; mefloquine; sulfadoxin-pyrimethamine) -Effect on erythrocytic stage, use for acute attack.

29. Treatment ►2)Tissue schizonticides (Primaquine) -Effect on the stages in liver (including hypnozoite), use for prevent relapse (radical cure) of P.v or P.o malaria

30. Choice of drugs • 1)Treatment of vivax, malariae, ovale and chloroquine-sensitive falciparum malaria: chloroquine • 2)Radical cure of vivax or ovale malaria: chloroquine + primaquine • 3)Treatment of chloriquine-resistant falciparum malaria: artemisinin or mefloquine or quinine

31. Transmission and prevention ► Factors of transmission Suitable species of anopheles (60 species are considered to be vectors of malaria, major vectors in China: A. sinensis, A. minimus)

32. Transmission and prevention Prevention: Breaking the human-mosquito-human cycle • 1)Control of the source of infection by chemotherapy • 2)Control of transmission route: residual insecticides, avoidance of infected mosquitoes

33. Transmission and prevention • 3) ChemoproplylaxisTaking suppressive drugs, beginning one week before travel to endemic area and continuing until 6 weeks after return • 4) Malaria vaccines

34. TRYPANASOMA ►Trypanosomes infect a variety of hosts and cause various diseases, including the fatal diseaseSLEEPING SICNESSin humans. These deadly parasites mostly live in the blood and tissue fluids but can also inhabit intracellular locations in the host's body as well.

35. “Trypanasoma”

36. Life cycle ► < Infection occurs when infected metacyclic trypomastigotes enter the body through wound openings or mucous membranes. ► < The trypomatigotes enter various cells, differentiate into amastigotes and multiply intracellularly.

37. Life cycle ► < The amastigotes differentiate into trypomastigotes which are then released back into the bloodstream. ► < The life cycle is continued when a reduviid bug feeds on an infected person and ingests trypomastigotes in the blood meal.

38. Life cycle

39. TRYPANASOMA ►Human African Trypanosomiasis, also known as sleeping sickness, is a vector-borne parasitic disease. ► The parasites concerned are protozoa belonging to the Trypanosoma Genus. ► They are transmitted to humans by tsetse fly (Glossina Genus) bites which have acquired their infection from human beings or from animals harbouring the human pathogenic parasites.

40. tsetse fly Glossina brevipalpis

41. TRYPANASOMA ►Sleeping sickness occurs only in sub-SaharanAfrica in regions where there are tsetse flies thatcan transmit the disease. ► For reasons that are so far unexplained, there are many regions where tsetse flies are found, but sleeping sickness is not.

42. TRYPANASOMA ► Sleeping sicknessgenerally occurs in remote rural areas where health systems are weak or non-existent. The disease spreads in poor settings. Displacement of populations, war and poverty are important factors leading to increased transmission. ► The disease develops in areas whose size can range from a village to an entire region. Within a given area, the intensity of the disease can vary from one village to the next

43. TRYPANASOMA Human African Trypanosomiasis takes two forms, depending on the parasite involved. 1.form ►Trypanosoma brucei gambiense (T.b.g.) is found in west and central Africa. This form represents more than 90% of reported cases of sleeping sickness and causes a chronic infection. ►Aperson can be infected for months or even years without major signs or symptoms of the disease. When symptoms do emerge, the patient is often already in an advanced disease stage when the central nervous system is affected.

44. TRYPANASOMA 2.Form ►Trypanosoma brucei rhodesiense(T.b.r.) is found in eastern and southern Africa. This form represents less than 10% of reported cases and causes an acute infection. First signs and symptoms are observed after a few months or weeks. The disease develops rapidly and invades the central nervous system.

45. TRYPANASOMA Another form of trypanosomiasis occurs in 15 Central and South American countries. It is known as : American Trypanosomiasis or “Chagas disease”. The causal organism is a different species from those causing the African form of the disease.

46. Symptoms of “Sleeping Sicness” The disease is transmitted through the bite of an infected tsetse fly. At first the trypanosomes multiply in subcutaneous tissues, blood and lymph. In time, the parasites cross the blood-brain barrier to infect the central nervous system. The process can take years.

47. Symptoms of “Sleeping Sicness” ► The first stage of the disease, known as a “haemolymphatic phase”, entails bouts of fever, headaches, joint pains and itching. ► The second stage, known as the “neurological phase”, begins when the parasite crosses the blood-brain barrier and invades the central nervous system .

48. Symptoms of “Sleeping Sicness ►In general this is when the signs and symptoms of the disease appear: confusion, sensory disturbances and poor coordination. Disturbance of the sleep cycle, which gives the disease its name, is an important feature of the second stage of the disease. ►Without treatment, sleeping sickness is fatal.

49. Diagnosis Diagnosis must be made as early as possible and before the neurological stage in order to avoid complicated, difficult and risky treatment procedures. Diagnosis follows a three-step pathway ► Screening ► Diagnostic confirmation, ► Staging.

50. Diagnosis ► ► Diagnostic confirmation then relies on the finding of trypanosomes in the blood, lymph nodes, or cerebrospinal fluid (CSF). Unfortunately, it is estimated that 20 to 30% of patients are missed by the standard parasitological techniques