Malaria

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Malaria

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Malaria

  1. 1. MALARIA Dr.T.V.Rao MDDR.T.V.RAO MD 1
  2. 2. HISTORY AND FUTURE RESEARCH• One of the oldest known diseases.• King Tut died of malaria.• Malaria has been infecting humans for over 50,000 years.• References to malaria have been recorded for nearly 6000 years, starting in China.• Used to be common in Europe and North America.• First advances in malaria were made in 1880 by a French army doctor named Charles Laveran.• He looked into infected red blood cells and discovered the parasite was a protist. This was the first time a protist was discovered to cause a disease.• Carlos Finlay discovered that mosquitoes transmitted diseases. DR.T.V.RAO MD 2
  3. 3. MALARIA – HISTORY WHO MADE ITAlphonse Laveran Sir Patrick Manson Sir Ronald Ross Giovanni GrassiDR.T.V.RAO MD 3
  4. 4. It was discovered more than 100 years agoA French army doctor inAlgeria observedparasites inside redblood cells of malariapatients and proposedfor the first time that aprotozoan causeddisease Charles Louis Alphonse LaveranDR.T.V.RAO MD 4
  5. 5. RONALD ROSS DISCOVERS THE ROLE OF MOSQUITOS AND TRANSMISSION• Ronald Ross discovered that mosquitoes transmitted malaria in 1898.• First effective medicine was discovered by Pierre Pelletier and Joseph Caventou. This medicine is called quinine, which comes from the bark of cinchona trees in Peru.• No effective vaccine: only immunity is a result of multiple infections.DR.T.V.RAO MD 5
  6. 6. MALARIA – HOT SPOTS GEOGRAPHIC DISTRIBUTIONDR.T.V.RAO MD 6
  7. 7. PRESENT GEOGRAPHICAL DISTRIBUTION OF MALARIADR.T.V.RAO MD 7
  8. 8. DR.T.V.RAO MD 8
  9. 9. MALARIA in • 40% of the world’s population lives endemic areas • 3-500 million clinical cases per year • 1.5-2.7 million deaths (90% Africa) • increasing problem (re-emerging disease) • resurgence in some areas • drug resistance ( mortality) • causative agent = • P. falciparum Plasmodium species • P. vivax • protozoan parasite • member of Apicomplexa • P. malariae • 4 species infecting humans • P. ovale • transmitted by anopholine mosquitoesDR.T.V.RAO MD 9
  10. 10. WHAT IS MALARIA? • Malaria is a parasite that enters the blood. • This parasite is a protozoan called plasmodium. • 3 to 700 million people get malaria each year, but only kills 1 to 2 million • 40% of the worlds population lives in malaria zones • Malaria zones are: Africa, India, Middle East, Southeast Asia, Central and South America, Eastern Europe, and the South Pacific (slide 13).DR.T.V.RAO MD 10
  11. 11. WHAT DETERMINES THE SPREAD OF MALARIA? Malaria spread depends on: •Rainfall pattern (How does this affect mosquito breeding?) ? •Types of mosquitoes in the area •How close are people to the breeding sites? Some areas constantly have a high rate of malaria. Other areas have “malaria seasons” or occasionalepidemics of malaria. DR.T.V.RAO MD 11
  12. 12. MALARIA BURDEN CLINICAL MANIFESTATIONS Hypoglycemia Anemia Acute Severe illness Respiratory Death febrile distress illness Cerebral malariaInfectedMosquito Anemia Chronic Neurologic/ Impaired Malnutrition effects cognitive growth andInfected development Developmental Human Fetus Low birth weight Infant mortality Pregnancy Acute illness Maternal Impaired DR.T.V.RAO MD Anemia productivity 12
  13. 13. MALARIA PARASITE (PLASMODIUM)• Pathogen of malaria• P.vivax ; P.falciparum ;P.malariae ; P.ovale• P.vivax ; P.falciparum are more common• Plasmodium is a wide distribution in many tropical or subtropical regions of the world DR.T.V.RAO MD 13
  14. 14. MALARIA – VECTORS Anopheles balabacensis A. gambiae A. freeborni A. stephensiDR.T.V.RAO MD 14
  15. 15. CHARACTERISTIC OF LIFE CYCLE• Intermediate host : human• Final host : mosquito• Infective stage : sporozoite• Infective way : mosquito bite skin of human• Parasitic position : liver and red blood cells• Transmitted stage : gametocytes• Schizogonic cycle in red cells : 48 hrs/P.v• Sporozoite : tachysporozite and bradysporozite DR.T.V.RAO MD 15
  16. 16. MOSQUITOES AND MALARIA • The spread of malaria depends on the life cycle of the mosquito. • Adult mosquitoes lay their eggs on water. • The eggs hatch to become larvae and then pupae, before turning into adults. • Adult females mosquitoes only live 2 to 4 weeks. • So you can reduce malaria by attacking any of these four stages of the mosquito.DR.T.V.RAO MD 16
  17. 17. Life Cycle • sporozoites injected during mosquito feeding • invade liver cells • exoerythrocytic schizogony (merozoites) • merozoites invade RBCs • repeated erythrocytic schizogony cycles • gametocytes infective for mosquito • fusion of gametes in gut • sporogony on gut wall in hemocoel • sporozoites invade salivary glandsDR.T.V.RAO MD 17
  18. 18. Invasive Stages Merozoite • erythrocytes Sporozoite • salivary glands • hepatocytes Ookinete • epitheliumDR.T.V.RAO MD 18
  19. 19. DR.T.V.RAO MD 19
  20. 20. SPECIES CHARACTERISTICS PV PO PM PFPeriodicity(hrs.) 48 50 72 48Parasites/Ml 20-50 9-30 6-20 50-2000RBC Age Young Young Old AnyHyponozoite Yes Yes No NoDuration (yrs.) 1.5-5 1.5-5 3->50 1-2 DR.T.V.RAO MD 20
  21. 21. MORPHOLOGY • Malarial parasite trophozoites are generally ring shaped, 1-2 microns in size, although other forms (ameboid and band) may also exist. • The sexual forms of the parasite (gametocytes) are much larger and 7-14 microns in size. • P. falciparum is the largest and is banana shaped, while others are smaller and round.DR.T.V.RAO MD 21
  22. 22. EXO-ERYTHROCYTIC S HYPNOZOITES GAMETOCYTES ERYTHROCYTICDR.T.V.RAO MD 22
  23. 23. DR.T.V.RAO MD 23
  24. 24. Exoerythrocytic Schizogony • hepatocyte invasion • asexual replication • 6-15 days • 1000-10,000 merozoites • no overt pathologyDR.T.V.RAO MD 24
  25. 25. Hyponozoite Forms • some EE forms exhibit delayed replication (ie, dormant) • merozoites produced months after initial infection • only P. vivax and P. ovale relapse = hypnozoite recrudescence = subpatenttDR.T.V.RAO MD 25
  26. 26. IS IT FALCIPARUM? • WHAT DOES THE SMEAR SHOW? • >3% PARASITEMIA • MONOTONOUS SMALL RINGS • NO TROPHOZOITES OR SCHIZONTS • BANANA SHAPED GAMETOCYTES • MULTIPLY INFECTED CELLS • APPLIQUE FORMS • CELLS OF ALL SIZES INFECTEDDR.T.V.RAO MD 26
  27. 27. HOW THE PARASITE APPEARS IN BLOOD SMEARDR.T.V.RAO MD 27
  28. 28. DR.T.V.RAO MD 28
  29. 29. P. FALCIPARUM – BLOOD STAGES Uninfected RBC 4 hr. 12 hr. 2 hr.DR.T.V.RAO MD 29
  30. 30. erythrocytic schizogony • 48 hr in Pf, Pv, Po • 72 hr in Pm gametocytesDR.T.V.RAO MD 30
  31. 31. Gametocytogenesis • alternative to asexual replication • induction factors not known • drug treatment  #s • immune response  #s • ring  gametocyte • Pf : ~10 days • others: ~same as schizogony • sexual dimorphism • microgametocytes • macrogametocytes • no pathology • infective stage for mosquitoDR.T.V.RAO MD 31
  32. 32. GAMETOCYTES Male gametocyte Female gametocyte Note: compact cytoplasm and absence of nuclear division.DR.T.V.RAO MD 32
  33. 33. GAMETOCYTE OF P. FALCIPARUM banana shaped gametocyte ( P. falciparum)DR.T.V.RAO MD 33
  34. 34. Gametogenesis • occurs in mosquito gut • ‘exflagellation’ most obvious • 3X nuclear replication • 8 microgametes formed • exposure to air induces •  temperature (2-3oC) •  pH (8-8.3) • result of  pCO2 • gametoctye activating factor in mosquito • xanthurenic acidDR.T.V.RAO MD 34
  35. 35. Sporogony • occurs in mosquito (9-21 d) • fusion of micro- and macrogametes • zygote  ookinete (~24 hr) • ookinete transverses gut epithelium (trans-invasion)DR.T.V.RAO MD 35
  36. 36. Sporogony • ookinete  oocyst • between epithelium and basal lamina • asexual replication  sporozoites • sporozoites releasedDR.T.V.RAO MD 36
  37. 37. Sporogony • sporozoites migrate through hemocoel • sporozoites invade salivary glandsDR.T.V.RAO MD 37
  38. 38. INCUBATION PERIOD Following the infective bite by the Anopheles mosquito a period of time (the "incubation period") goes by before the first symptoms appear. The incubation period in most cases varies from 7 to 30 days. The shorter periods are observed most frequently with P. falciparum and the longer ones with P. malariae.DR.T.V.RAO MD 38
  39. 39. Clinical Features• characterized by acute febrile attacks (malaria paroxysms) • periodic episodes of fever alternating with symptom-free periods• manifestations and severity depend on species and host status • immunity, general health, nutritional state, genetics• recrudescences and relapses can occur over months or years• can develop severe complications (especially P. falciparum) DR.T.V.RAO MD 39
  40. 40. Malaria Paroxysm • paroxysms associated with synchrony of merozoite release • between paroxysms temper- ature is normal and patient feels well • falciparum may not exhibit classic paroxysms (continuous fever) tertian malaria quartan malariaDR.T.V.RAO MD 40
  41. 41. CLINICAL MANIFESTATIONS1 Anemia2 Splenomegaly3 Cerebral malaria4 Malaria nephropathy5 Congenital malaria usually fatal6 black water fever… DR.T.V.RAO MD 41
  42. 42. WHAT ARE THE SIGNS AND SYMPTOMS OF MALARIA? Symptoms of malaria include fever and flu-like illness, including shaking chills, headache, muscle aches, and tiredness. Nausea, vomiting, and diarrhea may also occur. Malaria may cause anemia and jaundice (yellow coloring of the skin and eyes) because of the loss of red blood cells. Infection with one type of malaria, Plasmodium falciparum, if not promptly treated, may cause kidney failure, seizures, mental confusion, coma, and death.DR.T.V.RAO MD 42
  43. 43. UNCOMPLICATED MALARIA The classical (but rarely observed) malaria attack lasts 6-10 hours. It consists of a cold stage (sensation of cold, shivering) ; a hot stage (fever, headaches, vomiting; seizures in young children) and finally a sweating stage (sweats, return to normal temperature, tiredness)DR.T.V.RAO MD 43
  44. 44. IS IT FALCIPARUM?• WHAT DOES THE SMEAR SHOW? • >3% PARASITEMIA • MONOTONOUS SMALL RINGS • NO TROPHOZOITES OR SCHIZONTS • BANANA SHAPED GAMETOCYTES • MULTIPLY INFECTED CELLS • APPLIQUE FORMS • CELLS OF ALL SIZES INFECTED DR.T.V.RAO MD 44
  45. 45. •RELAPSE----aspecific attack that it is up to months or even years after the primary attacks. ----The bradysporozoites in the liver spend a rest and sleeping times of months or even years , then they start develop in Exoerythrocytic stage and erythrocytic stage. at this time, the patient occurs paroxysm , showing as periodic fever like the primary attacks, it is called relapse. ----Relapse only occurs in DR.T.V.RAO MD P.vivax 45
  46. 46. •MALIGNANT MALARIA Malaria caused by P.falciparum. is more severe thanthat caused by other plasmodia.----The serious complication of P.falciparum. involvescerebral malaria (involving the brain); massivehaemoglobinuria (blackwater fever) in which the urinebecomes dark in color, because of acute hemolysis ofRBC; acute respiratory distress syndrome; severegastrointestinal symptoms; shock and renal failurewhich may cause death. DR.T.V.RAO MD 46
  47. 47. LABORATORY DIAGNOSIS laboratory diagnosis of malaria is confirmed by---- the demonstration of malarial parasites in the blood film under microscopic examination.• Thin film• Thick film DR.T.V.RAO MD 47
  48. 48. ANTIGEN DETECTION METHODS• Various test kits are available to detect antigens derived from malaria parasites. Such immunologic ("immunochromatographic") tests most often use a dipstick or cassette format, and provide results in 2-15 minutes. These "Rapid Diagnostic Tests" (RDTs) offer a useful alternative to microscopy in situations where reliable microscopic diagnosis is not availableDR.T.V.RAO MD 48
  49. 49. SEROLOGY IN MALARIA • Serology detects antibodies against malaria parasites, using either indirect immunofluorescence (IFA) or enzyme-linked immunosorbent assay (ELISA). Serology does not detect current infection but rather measures past exposure.DR.T.V.RAO MD 49
  50. 50. MOLECULAR DIAGNOSIS OF MALARIA • Parasite nucleic acids are detected using polymerase chain reaction (PCR). Although this technique may be slightly more sensitive than smear microscopy, it is of limited utility for the diagnosis of acutely ill patients in the standard healthcare setting. PCR results are often not available quickly enough to be of value in establishing the diagnosis of malaria infection.DR.T.V.RAO MD 50
  51. 51. PCR IS USEFUL IN SPECIES DETECTION• PCR is most useful for confirming the species of malarial parasite after the diagnosis has been established by either smear microscopy or RDT.DR.T.V.RAO MD 51
  52. 52. TREATMENT Faciparum? Yes No Fansidar or Vivax or Ovale Malariae Artemeter/Lumefantrine Chloroquine Check G6PD Chloroquine PrimaquineDR.T.V.RAO MD 52
  53. 53. TREATMENT• HALOFANTRINE• MALARONE • ATOVAQUONE/PROGUANIL• TAFENOQUINE• QUININE based regimens• CHLOROQUINE/PROGUANIL IS AN INFERIOR REGIMEN AND SHOULD NOT BE USEDDR.T.V.RAO MD 53
  54. 54. 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.DR.T.V.RAO MD 54
  55. 55. INSECTICIDE-TREATED NETS (ITNS)• What is happening here?• What needs to happen within six months?• Can you think of any practical challenges? Source: HEPFDC, 2009. DR.T.V.RAO MD 55
  56. 56. ORIGINAL ERADICATION PLANS • Interruption of transmission of main species infecting humans by DDT spraying • Malaria disappears spontaneously in under 3 yearsSource: GabaldonDR.T.V.RAO MD 56
  57. 57. OTHER WAYS TO PREVENT MALARIA Who is at the highest risk of malaria? • Travelers to an area high in malaria • Travelers often take prophylactic (preventive) medicines to prevent malaria. • Pregnant women (especially those with HIV) • Pregnant women are given intermittent preventive treatment. They are given at least 2 doses of a malaria drug during their pregnancy. • Young children • How can you protect young children?DR.T.V.RAO MD 57
  58. 58. MALARIA VACCINE• Scientists are working on a new malaria vaccine.• The vaccine would help protect children from deadly malaria.• The vaccine boosts the immune response against malaria.• However, the vaccine is still being tested.DR.T.V.RAO MD 58
  59. 59. • Programme Created by Dr.T.V.Rao MD for Medical and Health Care Workers in the Developing World • Email • doctortvrao@gmail.comDR.T.V.RAO MD 59

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