MALARIA

1. MALARIA Department of Infectious Diseases Third Affiliated Hospital Sun Yat-sen University Lin Yang

2. 2 ? A parasitic diseases caused by plasmodium species. ? Transmitted by the bite of infected female anopheline mosquitoes. ? Characterized by periodic paroxysm with shaking chills, high fever, heavy sweating. ? Anemia and splenomegaly in cases suffering from several attack of paroxysm.

3. 3 ? P. vivax and P.ovale-caused malaria often relapse. ? P.falcipraum-caused malaria often shows irregular fever, and may occur cerebral malaria.

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5. 5 ? Be epidemic in 92 countries and area ?New cases of malaria a year: 300 to 500 millions ?About two millions cases die a year ?About one million children die of malaria a year ?In China: In 2000: 25,520 cases 42 cases died

6. 6 ¦ Etiology ? Four species of plasmodium cause malaria in human. P. vivax, P. ovale. P. malariae P. falciparum Each species has its own morphologic, biologic, pathogenic, and clinical characteristics.

7. 7 ? P.vivax is the most common. ? P. falciparum--- the most strong pathogenicity causes the cerebral malaria, causes the chief mortality, presents the therapeutic problem of chloroquine resistance.

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12. 12 ? Development of plasmodium in anopheles gametocytes in blood circulation of human female anopheles by bite, sexual reproduction: (gametocytes zygote ookinete oocyst containing sporoblasts infective sporozoite ) humans blood circulation by bite

13. 13 ? life cycle in RBC and periodic paroxysm Clinical periodic paroxysm depend on life cycle of plasmodium in erythrocytes . Different plasmodium, the length of life cycle in RBC is different, so the interval of periodic paroxysm is different. P. vivax, and P. ovale: 48hour P. malariae: 72hour P. falciparum: 36-48hrs, and irregular

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20. 20 ¦ Epidemiology ?Source of infection: patients and carriers ? Route of transmission: bite by infected female anopheles. occasionally, inoculation of blood, e.g. blood transfusion; congenital infection . ? Susceptibility: Universal, all ages and both sexes are susceptible to plasmodium.

21. 21 ? Immunity ? species specific, strain specific, ? last for a short time only. ? No across protective immunity, For example: immunity to P. falciparum does not protect from P.vivax. ?Immunity usually does not prevent from reinfection, but reduce the severity of the diseases or lead to an asymptomatic infection.

22. 22 ? Distribution ? geographic distribution malaria is endemic in the tropics and subtropics, distribution in countries of Africa, Asia and Latin America; ? In China: several provinces: ? P. vivax is the most common in epidemic area, and in China.

23. 23 ? Seasonality Generally, malaria occurs in autumn and summer, but no seasonality,and malaria occur whole year in tropics and subtropics.

24. 24 ¦ Pathogenesis and pathology ? Hepatocellular lesions, hepatomegaly, abnormal liver functions. ?Anemia and splenomegaly Continuous attack results in anemia and splenomegaly.

25. 25 ?Anemia is caused by hemolysis of infected erythrocytes. Severe acute hemolytic anemia may occur in patients infected with very high parasitemia, or patients with G-6-PD deficiency. ? Splenomegaly and hepatomegaly Result from the marked mononuclear hyperplasia after the rupture of erythrocytes.

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27. 27 ? Necrosis of tissue cells, especially in the brain. Agglutination tendency of infected red blood cells and damage of vascular endothelial cells may cause thrombosis, and then result in necrosis of tissue cells.

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29. 29 ? Mechanism of severe malaria Most of severe malaria occur in falciparum malaria. The damage of vascular endothelium and agglutination of infected RBC obstacle in the microcirculation necrosis of tissue cells. P.vivax and P. ovale invade young RBC P. malariae invade old RBC P. falciparum invade all RBC

30. 30 ¦ Clinical manifestations 1. Incubation period 2. Prodromal period 3. Clinical forms Typical form, Mild form, Cerebral malaria, Recrudescence, Relapse.

31. 31 ? Incubation period P. vivax and P. ovale 13~15 days P. malariae 24~30 days P. falciparum 7~12 days

32. 32 ? Prodromal period many patients experience a prodromal period, occur in several days before the onset of paroxysm. nonspecific symptoms, such as malaise, headache, myalgia, fatigue, poor appetite, etc.

33. 33 ? Clinical forms 1> Typical form Periodic attack of paroxysm with shaking chills-- high fever--heavy sweating. ? Shaking chills last for 20 min to 1 hrs, ? high fever: T rise to or over 40?C for 2 to 6 h, with severe headache, myalgia, and skin becomes warm and dry. ? heavy sweating: last for 30 min to 1 h, anemia and moderate splenomegaly in cases with several paroxysms.

34. 34 ? Intermittent period fatigue or being asymptomatic Intermittent period (interval of attack) is determined by the length of asexual erythrocytic cycle: P. vivax and P. ovale , about 48 hrs--- paroxysm attack every other day; P. malariae, about 72 hours paroxysm attack every three days P. falciparum , 36-48 hours; paroxysm attack every 36 to 48 hrs In early stage of paroxysm, intermittent period may irregular.

35. 35 ? Physical examination: Anemia and splenomegaly in patients after several paroxysms. Tender hepatomegaly in less frequently. Other physical findings: Jaundice, urticaria, petechial, rash, etc. may be seen in less frequently.

36. 36 2>.Mild form Often seen in patients living in endemic region of malaria. Clinical manifestations of paroxysm are not so typical. Symptoms are milder, and persistent time is shorter.

37. 37 3>.Cerebral malaria ? The most serious type of malaria. ? generally caused by P. falciparum. ? Clinical manifestations including: High fever, headache, vomiting, delirium, convulsion, coma, positive pathological reflexes. Examination of CSF usually show normal.

38. 38 4>.Recrudescence Appear clinic signs of malaria a short time after primary paroxysm. Induced by non-standard pathogenic therapy or drug resistant plasmodium (merozoites ). Parasites in red blood cells were suppressed by specific drugs, or immunity, but not eradicated, and proliferated again after a short time, and induce clinical manifestations.

39. 39 5>.Relapse appear clinic signs of malaria about three to six months or longer after primary attack. caused by bradysporozoites of P. vivax and P. ovale.

40. 40 Relapse Recrudescence three to six months or longer short time after primary attack after primary attack Caused by bradysporozoites non-eradicated parasite P. vivax and P. ovale. Four species of plasmodium non-standard therapy or drug resistance

41. 41 ¦ Complications ? Hemolytic urinemic syndrome (Black water fever) Often occur in patients with G-6-PD deficiency, may be induced by primaquine treatment or by heavy infection(high parasitemia) with P. falciparum or an atypical immune response during reinfection. Massive RBC rupture and hemolysis. Shows hyperhemoglobinemia: lumbago, malarial hemoglobinuria, anemia, jaundice, acute renal failure.

42. 42 ? Nephropathic syndrome usually occurs in cases of p. malariae infection. Patients with hypertension, edema, massive protein in urine, etc.

43. 43 ¦ Diagnosis ? Epidemiological data ? Clinical manifestations ? Laboratory findings

44. 44 ? Epidemiological data History of living in or traveling to epidemic areas. History of blood transfusion. Neonates was born by malaria mothers. ? Clinical manifestations Periodic paroxysms with shaking chills, high fever, sweating. Anemia and splenomegaly may present. Fever patterns may be irregular in some cases

45. 45 ? Laboratory findings ? WBC, RBC, Hb. Normal white blood cell count, decreased red blood cell count and hemoglobin level. ? Thick and thin blood smear (Giemsa stain) Plasmodium species are found in thick and thin blood smear, or bone marrow smear. --------Definitive diagnosis Thick and thin blood smear are very simple and important

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51. 51 ? Serologic tests : not so important Test antibody against plasmodium ? Test DNA of plasmodium by PCR: high sensitivity ? Therapeutic trial is not advocated because of the side effects of chloroquine and primaquine.

52. 52 ¦ Differential diagnosis ? septicemia ? leptospirosis ? typhoid fever ? bile duct infection ? Japanese encephalitis ? toxic form of shigellosis

53. 53 ? Septicemia •Severe toxemia symptoms, with primary inflammation focus • Positive blood bacterial culture. • Without periodic paroxysm and intermittent period.

54. 54 ? Leptospirosis • The history of contacting contaminated water or wet soil, • enlargement of lymph nodes, persistent high fever, myalgia of the calf muscle. • Positive agglutination-lyse test for antibodies against leptospira species.

55. 55 ? Typhoid fever: Insidious onset, sustained fever, relative bradycardia, rose spots, positive Widal’s reaction and positive blood culture for salmonella typhi. ? Biliary ducts inflammation: sudden onset, with high fever, colic pain in right upper part of abdomen, jaundice. Utrasonography will be very helpful for making the diagnosis.

56. 56 ? Japanese encephalitis and toxic form of shigellosis: should be considered in differential diagnosis of cerebral malaria.

57. 57 ¦ Prognosis Good in ordinary cases. Poor in cerebral malaria and Black Water Fever.

58. 58 ¦ Treatment 1. Symptomatic and supportive treatment 2. Etiologic treatment: A.Control paroxysm treatment B. Prevent relapse C. Prevent transmission

59. 59 ? Symptomatic and supportive treatment High fever, convulsion, cerebral edema, black water fever, etc. ? Keep warm for shaking chill; ? Physical and chemical defervescent methods for high fever, such as ice bag, air condition. Corticosteroid may be given , if necessary. ? diazepam and wintermin for convulsion.

60. 60 ? 20% Mannitol injection fluid intravenous quickly for cerebral edema; Dextran also is useful for cerebral malaria. ? For black water fever, withdraw all anti- malaria drug, and giving dexamethason, small amount of blood transfusion. Giving sodium bicarbonate, and must keep more than 2000ml urine output per day.

61. 61 ?Etiologic treatment ? Treatment principle: 1.Combination anti-paroxysm treatment with preventing from relapse and transmission treatment 2. Ordinary examining G-6-PD before giving primaquine. primaquine only is given in these patients without G-6-PD deficiency

62. 62 ? Anti-paroxysm kill reproducting plasmodia in RBC ? Prevent relapse: kill bradysporozoite primaquine, for 8 days ? Prevent transmission: kill gametocyte primaquine for 3days

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64. 64 ? For P.falciparum and P. malariae-caused malaria Anti-paroxysm drugs and primaguine (for 2-4 days) must be given to control paroxysm and to kill gametocyte for prevent from transmmision although prevent from relapse is not necessary.

65. 65 ? It is necessary to examine G-6-PD before giving primaquine because primaquine may induce acute intravascular hemolysis in patients with G-6-PD deficiency.

66. 66 ? Control paroxysm drugs and treatment 1>.Drugs chloroquine --first choice for sensitive plasmodia artesunate(????) first choice for cerebral malaria artemisinine(???) pyromaridine phosphate(?????) mefloquine(???) quinine sulfate (????) benflumethtolum(???) arteflene(???) naphthoquine phosphate(?????)

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69. 69 3>. chloroquine -resistant plasmodia ?artesunate alone or combination with benflumethtolum. ? mefloquine alone or combination with TMP. ? pyromaridine phosphate + pyrimethamine (????) artemisinine

70. 70 4>. Control paroxysm for cerebral malaria ? artesunate first choice 60mg + 5% sodium bicarbonate solution, First, slowly intravenous drip, then, given orally for 2-3 days after recovering from unconscious. ? chloroquine (sensitive plasmodia) ? pyromaridine phosphate quinine

71. 71 ? Prevent relapse: kill bradysporozoite primaquine 39.6mg(22.5mg base) qd, orally, for 8 days for P. vivax and P. ovale caused malaria to prevent replase. For P.falciparum and P.malariae-malaria, prevent replase is not necessary, but primaquine still must be given for 3 days to kill gametocytes for preventing transmission.

72. 72 ? Prevent transmission primaquine 39.6mg(22.5mg base), qd, orally, for 3 days, for interrupting transmission of P. falciparum malaria and P. malariae malaria by kill gametocytes. Another drug: tafenoquine ??? shows to kill bradysporozoite and gametocyte. 0.3 /day for 7 days.

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74. 74 ¦ Prophylaxis 1.Treatment of patients and carriers 2.Control mosquito vectors 3. Individual protection Avoid mosquito bite chemoprophylaxis with drug chloroquine phosphate 0.5 qw pyrimethamine 0.25 qw doxycycline(????) 0.2 qw

75. 75 Summary ?Malaria is a parasitic diseases caused by plasmodium species, and transmitted by the bite of infected female anopheline mosquitoes. ? Be caused by four species of plasmodium: P. vivax, P. ovale. P. malariae P. falciparum ? Occur major in tropic and subtropic area ? All person are susceptible, and no last immunity ? Life cycle of plasmodium: two hosts, two types of reproduction

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