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Management of Malaria

Hospital for Tropical Diseases, Faculty of Tropical Medicine, Mahidol University. Management of Malaria. ศาสตราจารย์ศรีวิชา ครุฑสูตร ศาสตราจารย์พลรัตน์ วิไลรัตน์ ศาสตราจารย์ศรชัย หลูอารีย์สุวรรณ. WHO Collaborating Centre for Clinical Management of Malaria. Introduction.

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Management of Malaria

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  1. Hospital for Tropical Diseases, Faculty of Tropical Medicine, Mahidol University Management of Malaria ศาสตราจารย์ศรีวิชา ครุฑสูตร ศาสตราจารย์พลรัตน์ วิไลรัตน์ ศาสตราจารย์ศรชัย หลูอารีย์สุวรรณ WHO Collaborating Centre for Clinical Management of Malaria

  2. Introduction

  3. Malaria Mortality Rate, Thailand 1949 - 2005 MR per 100,000 2005: 0.26 Year Department of Permanent Secretariat, MoPH

  4. Case Fatality Rate of Falciparum Malaria, Thailand 1985 - 2005 CFR (%) Year * Preliminary report (OCt04-Sep05) Source: Malaria Cluster, Department of Disease Control, MoPH

  5. Annual Parasite Incidence (API), Thailand 1965 - 2005 API per 1,000 0.49 Fiscal Year * Preliminary report (OCt04-Sep05) Source: Malaria Cluster, Department of Disease Control, MoPH

  6. จำนวนผู้ป่วยมาลาเรียรายเดือน (ผู้ป่วยไทย)(ปีงบประมาณ 2545-2549*) จำนวนผู้ป่วย เดือน * Preliminary report (Oct.05 -Sep.06) Source: Malaria Cluster, Department of Disease Control, MoPH

  7. Diagnosis

  8. Etiology • Infection of red blood cells • Genus Plasmodium • Inoculated into the human hosts: • Anopheline mosquito

  9. Etiology • Phylum: Apicomplexa (Sporozoa) • Class: Haemosporidea (Sporozea) • Order: Haemosporidia • Genus: Plasmodium

  10. Etiology • Human malaria: • P. falciparum • P. vivax • P. malariae • P. ovale • Animal malaria: • P. knowlesi

  11. Clinical Manifestations • Pre-patent period: • Time taken from infection to symptoms • P. falciparum 6-12 days • P. vivax 10-17 days • P. ovale 14 days • P. malariae 28-30 days

  12. Clinical Manifestations • First symptoms: • Non-specific • Systemic viral illness • Headache, lassitude, fatigue, abdominal discomfort and muscle and joint aches • Followed by fever, chills, perspiration, anorexia, vomiting and worsening malaise

  13. Diagnosis • Effective disease management: • Prompt and accurate diagnosis • Diagnosis: • Clinical diagnosis • Parasitological diagnosis

  14. Clinical Diagnosis • Fever or history of fever • Low risk of malaria: • Degree of exposure to malaria • History of fever in the previous 3 days • No features of other severe diseases • High risk of malaria: • History of fever in the previous 24 hours and/or • Presence of anemia (most reliable in young children)

  15. Overdiagnosed on the basis of symptoms alone

  16. Parasitological Diagnosis • Advantages: • Improved patient care • Parasite negative: Another diagnosis must be sought • Prevention of unnecessary exposure to antimalarial • Improved health information • Confirmed treatment failures

  17. Parasitological Diagnosis • Light microscopy: • Low cost • High sensitivity and specificity • Rapid diagnostic tests (RDT): • More expensive • Sensitivity and specificity are variable (temperatures & humidity)

  18. Rapid Diagnostic Test

  19. Basis of Antigen or Enzymatic Activities • Histidine Rich Protein-2 (HRP-2): • Plasmodium antigen • Plasmodium associated lactate dehydrogenase (pLDH): • Enzymatic activity • Immunoassay

  20. The OptiMAL Assay • Detection of an intracellular metabolic enzyme: pLDH • Differentiated between malarial species (pLDH isoforms)

  21. Immunochromatographic Test(ICT)

  22. Paracheck Dipstick Test

  23. Paracheck Dipstick Test • P. falciparumONLY • HRP-2 antigen of P. falciparum • Effective when parasites are over 100/µl

  24. Microscopic Examination

  25. Microscopic Examination • Thin and thick blood smear • Permanent staining • Thick smear: Screening • Thin smear: Species identification • Sample: Finger tip, earlobe, venipuncture with EDTA • Clean, unscratched, grease-free slide

  26. Staining Methods • Giemsa: • Provides significant morphological detail • Wright’s stain: • Combines a fixative and stain in one solution • Field’s stain: • Fast and easy to perform

  27. P. falciparum • No enlarged infected RBC • Rings: • Fine and delicate • Several in one cell • May have two chromatin dots • Presence of marginal or applique forms • Unusual to see developing forms in peripheral blood • Gametocytes: • Crescent shape • Not usually appear for the first four weeks • Maurer’s dots

  28. P. vivax • Enlarged infected RBC • Schuffner’s dots • Mature ring forms: • Large and coarse-ameboid form • Developing forms

  29. P. malariae • No enlarged infected RBC • Ring form: Squarish appearance • Band forms • Mature schizonts: Typical daisy head • Chromatin dots: inner surface of the ring

  30. P. ovale • Enlarged infected RBC • Comet forms • Rings: Large and coarse • Schuffner’s dots • Mature schizonts: • Similar to P. malariae but larger and more coarse

  31. Management of Uncomplicated Malaria

  32. Treatment of P. falciparum Malaria

  33. Atovaquone-Proguanil • Advantages: • Good synergistic effect and more efficacious against P. falciparum including strains resistant to CQ and MQ • Recrudescence is minimized • Limitations: • Hypersensitivity • Presence of renal insufficiency • High cost and less available • Suggested: • Not recommended in children (<11 kg), pregnant and breast feeding women

  34. Quinine plusTetracycline or Doxycycline • Advantages: • High cure rate in areas with decreasing susceptibility of P. falciparum to quinine • Doxycycline has long half-life • Limitations: • Difficult to recommend as first-line treatment • Suggested: • Not recommended for pregnant and breast feeding women, children <8 years of age • Recommended for second-line treatment

  35. Artesunate plus Mefloquine • Advantages: • Reduced adverse reactions of high MQ dose • Limitations: • Multiple dose • Severe adverse reaction • Difficult to monitor adverse reactions • Suggested: • Not viable option as a first-line treatment in intense transmission areas

  36. Artemether-Lumefantrine • Advantages: • Effective and tolerated • No adverse reaction • Increased compliance • Limitations: • Multiple dose • Not recommended for pregnant and breast feeding women • Suggested: • The most viable combination option for areas with intense malaria transmission

  37. Thai National Drug Policy Uncomplicated Falciparum Malaria

  38. Thai National Policy 2007 • First line drugs: • Artesunate (50) 4 tablets PO OD x 3 days • Mefloquine (250) • 3 tablets on Day 0 • 2 tablets on Day 1 • Primaquine (15) 2 tablets on Day 2 • Second line drugs:

  39. Additional Aspects of Clinical Management • Can the patient take oral medication? • Does the patient have very high parasitemia? • Use of antipyretics • Use of antiemetics • Management of seizures

  40. Management of Treatment Failures • Failure within 14 days: • Very unusual in ACT (1-7% in 7 trials, none in 39 trials) • May result from: • Drug resistance • Poor adherence • Unusual PK properties in that individual • Treated with second-line antimalarial • Failure after 14 days: • Retreated with first-line ACT

  41. Definition • First-line treatment: • Treatment routinely recommended for a case of uncomplicated malaria • Second and third-line treatment: • Treatment recommended for treating either a case uncomplicated malaria which: • Has not been cured by the first-line treatment • The first-line drug is contraindicated • Therapeutically superior to first-line drug • Can only be available at higher levels of health care

  42. Recommended Second-Line Antimalarial Treatment • Alternative ACT known to be effective in the region • Artesunate + Tetracycline or Doxycycline or Clindamycin • Quinine + Tetracycline or Doxycycline or Clindamycin

  43. Recommended Second-Line Antimalarial Treatment • Artesunate: 2 mg/kg bw once a day • Tetracycline: 4 mg/kg bw qid • Doxycycline: 3.5 mg/kg bw od • Clindamycin: 10 mg/kg bw bid • Quinine: 10 mg salt/kg bw tid

  44. Treatment of P. vivax, P. malariaeand P. ovale

  45. Thai National Drug Policy Vivax and Ovale Malaria

  46. Vivax & Ovale Malaria • Chloroquine: • Day 0: 2 tab tid • Day 1-2: 2 tab OD • Primaquine: • 15 mg OD for 14 days • Relapse: 20 mg OD for 14 days • G6PD deficient: 45 mg wkly for 8 wks • Pregnancy: None

  47. Treatment of Malaria(P. ovale, P. malariae) • P. ovale • P. malariae

  48. Mixed Malaria Infections

  49. Chloroquine

  50. Chloroquine • Standard antimalarial drug for the past 50 years • Interferes with parasite haem detoxification • Other indications: • Amebic liver abscess • Rheumatoid arthritis • Systemic or discoid lupus erythemathosus • Toxicity: • Prolonged periods for rheumatology patients

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