Malaria biology, pathogenesis and symptomatology.pptx

This is a presentation on malaria

1. Malaria; biology, pathogenesis and symptomatology Presenter: Mary Joseph Moderator: Prof Billy Ngasala

2. Outline Introduction morphology Life cycle Pathogenesis and symptomatology

3. Malaria Malaria is a tropical disease caused by heamoglobin digesting protozoans parasite known as Plasmodium spp. It is transmitted by blood sucking female anopheles mosquito Two host are involved, Human are intermediate host while mosquito are definitive host and vectors. There are for common plasmodium species that cause malaria to human; plasmodium falciparum, plasmodium malariae , plasmodium ovale , and plasmodium vivax . Plasmodium knowlesi , a plasmodium specie for monkey has been also found to cause malaria to human

4. Malaria cont … The plasmodium species reproduce both sexually and asexually, where by the sexual reproduction occurs in mosquito and asexual reproduction takes place in human. Some plasmodium species cause a non relapsing malaria( P.falciparum , P. malariae , and P. knowlesi ) and some causes a relapsing malaria( P. ovale , P. vivax ).

5. P. falciparum Found worldwide in tropical and subtropical areas. It is estimated to cause approximately 1 million people deathes every year, especially in Africa where this species predominates. Can cause severe anemia because it multiples rapidly in the blood, and can rapid destruction of RBCs, but also can cause cerebral malaria when infected red blood cells clog small blood vessels in the brain.

6. P. vivax Found mostly in Asia, Latin America, and in some parts of Africa. it is probably the most prevalent human malaria parasite. P. vivax has dormant liver stages (" hypnozoites ") that can activate and invade the blood ("relapse") several months or years after the infecting mosquito bite.

7. P. ovale Found mostly in Africa (especially West Africa) and the islands of the western Pacific. It is biologically and morphologically very similar to P. vivax . It has dormant liver stages (" hypnozoites ") that can activate and invade the blood ("relapse") several months or years after the infecting mosquito bite.

8. P. malariae It is found worldwide, rarely cause a life threatening infection. If untreated, P. malariae causes a long-lasting, chronic infection that in some cases can last a lifetime and can cause serious complications such as the nephrotic syndrome.

9. P. knowlesi Found throughout Southeast Asia as a natural pathogen of monkeys [long-tailed and pig-tailed macaques]. It has recently been shown to be a significant cause of zoonotic malaria in that region, particularly in Malaysia. P. knowlesi has a 24-hour replication cycle and so can rapidly progress from an uncomplicated to a severe infection; fatal cases have been reported.

10. Classification of Malaria parasites Kingdom: Protista Phylum: A picomplexa Class: Haematozoea Order: Haemosporida Family: Plasmodiidae Genus: Plasmodium Species: P. vivax , P. falciparum , P. malariae , P. ovale , P. knowlesi

11. M orphology Three morphologic forms in peripheral blood; Trophozoites schizont gametocytes.

12. Morphology cont … Plasimodium malariae Trophozoites have compact cytoplasm and a large chromatin dot. Occasional band forms and/or “basket” forms with coarse, dark-brown pigment can be seen. Troph . In thick film Troph in thin film band and basket form in thin film

13. Morphology cont … P. malariae schizont P. malariae schizonts have 6 to 12 merozoites with large nuclei, clustered around a mass of coarse, dark-brown pigment. Merozoites can occasionally be arranged as a rosette pattern Schizont in thick film schizont in thin film

14. Morphology cont … Gametocytes round to oval with scattered brown pigment, they may almost fill the infected red blood cell .

15. Morphology cont … Plasmodium falciparum Trophozoites; rings have delicate cytoplasm and one or two small chromatin dots. Infected RBCs is normal in size, multiple infection of RBCs is more common in P. falciparum than in other species. Occasional appliqué forms (rings appearing on the periphery of the RBC) can be present. Maurer’s clefts may also be present.

16. Morphology cont … Gametocytes; are crescent or sausage shaped. The chromatin is in a single mass (macrogamete) or diffuse (microgamete).

17. Morphology cont Schizonts ; are seldom seen in peripheral blood. Mature schizonts have 8 to 24 small merozoites; dark pigment, clumped in one mass

18. Morphology cont … Plasmidium ovale Trophozoites; Have sturdy cytoplasm, large chromatin dots, can be compact to slightly irregular. RBCs are normal or slightly enlarged round to oval sometimes may be fimbriated . Multiple infection to RBCs may occur. Schuffer’s dot may be visible

19. Morphology cont … Schizonts Have 6-14 merozoites with large nuclei, clustered around a mass ofdark brown pigments

20. Morphology cont … Gametocytes They are round to oval, may almost filling the infected RBC with more course brown pigments.

21. Morphology cont … P. Vivax Trophozoite ; amoeboid cytoplasm, large chromatin dots, and have fine, yellowish-brown pigment. Schüffner's dots appears more fine compared to those seen in P. ovale . RBCs normal or enlarged in size and may be distorted.

22. Morphology cont … Gametocytes; are round to oval with scattered brown pigment and may almost fill the RBC. Schüff-ner's dots appears more fine in comparison to those seen in P. ovale .

23. Morphology cont … Schizont ; large , have 12 to 24 merozoites, yellowish-brown, coalesced pigment, and may fill the RBC.

24. Life cycle of Malaria parasite Involves two hosts: humans & female Anopheles mosquitoes. The life cycle have two stages; sexual stage which occurs in the mosquito and asexual stage which occurs in human. In humans, the parasites g row and multiply first in the liver cells ( exoerythrocytic phase) and then in the red blood cells (erythrocytic phase). The infection to human is through penetration of sporozoite to the blood stream though a mosquito biting during feeding which then invade the liver parenchymal cells where they multiply and split( a process called schyzogony ) and release merozoitezoites .

25. Life cycle cont … Merozoites invade RBC where erythrocytic schyzogony occurs, releasing daughter parasites ("merozoites") that continue the cycle by invading other red cells. Once the parasite is in the red blood cells stage its where the symptoms of malaria starts to appear to the infected individual Some of the merozoites will form male and female gametocytes (macrogametes and microgametes) which are picked up by a female Anopheles mosquito during a blood meal.

26. Life cycle cont … In the mosquito, the male and female gametocytes mature and fertilization occurs in the gut of the mosquito to give rise to large number of sporozoites ( a process called sporogony ). Sporozoites invade the mosquito's salivary glands. When the Anopheles mosquito takes a blood meal on human , the sporozoites are injected with the mosquito's saliva and start another human infection cycle.

27. Life cycle cont …

28. Pathogenesis and symptomatology of Malaria Infection Malaria disease can be categorized as  uncomplicated  or  severe( complicated) malaria   malaria pathology is caused by products of erythrocytic schizogony and the host’s reactions to the parasite. The febrile paroxysms follow the completion of erythrocytic schizogony , when the mature schizont ruptures, releasing red cell fragments, merozoites, malarial pigment and other parasitic debris.

29. Pathoginesis cont …. Release of this products stimulate macrophages and polymorphs which phagocytose these products and release large quantities of Cytokines , leading to elevation of temperature. Tumour necrosis factor (TNF) and interleukin-l play pivotal role in the pathogenesis of malaria fever.

30. Pathogenesis cont ….. Malarial toxins Malaria parasite is reported to release a lipid molecule called glycosyl phosphatidyl inositol (GPI) Which is released during schizont rupture from its membrane protein. This stimulates macrophages to release pro-inflammatory cytokines, Tumour Necrosis Factor (TNF-alpha) & Interforon Gama (INF-δ) which are known to cause the malarial fever and symptoms of malaria . Cytokines upregulate the endothelial expression of vascular ligands for P. falciparum-infected erythrocytes, notably ICAM-1, and thus promote cytoadherence.

31. sequestration Infected RBCs containing late stage of parasite adhere to the endothelium of capillaries and venules (cytoadherence) to escape the splenic mechanism cytoadherence begins at approximately 12 h after merozoite invasion, and reaches 50% of maximum after 14–16 h. Distribution of sequestered erythrocytes varies markedly from vessel to vessel and organ to organ, possibly reflecting differences in the expression of endothelial receptors

32. A naemia Anaemia occurs in all types of malaria, but is most pronounced in P. falciparum infections The type of anaemia is haemolytic, normocytic, normochromic anaemia Anaemia is caused by the destruction of parasitized red cells as well as increased destruction of red cells possibly by autoimmune and decreased erythropoiesis.

33. S plenomegaly The spleen is invariably affected. may be enlarged and soft. Later , it becomes dark due to accumulated malarial pigment, diffuse cellular hyperplasia, dilated sinusoids and accumulation of macrophages accentuate the enlargement of spleen, which becomes hard due to fibrosis.

34. Symptomatology Uncomplicated malaria The cardinal symptom if fever, accompanied by Headache, Muscular ache, vague abdominal discomfort, diarrhea, nausea, vomiting, shivering, sweating, Lethargy, Lassitude and dysphoria often precede fever by up to 2 day. Severe malaria Cerebral malaria; impaired consciousness, Seizures, coma, Encephalopathy . Severe anemia due to hemolysis (destruction of the red blood cells Severe anemia due to hemolysis (destruction of the red blood cells)

35. S ymptomatology Acute respiratory distress syndrome (ARDS), an inflammatory reaction in the lungs that inhibits oxygen exchange, which may occur even after the parasite counts have decreased in response to treatment Hemoglobinuria (hemoglobin in the urine) due to hemolysis Acute kidney injury Metabolic acidosis (excessive acidity in the blood and tissue fluids), often in association with hypoglycemia

36. Other manifestation of Malaria Malaria in pregnancy May cause severe disease to a mother, increased incidence of anaemia reduction in birth weight or premature delivery. Nephrotic syndrome (a chronic, severe kidney disease) can result from chronic or repeated infections with  P. malariae . Neurologic defects may occasionally persist following cerebral malaria, especially in children. Patient may present with trouble in movements (ataxia), palsies, speech difficulties, deafness, and blindness.

37. Other manifestation of Malaria Hyper reactive malarial splenomegaly (also called “ tropical splenomegaly syndrome”; occurs rarely and  is attributed to an abnormal immune response to repeated malarial infections May present with; very enlarged spleen and liver. abnormal immunologic findings. anemia individual become susceptibility to other infections (such as skin or respiratory infections).

38. Reference Textbook of Medical Parasitology, 6 th edition by Panker CK, (2007); Chpt 3.; Pg 65-95. Diagnostic Medical Parasitology, 5 th edition by Lynne SG (2007); chapt 5; Pg 582-586. 3. Erber WN. P. falciparum. Aust J Med Sci. 2000;21(1):56. 4. Pengertian A. Malaria ( Plasmodium malariae ). 2015; 5. Capillary A, Blood B, Giemsa W-. P. Ovale . DPDx Lab Identif Parasites Public Heal Concern [Internet]. 2014;1–4. Available from: https://www.medbox.org/laboratory-diagnosis-of-malaria-plasmodium-ovale/preview?q=malaria+diagnostics 6. Thakor HG. Laboratory Diagnosis of Malaria. J Indian Med Assoc. 2000;98(10):623–7.