1. BLOOD AND TISSUE PROTOZOONS
PLASMODIUM
TRYPANASOMA
BABESIA
Doç.Dr.Hrisi BAHAR
Doç.Dr.Hrisi BAHAR

2. PLASMODIUM SPECIES CAUSES
The Malarias: PLASMODIUMS Plasmodium falciparum Plasmodium vivax Plasmodium malariae Plasmodium 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 when sporozoites are injected 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 as exoerythrocytic schizogony within the hepatocyte

5. PLASMODIUMS
3*Exoerythrocytic schizogony activates the production of merozoites which are released into the bloodstream
4*Merozoites invade 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
Scanning electron micrograph of Plasmodium-infected red blood cells. One cell has burst open, releasing merozoites

8. PLASMODIUM
► Trophozoite enlargement 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 a schizont

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 hypnozoites will 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
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.malariae exhibits a 72 hour periodicity, whereas the other three species exhibit 48 hour 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 of sporozoites .
► Rupture of the mature oocyst releases the sporozoites into the body cavity of the mosquito The sporozoites migrate to and invade the salivary glands, thus completing the life cycle.

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

19. General Clinical Manifestation of “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 Manifestation of “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”
► 2 Immuno-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
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) Chemoproplylaxis Taking 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 disease SLEEPING SICNESS in 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 sickness generally 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.
► A person 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

51. Treatment First stage treatments
Pentamidine: discovered in 1941, used for the treatment of the first stage of T.b. gambiense sleeping sickness.
Suramin: discovered in 1921, used for the treatment of the first stage of T.b. rhodesiense.

52. Treatment Second stage treatments
Melarsoprol: discovered in 1949, it is used in both forms of infection.
Eflornithine: this molecule, less toxic than melarsoprol, was registered in It is only effective against T.b. gambiense.

53. BABESIA
► Babesia is a protozoan parasite of the blood that causes a hemolytic disease known as Babesiosis.
► Babesia microti and Babesia divergens are the two species to most frequently infect humans

54. BABESIA SP ► There are >100 specicies of this intracellular
parasite.
► Babesia microti is the predominant human pathogen,
endemic to the Midwest.
► 10-20% of adults are seropositive in endemic areas
► Natural parasite reservoir is rodents
► Carried by the hard-bodied Ixodes Deer tick.
► Also carries agents for Lyme Disease, and
Ehrlichoisis.
► Can also be transferred transplacentally and through
blood transfusion.

55. Babesia in erythrocyts
Presence of 4 daughter merozoites in a tetrad .
Never seen in malaria.

56. Clinical presentation
► Ranges from asymptomatic infection to fatal illness (rare)
► No direct correlation between parasitemia and severity.
► More severe infection tends to occur in immunnocompromised, elderly, and the very young.

57. Clinical presentation
► The extreme end of the spectrum is often described as a malaria-like infection; symptoms may include malaise, chills, mylagia, anemia, fatigue, and fever .
Some cases also described emesis,
night sweats, weight loss, and hematuria.

58. Life cycle
► The trophozoite is very similar to the ring form of the Plasmodium species
► The organism (sporozoite) is transmitted by a tick and enters the red cell where it undergoes mitosis and the organisms (merozoite) are released to infect other red cells. Ticks acquire the organism during feeding on an infected individual. In the tick, the organism divides sexually in the gut and migrates into the salivary gland

60. Special Case – Splenectomy
► Illness appears suddenly, with hemoglobinuria as the presenting symptom followed by jaundice due to severe hemolysis.
► Parasitemia can reach 80% of RBCs
► Can be a medical emergency.
► In the most severe cases, patients develop a shock-like picture, with renal failure and pulmonary edema.
► Chronic disease with many relapses over months to years may occur if not treated.

61. Co-Infection
► It is estimated from serologic surveys that as many as 13% of Lyme disease patients in babesia-endemic areas are coinfected with B. microti
► The initial symptoms of both babesiosis and Lyme disease overlap significantly.
► Like babesiosis, Lyme disease also presents with nonspecific symptoms of fever,fatigue, and other flu-like symptoms.
► Patients coinfected with B. microti and B. burgdorferi experience more severe symptoms, but does not increase the duration of Babesia parisitemia.
► Doxycycline will not kill Babesia.

62. Diagnosis history of exposure. used .
► Diagnosis is based on clinical suspicion and
history of exposure.
► Thick and thin smears remain most clinically
used .
► Various PCR detection assays are available
for detection of B microtic and other species.
► Indirect fluorescent antibody test can also be
used as a confirmatory test.
► Can have false negatives (HIV) or false pos
(autoimmune)

63. Treatment
► Current treatment is Quinine plus Clindamycin
► 72% receiving quinine and clindamycin had side effects attributed to the drugs—diarrhea, tinnitus, or vertigo
► 15% receiving atovaquone plus azithromycin experienced side effects (usually diarrhea or rash).
► For severe cases (asplenic) with high levels of parasitemia, RBC exchange transfusions may also be necessary.