2) Malaria.pptxyffhgfhgfhgfhgfhgfhgfhgfh

uygjhg

1. Name is derived from Italian Mal’ aria or bad air Malaria is a mosquito-borne infectious disease of caused by parasitic protozoan of the genus Plasmodium . the disease is transmitted by a bite from an infected female Anopheles mosquito In humans, the parasites multiply in liver and infect the RBCs.

2. Landmarks in the History of Malaria 1740: Disease named malaria- Sir H Walpole 1820: Quinine isolated from cinchona bark- Indonesia 1880: Alphonse Laveran recognized & identified parasite in unstained Blood film—Nobel prize 1884: Patric Manson confirmed mosquito as a vector. 1898: Ronald Ross described the complete cycle of parasite in mosquito in Calcutta.

3. EPIDEMIOLOGY (KEY AFFECTED AREAS) WHO. World Malaria Report 20 10 Estimated 300-500 million clinical cases each year Approximately 2.5 million die each year

4. Malaria is an infectious disease caused by plasmodium species. Transmission of this parasite to human is by blood sucking bite of female anopheles mosquito of various species. ANOPHELES MOSQUITO CAUSATIVE AGENTS OF MALARIA

5. SPECIES TYPES OF MALARIA Plasmodium falciparum Malignant tertian malaria Plasmodium vivax Benign tertian malaria Plasmodium malariae Benign quartan malaria Plasmodium ovale Benign tertian malaria Out of the four species PLASMODIUM VIVAX and PLASMODIUM FALCIPARUM are the most common. Plasmodium species which infect humans

6. PLASMODIUM FALCIPARUM Malaria caused by P. falciparum is known as malignant tertian or pernicious malaria . The specific name ‘ falciparum ’ is derived from the characteristic sickle-shape of the gametocytes . DISTRIBUTION : Found mainly in tropical, sub- tropical, Africa, South America and Asia. PLASMODIUM FALCIPARUM

7. INCUBATION PERIOD : 12 days RBC CYCLE : 48 hrs or continuous MALARIAL PIGMENT : Dark , brown or blackish, one or two solid blocks DRUG RESISTANCE : Yes Length of sexual cycle : 9 – 10 days Length of asexual cycle : 36 - 48 hrs

8. Why P. falciparum is most highly pathogenic ?? This species infects all RBCs, resulting in prominent anemia. Its changes the RBC surface which causes endothelial adherence with decreased microcirculation and cerebral malaria.

9. PLASMODIUM VIVAX Malaria caused by P. vivax is vivax malaria or Benign tertian malaria. DISTRIBUTION : Prevalent in tropical and sub tropical countries like Asia and America. The species of P. vivax contains several sub species. Some are : Plasmodium vivax multinucleatum Plasmodium vivax hybernans PLASMODIUM VIVAX

10. INCUBATION PERIOD : 14 days RBC CYCLE : 44 – 48 hrs MALARIAL PIGMENT : Yellowish, brown, fine granules. DRUG RESISTANCE : No Length of sexual cycle : 8 – 9 days Length of asexual cycle : 48 hrs

11. PLASMODIUM MALARIAE Malaria caused by P. malariae is known as Benign quartan malaria or malariae malaria. It infects only senescent red cells. DISTRIBUTION : It is prevalent in tropical Africa and accounts for upto 25% of Plasmodium infection. PLASMODIUM MALARIAE

12. INCUBATION PERIOD : 30 days RBC CYCLE : 72 hrs MALARIAL PIGMENT : Dark, brown, coarse granules. DRUG RESISTANCE : No

13. PLASMODIUM OVALE Malaria caused by Plasmodium ovale is Benign tertian malaria. It may infect only reticulocytes . (<2 % of the RBC ) DISTRIBUTION : It is mainly found in West Africa where it is responsible for upto 10% of malarial infection. PLASMODIUM OVALE

14. INCUBATION PERIOD : 14 days RBC CYCLE : 48 hrs MALARIAL PIGMENT :Dark , yellowish, brown, coarse granules. DRUG RESISTANCE : No

15. Life Cycle of Malarial Parasite

16. Requires 2 hosts to complete it’s life cycle. Human acts as the intermediate host . Female anopheles mosquito acts as the vector and the definitive host.

17. Life cycle in Human Life cycle starts when an infected mosquito bites a human. Sporozoite – infective form of the parasite, elongated and spindle shaped. Present in salivary glands of the infected mosquito. Sporozoites are introduced to the blood stream during the blood meal. C onsists with several stages Pre – erythrocytic Schizogony Erythrocytic Schizogony Gametogony Exo – erythrocytic Schizogony

18. Pre – erythrocytic Schizogony Blood is infected with sporozoites about 30 minutes after the mosquito bite The sporozoites are eaten by macrophages or enter the liver cells where they multiply – pre- erythrocytic schizogony Elongated and spindle shaped sporozoites become round in shape. Undergo multiple nuclear division and develop in to merozoites. 20,000 – 50,000 merozoites. After compleion of the cycle liver cells rupture and release merozoites in to the blood stream

19. P. vivax and P. ovale sporozoites form resting stage in the liver called hypnozoites 1* The sporozoite is infective stage. 2* There are two kinds of sporozoites, tachy-sporozoite and brady-sporozoite 3* When the brady-sporozoites get into the liver cells , they undergo dormancy and called hypnozoites

20. Erythrocytic Schizogony Merozoites released from ruptured liver cells penetrates RBC. Pass through stages of trophozoite, schizont and merozoite. 6- 24 merozoites in a RBC (depends on the species of the parasite) RBCs rupture and release merozoites. Merozoites attacks healthy RBCs and continue their multiplication.

21. Erythrocytic phase stages of parasite in RBC Trophozoites are early stages with ring form the youngest Tropohozoite nucleus and cytoplasm divide forming a schizont Segmentation of schizont’s nucleus and cytoplasm forms merozoites Schizogeny complete when schizont ruptures, releasing merozoites into blood stream, causing fever These are asexual forms

22. Erythrocytic phase stages of parasite in RBC Merozoites invade other RBCs and schizongeny is repeated Parasite feed on Hb—Hb does not metabolized completely Excess protein, iron porphyrin and hematin left after Hb metabolism----malarial pigment Parasite density increases until host’s immune response slows it down Merozoites may develop into gametocytes, the sexual forms of the parasite

23. Gametogony Some merozoites develop in to male and female gametocytes. Known as microgametocytes and macrogametocytes respectively. Develop in the RBCs of the capillaries of the internal organs such as spleen and bonemarrow. Microgametocytes – Smaller in size, large nucleus, light blue stained cytoplasm Macrogametocytes – Larger in size, small and compact nucleus, deep blue stained cytoplasm

24. Exoerythrocytic schizogony (tissue phase) Resembles the preerythrocytic cycle. Some sporozoites do not undergo asexual multiplication but enter into a dormant stage /form (resting phase) and known as hypnozoites. After some time (usually upto 2 years) these dormant forms (latent stage) reactivates and capable of developing into to becom e merozoites . These merozoites attack red blood cells and are responsible for relapse of malaria. Exo-erythrocytic schizogony is absent in P. falciparum , therefore, relapses do not occur in malaria caused by P. falciparum .

25. Relapses in malaria It is renewed clinical manifestation or parasitaemia and may result from the following: Persistence of blood infection in which the surviving population of erythrocytic forms are increased. This is known as recrudescence and is a feature of P. falciparum infection. It may occur upto 1 year. Persistence of hypnozoite forms in the liver in which preythrocytic schizogony commences again. This is known as recurrence or true relapse and is a feature of P. vivax and P. ovale infections. In these cases, there is no erythrocytic schizogony in the latent period.

26. Relapses in malaria P. vivax and P. ovale hypnozoites remain dormant for months They develop and undergo pre- erythrocytic schizogony The Schizont rupture, releasing merozoites and produce clinical relapse

27. Life cycle in mosquito Male and female gametocytes enter in to the female anopheles mosquito during a blood meal from an infected human. In the mid gut of the mosquito each microgametocytes develops into 4 to 8 micro gametes by the process of exflagellation. one macrogametocyte forms only one macrogamete and does not show any exflagellation. Macrogamete and microgamete fuse together to form a zygote which develops in to ookinete. O o kinete develops into oocyst. Oosyct matures and develops into thousand s of sporozoites.

28. On or about 10 th day of infection, oocyst ruptures, releasing sporozoites in the body cavity of the mosquito. Sporozoites distributed through circulating fluid into various organs and tissues of mosquito (except ovaries). But have special predilection towards the salivary glands and ultimately reach the maximum concentration in the ducts. The mosquito at this stage is capable of transmitting infection to man and a single bite is sufficient for this purpose.

29. Exo- erythrocytic (hepatic) cycle Sporozoites Mosquito Salivary Gland Malaria Life Cycle Life Cycle Gametocytes Oocyst Erythrocytic Cycle Zygote Schizogony Sporogony Hypnozoites (for P. vivax and P. ovale )

30. Malaria Transmission Cycle Parasite undergoes sexual reproduction in the mosquito Some merozoites differentiate into male or female gametocytes Erythrocytic Cycle: Merozoites infect red blood cells to form Schizont Dormant liver stages (hypnozoites) of P. vivax and P. ovale Exo-erythrocytic (hepatic) Cycle: Spororzoites infect liver cells and develop into Schizont, which release merozoites into the blood MOSQUITO HUMAN Spororzoites injected into human host during blood meal Parasites mature in mosquito midgut and migrate to salivary glands

31. Pre-patent period – interval between date of infection and detection of parasites in peripheral blood Incubation period – time between infection and first appearance of clinical symptoms

32. Schizogenic periodicity and fever patterns Schizogenic periodicity is length of asexual erythrocytic phase 48 hours in P.f . , P.v . , and P.o . (tertian) 72 hours in P.m . ( quartan ) The febrile paroxysm synchronises with the erythrocytic schizogony of the malarial parasite. With 48 hour cycle of erythrocytic schizogony the fever recurs every third day (P. vivax ), with a 72 hour cycle the fever recurs every fourth day (P. malariae ).

33. Malaria the disease Malaria tertian: 48h between fevers ( P. vivax and ovale ) Malaria quartan : 72h between fevers ( P. malariae ) Malaria tropica : irregular high fever (P. falciparum )

34. Types of Infections Recrudescence Occurrence of clinical malaria caused by Plasmodium persisting in circulation at a subclinical level following a previous attack ( P.f., P.m. ) Relapse reactivation of hypnozoites forms of parasite in liver, separate from previous infection with same species ( P.v. and P.o. ) Recurrence or reinfection exo-erythrocytic forms infect erythrocytes, separate from previous infection (all species) Can not always differentiate recrudescence from reinfection

35. Malaria l Pathogenesis

36. PATHOGENESIS Malaria infection develops via two phases: L iver (exoerythrocytic phase ), E rythrocytes (erythrocytic phase).

37. HEPATIC PHASE S porozoites from mosquito's saliva enter the bloodstream M igrate to the liver where they infect hepatocytes, multiplying asexually for a period of 8–30 days . After a dormant period organisms differentiate to yield merozoites Rupture host cells, escape into the blood and infect red blood cells

38. P.vivax and P.ovale form hypnozoites in hepatocytes remains dormant, then reactivates and form merozoites causing late relapse in P.vivax malaria.

39. ERYTHROCYTIC PHASE Binds to RBCS Hydrolyze Hb by enzymes Trophozoites formed(single chromatin) Formation of schizonts Lysis of RBCs

40. Gametocytes are formed by parasites in RBCs which infect mosquito when it bites infected person

41. P arasite is protected from body's  immune system  because it resides within the liver and blood cells invisible to immune surveillance.

42. CEREBRAL MALARIA P. falciparum infect RBCs leading to parasitic burden and anemia RBCs clump together(rosette)and stick to endothelial cells of blood vessel(sequestration)

43. Sequestered red blood cells can breach the blood–brain barrier Proteins like PfEMP1 forms knob Stimulates production of cytokines TNF,IL-1 Induce fever,suppreses RBCs production, stimulate Nitric oxide production(tissue damage )

44. IMPACT OF SICKLE CELL TRAIT Sickle cell trait causes cell to distort into curved shape The molecule is ineffective in releasing oxygen. Reduces the frequency with which malaria parasites complete their life cycle in the cell.

45. CLINICAL FEATURES OF MALARIA

46. The signs and symptoms of malaria typically begin 8–25 days following infection. Symptoms may occur later in those who have taken antimalarial medications as prevention . Initial manifestations of the disease—common to all malaria species—are similar to  flu-like symptoms and can resemble other conditions such as   septicemia, gastroenteritis and viral diseases

47. Febrile paroxysm Compromises of 3 stages:- Cold stage : Patient feels intense cold and shivering Hot stage : Patient develops high fever – 40.0°-40.6°C , severe headache and vomitting Sweating stage : Patient sweats profusely

48. Splenomegaly Enlarged spleen is observed after paroxysms which is often palpable

49. Hepatomegaly

50. Anaemia Anaemia of a microcytic or normocytic hypochromic type develops due to hemolysis of infected and as well as uninfected RBC’s Therefore patient may complain of extreme fatigue,myalgia and weakness

51. Complications of P.Falciparum M alaria Pernicious Malaria: Arises due to heavy parasitization Manifestations are grouped as: Cerebral malaria : Hyperpyrexia , confusion , palsy, abnormal posturing coma and paralysis Algid Malaria: severe abdominal pain , vomitting , diarhhea , low blood pressure , and cold clammy skin Septicaemic Malaria: continuous fever , shock , liver or kidney failure

52. Black water fever: A complication of  malaria in which  RBC’s burst in the bloodstream releasing   hemoglobin directly into the blood vessels  and into the urine, frequently leading to  kidney failure . Occurs in persons who have been previously infected. Clinical manifestations include: Bilious vommiting Intense Jaundice Anuria Passage of dark red or blackish urine

53. LABORATORY DIAGNOSIS OF MALARIA

54. Lab Diagnostic Techniques Light Microscopy Fluorescent Microscopy Quantitative buffy coat test Serological tests Molecular methods Rapid diagnostic tests

55. Light Microscopy Most reliable, economic and preferred diagnostic procedure in malaria. Specimen : Peripheral Blood Two types of peripheral blood smears are prepared:

56. Light Microscopy

57. Light Microscopy All asexual erythrocytic stages (ring forms, trophozoites , schizonts ) as well as gametocytes detected in P. vivax, P. malariae, P. ovale. Only ring forms and gametocytes detected in P. falciparum .

58. 2. Plasmodium vivax Presence of Schuffner’s dots Enlarged RBCs. 1. Plasmodium ovale Presence of Schuffner’s dots Schizonts do not have more than 12 nuclei. Light Microscopy

59. Light Microscopy 3. Plasmodium malariae Presence of Ziemann’s dots . 4. Plasmodium falciparum Presence of Maurer’s dots . Multiple rings in individual RBCs with accole forms.

60. Fluorescent Microscopy Kawamoto technique: Blood smear stained with acridine orange. Stained slide examined under fluorescent microscope. Nuclear DNA – stained green Cytoplasmic RNA – stained red

61. Quantitative buffy coat test QBC tube coated with acridine orange (fluorescent dye) Blood sample collected in QBC tube centrifuged. Buffy coat examined directly under fluorescent microscope. Acridine -orange stained malarial parasites appear brilliant green.

62. Serological tests Indirect immunofluorescence Indirect Hemagglutinin assay(IHA) Enzyme linked immmunosorbent assay (ELISA ) ELISA Indirect immunofluorescence

63. Molecular Methods Polymerase Chain Reaction More sensitive than microscopy. Amplification of 18S rRNA genes. Expensive Requires specialized laboratory set-up .

64. Rapid diagnostic tests

65. Rapid diagnostic tests Kits available detect: Histidine -rich protein (HRP-II) of P. falciparum. Parasite lactate dehydrogenase ( pLDH ) of all four Plasmodium species can also be detected.

66. Some characteristics of infection with four species of human Plasmodia P.v. P.o. P.m. P.f. Pre-erythroctic stage (days) 6-8 9 14-16 5.5-7 Pre-patent period (days) 11-13 10-14 15-16 9-10 Incubation period (days) 15 (12-17) or up to 6-12 months 17 (16-18) or longer 28 (18-40) or longer 12 (9-14) Erythrocytic cycle (hours) 48 (about) 50 72 48

67. Some characteristics of infection with four species of human Plasmodia P.v. P.o. P.m. P.f. Paraitemia per μl Average Maximum 20,000 50,000 9,000 30,000 6,000 20,000 20,000-50,000 2,000,000 Primary attack* Mild-severe Mild Mild Severe in non-immunes Febrile paroxysms (hours) 8-12 8-12 8-10 16-36 or longer

68. Chloroquine Rapidly acting erythrocytic schizontocide Controls most clinical attacks within 1-2 days Acts mainly on trophozoite blood stage; kills gametocytes of P. vivax , P. ovale , and P. malariae (but not P. falciparum ); no action on liver stages  Dose : 600 mg stat, followed by 300 mg after 6 hours and 300 mg for the next 2 days. Adverse effect: Nausea, dysphoria, pruritus in dark-skinned patients, postural hypotension Hypotensive shock ( parenteral ), cardiac arrhythmias, neuropsychiatric reactions,Retinopathy (cumulative dose, >g), skeletal and cardiac myopathy

69. Quinine Obtained from cinchona bark Acts mainly on trophozoite blood stage Kills gametocytes of P. vivax , P. ovale , and P. malariae (but not P. falciparum ) No action on pre-erythrocytic stages Adverse Effect Cinchonism: A large single dose or higher therapeutic dose taken is k/a CINCHONISM. It includes: - Ringing of ear -Nausea & vomiting -headache & mental confusion -Vertigo -difficulty in hearing -visual defect

70. Primaquine It is highly active against gametocytes and hypnozoites . Active against the pre-erythrocytic stage Poor erythrocytic schizontocide Adverse effects Abdominal pain GI upset Leucopenia Hemolysis in G6PD deficient patients.

71. Artemisinins The most important of these analogs are artesunate , artemether , and arteether . act very rapidly against all erythrocytic-stage human malaria parasites increasing role in the treatment of malaria, including multidrug-resistant P falciparum malaria

72. Treatment During Pregnancy IV quinine Chloroquine Artesunate combinations Quinine and clindamycin Amodiaquine

73. Prevention of Malaria

74. Be A ware: risk factor, incubation period, symptom Avoid being B itten by mosquitoes C hemoprophylaxis Immediately seek D iagnosis & treatment: if fever occur 1 week – 3 months after arrival in endemic areas Key tools of prevention

75. The main strategy for malaria control: Attack the adult mosquitoes, or prevent them from biting people. Some risks: Toxicity of DDT Resistance of mosquitoes

76. What are ways to prevent mosquito bites? Use mosquito repellants. Wear long pants and long sleeves. Wear light-colored clothes. Use window screens Use bed nets.

77. 1. Find out about malaria in your community Visit families to ask them about their experiences with malaria. Ask about bed nets. Check for standing water.

78. 2.Teach about malaria Teach about malaria and malaria prevention. Use health stories for malaria teaching. You will enjoy the malaria comic book. Do skits; make posters; tell stories; be creative! Where can you teach about malaria? During home visits In community meetings At the health center and local school

79. 3. Do community cleanup Encourage the community for cleaning programs so that they work together with you on this. Get rid of any sources of standing water (old tires, cans, jars, pools of water). Cover any water containers.

80. 4. Encourage the use of long-lasting nets and insecticides

81. RECENT ADVANCES

82. An effective vaccine is not yet available for malaria although several are under development The highly polymorphic nature of many P. falciparum proteins results in significant challenges to vaccine design Malaria vaccines in development include: Pre- erythrocytic or liver-stage vaccines That aims to protect against the early stage of malaria infection Blood-stage vaccines That aims to reduce the severity of disease Transmission blocking vaccines That are intended to prevent mosquitoes that fed on an infected person from spreading malaria to new hosts

83. Vaccine candidates that target antigens on gametes, zygotes, or ookinetes in the mosquito aims to block the transmission of malaria. These transmission-blocking vaccines induce antibodies in the human blood; when a mosquito takes a blood meal from a protected individual, these antibodies prevent the parasite from completing its development in the mosquito.

84. Vaccines SPf66 RTS,S or Mosquirix PfSPZ

85. SPf66 This vaccine was tested extensively in endemic areas in the 90s, but clinical trials showed it to be ineffective.

86. RTS,S RTS,S or Mosquirix is an experimental recombinant protein-based vaccine for malaria expected to be licensed in 2015. It targets the pre- erythrocytic stage of the parasite’s life cycle. Infection is prevented by inducing high antibody titers that block the parasite from infecting the liver.

87. PfSPZ It is a pre- erythrocytic attenuated vaccine that uses whole sporozoites to induce an immune response Sanaria , a US biotech company, is involved in it.

88. World Malaria Day, April 25 The theme for 2014 and 2015 was: “Invest in the future. Defeat malaria”

89. T hank You