Malaria

malaria in children

1. MALARIA DR INAYAT ULLAH PGY-1 PEDIATRICS . Shifa International Hospital islamabad . MALARIA 11/17/2014 1

2. INTRODUCTION Name is derived from Italian Mal’ aria or bad air Malaria continues to be most important cause of fever and morbidity in the Tropical world Malaria has been eradicated from Europe, Most of North America, USA South America Korea and Japan, 11/17/2014 2

3. Malaria a vector borne Disease Malaria is a vector-borne infectious disease caused by protozoan parasites. It is widespread in tropical and subtropical regions, including parts of the Americas, Asia, and Africa. Transmission: Via female Anopheles mosquito. 11/17/2014 3

4. DEFINITION Malaria is an acute and chronic illness characterized by paroxysms of fever, chills, sweats, fatigue, anemia, and splenomegaly . It has played a major role in human history, having caused more harm to people than any other infectious disease. Malaria is of overwhelming importance in the developing world today, with an estimated 300–500 million cases and >1 million deaths each year 11/17/2014 4

5. Malaria Kills more people than AIDS Malaria kills in one year what AIDS kills in 15 years. For every death due to HIV/AIDS there are about 50 deaths due to malaria. To add to the problem is the increasing drug resistance to the established drug. 11/17/2014 5

6. History – Events on Malaria 1880 - Charles Louis Alphose Lavern discovered malarial parasite in wet mount 1883 - Methylene blue stain - Marchafava 1891 - Polychrome stain- Romanowsky 1898 - Roland Ross - Life cycle of parasite transmission, wins Nobel Prize in 1902 1948 - Site of Exoerythrocytic development in Liver by Shortt and Garnham 11/17/2014 6

7. Major Developments in 20 th Century 1955 - WHO starts world wide malaria eradication programme using DDT 1970 – Mosquitos develop resistance to DDT Programme fails 1976 – Trager and Jensen in vitro cultivation of parasite 11/17/2014 7

8. Parasites Cause of Malaria Malaria is caused by an infection by one of four single celled Plasmodia species, they are: falciparum , vivax , malariae , and ovale . The most dangerous of the four is.P.falciparum 11/17/2014 8

9. Newer species A fifth species, Plasmodium knowlesi , causes malaria in macaques but can also infect humans. Discovered in 2004. 11/17/2014 9

10. Falciparum most Dangerous Falciparum accounts for 90% of deaths due to malaria and vivax is the most widely spread species because it exists in both temperate and tropical climates (Encarta). The malaria life cycle is a complex system with both sexual and asexual aspects . 11/17/2014 10

11. Route of transmission Vector transmission:- bite by infective female anopheles mosquitoes. Direct transmission blood transfusion, the parasite can live for 14 days in blood bottles under - 4*C. The use of contaminated needles . C ongenital Transmission Mother to newborn(via the placenta) 11/17/2014 11

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14. Events in Humans start with Bite of Mosquito Man – Intermediate host. Mosquito – Definitive host – Sporozoites are infective forms Present in the salivary gland of female anopheles mosquito After bite of infected mosquito sporozoites are introduced into blood circulation. 11/17/2014 14

15. Pre erythrocytic cycle Sprozoites undergo developemtnal phase in the liver cell Sprozoites are elongated and spindle shaped become rounded inside the liver parenchyma Multiple nuclear divisions develop to Schozonts A Schizont contains 20,000 – 50,000 merozoites . 11/17/2014 15

16. Exo-erythrocytic (tissue) phase P. malariae or P. falciparum sporozoites do not form hypnotizes , develop directly into pre- erythrocytic schizonts in the liver Pre- erythrocytic schizogeny takes 6-16 days post infection Schizonts rupture, releasing merozoites which invade red blood cells (RBC) in liver 11/17/2014 16

17. Affinity of Parasite to Erythrocytes P.vivax P.malariae Infectes only young or P.ovale Old Erythocytes maximal parasitemia is 2 percent P.falciparum Infects all age groups Also adhere to the endothelial lining of Blood vessesl Causes the obstruction, Thrombosis and Local Ischemias maximum parasitemia is upto 60 percent. 11/17/2014 17

18. Erythrocytic schizogny Liberated Merozoites penetrate RBC Three stages occur 1 Trophozoites 2 Schizont 3 Merozoite 11/17/2014 18

19. Erythrocytic cycle Ruptured red cells release Merozoites which attack new red cells Continue with Schizogony Repeated cycles will continue In P.falciparum - infected erythrocytes with Schizonts aggregate in the capillaries of brain and other internal organs Only ring forms are seen in the blood smears 11/17/2014 19

20. Schizont The tissue schizont of P.falciparuum , P.malariae ,and P.knowlesi rupture once and donot persist in the liver. While in case of P. ovale and P.vivax tissue schizonts are of 2 types primary type rupture in 6-9 days,and the secondary type remain dormant in the liver cells for weeks,months ,or as long as 5 years and causing relapse of infection. 11/17/2014 20

21. Mosquito cycle A definitive Host – Mosquito 11/17/2014 21

22. Life cycle of malaria parasite in Mosquito Sexual phase Some merozoites differentiate into male and female gametocytes, the forms of Plasmodia infective to mosquitoes. These are taken up by a mosquito during another blood meal. These fuse to form an ookinette in the gut lumen of the mosquito. The ookinette invades the stomach wall to form the oocyst . This in turn develops and releases sporozoites which migrate to the salivary gland of the mosquito. This mosquito then goes on to infect another human host. 11/17/2014 22

23. Clinical Features of Malaria 11/17/2014 23

24. INCUBATION PERIOD AND PRODROMAL SYMPTOMS. Incubation period: P. falciparum , 9-14 days; P. vivax , 12-17 days; P. ovale , 16-18 days, and P. malariae , 18-40 days. The incubation period can be prolonged in patients with partial immunity or incomplete chemoprophylaxis and as long as 6-12 mo for P. vivax . Prodromal symptoms include headache, fatigue, anorexia, myalgia, slight fever, and pain in the chest, abdomen, or joints. 11/17/2014 24

25. How Malaria present Clinically Stage 1 Chills for 15 min to 1 hour Caused due to rupture from the host red cells escape into Blood Present with nausea, vomiting,headache Stage 2 Fever may reach upto 40 c may last for several hours starts invading newer red cells. 11/17/2014 25

26. Clinical Malaria Stage 3 Patient starts sweating, concludes the episode Cycles are frequently Asynchronous Paroxysms occur every 48 – 72 hours In P.malariae pyrexia may lost for 8 hours or more and temperature my exceed 41 c . 11/17/2014 26

27. Periodicity can be clue in Diagnosis and species relation Tertian Malaria: 48h between fevers (P. vivax and ovale ) Quartan Malaria: 72h between fevers (P. malariae ) Tropical Malaria: 48h irregular high fever (P. falciparum ) 11/17/2014 27

28. Congenital malaria is an important cause of abortions , miscarriages , stillbirths, premature births , intrauterine growth retardation, and neonatal deaths Congenital malaria usually occurs in a nonimmune mother with P. vivax or P. malariae . CONGENITAL MALARIA CONGENITAL MALARIA 11/17/2014 28

29. The first sign or symptom most commonly occurs between 10-30 days of age . Signs and symptoms include fever, restlessness, drowsiness, pallor, jaundice, poor feeding, vomiting, diarrhea, cyanosis, and hepatosplenomegaly . Malaria is often severe during pregnancy and may have an adverse effect on the fetus or neonate owing to maternal illness or placental infection even in the absence of transmission from mother to child. CONGENITAL MALARIA (CONT) CONGENITAL MALARIA 11/17/2014 29

30. Malaria the disease 11/17/2014 30

31. Pernicious Malaria Carries a High Mortality On few occasions life threatening complications can occur. Occurs in infections with P.falciparum Associated with Heavy parasitemia Grouped into three types 1. Cerebral Malaria 2 Algid malaria 3 Black water fever 11/17/2014 31

32. Cerebral Malaria Malignant malaria can affect the brain and the rest of the central nervous system. It is characterized by changes in the level of consciousness, convulsions and paralysis. 11/17/2014 32

33. Cerebral Malaria Present with Hyperpyrexia Can lead to Coma Paralysis and other complications. Brain appears congested 11/17/2014 33

34. Complication of P.malariae Can produce Nephrotic syndrome in rare instances Affects mainly children of years age Nephrotic syndrome of this type is usually steroid resistant. 11/17/2014 34

35. Black water Fever It is a manifestation of infection with P.falciparum occuring in persons who have been previously infected and have had been inadequate dose of quinine It is characterized by intravascular hemolysis fever, and Haemoglobunuria Cardiovascular collapse and shock Abnormalities in blood coagulation and thrombocytopenia (decrease in blood platelets) 11/17/2014 35

36. DIAGNOSIS 11/17/2014 36

37. A good history taking Ask the patient number of questions concerning: •Current symptoms such as fever. •Current medications. •Recent travel history to endemic area 11/17/2014 37

38. Physical examination Identify signs consistent with malaria: fever, pallor, jaundice, splenomegaly . Exclude other possible causes of fever (e.g. signs of viral and bacterial infections) Examine rest of the systems to rule out any potential infection causing fever. 11/17/2014 38

39. Microscopy Malaria parasites can be identified by examining under the microscope a drop of the patient's blood, spread out as a "blood smear" on a microscope slide. Prior to examination, the specimen is stained (most often with the Giemsa stain) to give to the parasites a distinctive appearance. This technique remains the gold standard for laboratory confirmation of malaria 11/17/2014 39

40. Thick blood film - Used for detecting malaria: a larger volume of blood is examined allowing detection of even low levels of parasitaemia . Also used for determining parasite density and monitoring the response to treatment. 11/17/2014 40

41. Thin blood film Gives more information about the parasite morphology and, therefore, is used to identify the particular infecting species of Plasmodium. 11/17/2014 41

42. Antigen Detection Methods are Rapid and Precise Antigen Detection 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 available. Malaria RDTs are currently used in some clinical settings 11/17/2014 42

43. Other methods of diagnosis of malaria that are not routinely used in clinical practice . PCR based techniques :- Detects DNA or R NA sequences specific to Plasmodium. Fluorescent techniques :- Relatively low specificity and sensitivity. Cannot identify the parasite species. Serologic tests :-Based on immunofluorescence detection of antibodies against Plasmodium species. Useful for epidemiologic and not diagnostic purposes. 11/17/2014 43

44. DIFFERENTIAL DIAGNOSIS influenza Hepatitis, Sepsis, Pneumonia, Meningitis, encephalitis, Endocarditis , Gastroenteritis, Pyelonephritis , Babesiosis , Brucellosis, Leptospirosis , Tuberculosis, Relapsing fever Typhoid fever, Yellow fever, Amebic liver abscess, Hodgkin disease, and collagen vascular disease. 11/17/2014 44

45. Management of malaria The management of malaria is based on the clinical presentation. In severe malaria, anti malarial therapy must be given Intravenously or Intramuscularly, oral treatment should be substituted as early as possible Doses must be calculated in on a mg/kg of body weight. It is important to weigh the patient, and administer the dose appropriate for weight. 11/17/2014 45

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47. All Plasmodium Species Except Chloroquine -Resistant Plasmodium falciparum Oral Drug of Choice Chloroquine phosphate 10 mg base/kg (maximum: 600 mg base) then 5 mg base/kg (maximum: 300 mg base), 6 hr later, and 5 mg base/kg/24 hr (maximum: 300 mg base) at 24 and 48 hr 11/17/2014 47

48. All Plasmodium Species Except Chloroquine -Resistant Plasmodium falciparum Parenteral Drug of Choice Quinidine gluconate 10 mg/kg loading dose (maximum: 600 mg) over 1-2 hr, then 0.02 mg/kg/min continuous infusion until oral therapy can be started Or Quinine dihydrochloride (not available in the USA)20 mg/kg loading dose over 4 hr, then 10 mg/kg over 2-4 hr q8h (maximum: 1,800 mg/24 hr) until oral therapy can be started 11/17/2014 48

49. P. falciparum Acquired in Areas of Known Chloroquine Resistance Oral Regimen of Choice Quinine sulfate 30 mg/kg/24 hr divided in three doses for 3-7 days (maximum: 650 mg/dose) plus Tetracycline 20 mg/kg/24 hr divided in four doses for 7 days (maximum: 250 mg/dose) or plus Pyrimethamine-sulfadoxine ( Fansidar ) < 1 yr, single dose of 1/4 tablet 1-3 yr, single dose of 1/2 tablet 4-8 yr, single dose of 1 tablet 9-14 yr, single dose of 2 tablets >14 yr, single dose of 3 tablets or Mefloquine hydrochloride 15 mg PO followed by 10 mg/kg PO 8-12 hours later (maximum: 1,250 mg) for 1 day 11/17/2014 49

50. P. falciparum Acquired in Areas of Known Chloroquine Resistance Parenteral Quinidine gluconate Same as for chloroquine-sensitive P. Falciparum or Quinine dihydrochloride Same as for chloroquine-sensitive P. falciparum 11/17/2014 50

51. Prevention of Relapses Plasmodium vivax and Plasmodium ovale Only Primaquine phosphate 0.3 mg base/kg/24 hr for 14 days (maximum: 15 mg base [26.3 mg salt]) 11/17/2014 51

52. ARTEMISININS   Artemisinin derivatives clear parasitemia more rapidly than  quinine  . They are active against a broader life-cycle range of blood stage parasites than quinine and they are active against gametocytes . Artemisinin derivatives include  artesunate   , artemether and artemotil . Artesunate is the preferred artemisinin ; clinical experience with artemether and artemotil drugs is limited and they should not be used for treatment of severe disease. 11/17/2014 52

53. Artesunate i /v The standard dosing regimen for intravenous artesunate consists of five doses: 2.4 mg/kg as the first dose, followed by 2.4 mg/kg at 12 and 24 hours, followed by 2.4 mg/kg once daily Emergence of artemisinin resistance is an important concern therefore combination is prefferred . 11/17/2014 53

54. Artemether 20 LAMOFINTRINE 120 P/O 11/17/2014 54

55. COMPLICATIONS TREATMENT Supportive therapy PRBC transfusion(s) to maintain the hematocrit more than 20%, Exchange transfusion in life-threatening P. falciparum malaria with parasitemia more than 5%, Supplemental O2 and ventilatory support for pulmonary edema or cerebral malaria, Intravenous rehydration for severe malaria, Intravenous glucose for hypoglycemia, Anticonvulsants for cerebral malaria with seizures, Dialysis for renal failure. 11/17/2014 55

56. Chemoprophylaxis Chloroquine and hydroxychloroquine Primaquine 1-2 weeks before travel, weekly while in country, and for 4 weeks afterwards Only used for prophylaxis in areas with p. vivax , and for terminal prophylaxis 11/17/2014 56

57. Chemoprophylaxis Atovaquone-Proguanil Doxycycline Mefloquine 1-2 days before, daily while in country and 7 days after 1-2 days before, daily in country and 4 weeks afterwards 2 weeks before, weekly in country and weekly for 4 weeks afterwards 11/17/2014 57

58. Prevention of Malaria 11/17/2014 58

59. Personal protection Preventing the mosquitoes from entering the house – Close door / windows, especially toilets. Well-constructed houses with window screens Preventing the mosquitoes from hiding – Avoid dark corners/ hanging clothes in rooms Mosquito Control – Avoid stagnant water, insecticide spraying etc. 11/17/2014 59

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61. Protection from mosquito bites – Protective clothing, Mosquito repellants (containing DEET), Insect vaporizers (coils containing pyrethroids ), Insecticide treated bed nets (most effective), Airconditioning 11/17/2014 61

62. Anti-larval measure Using the anti larval measures such as oiling the collection of standing water or dusting them with paris green effectively controlled malaria Some moderm larvicides such as temephos which confer long effect with low toxicity are more widely used 11/17/2014 62

63. Vector control strategy Residual spray: Spraying indoor surface of house with DDT/ malathion . 11/17/2014 63

64. MALARIA VACCINE Are expected to become available to WHO in 2014-2015. Evaluated as an addition to, not a replacement for, existing preventive, diagnostic and treatment measures. Finally, extensive efforts have been made to develop a malaria vaccine but results to date have been disappointing. 11/17/2014 64

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