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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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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
Malaria Mortality Rate, Thailand 1949 - 2005 MR per 100,000 2005: 0.26 Year Department of Permanent Secretariat, MoPH
Case Fatality Rate of Falciparum Malaria, Thailand 1985 - 2005 CFR (%) Year * Preliminary report (OCt04-Sep05) Source: Malaria Cluster, Department of Disease Control, MoPH
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
จำนวนผู้ป่วยมาลาเรียรายเดือน (ผู้ป่วยไทย)(ปีงบประมาณ 2545-2549*) จำนวนผู้ป่วย เดือน * Preliminary report (Oct.05 -Sep.06) Source: Malaria Cluster, Department of Disease Control, MoPH
Etiology • Infection of red blood cells • Genus Plasmodium • Inoculated into the human hosts: • Anopheline mosquito
Etiology • Phylum: Apicomplexa (Sporozoa) • Class: Haemosporidea (Sporozea) • Order: Haemosporidia • Genus: Plasmodium
Etiology • Human malaria: • P. falciparum • P. vivax • P. malariae • P. ovale • Animal malaria: • P. knowlesi
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
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
Diagnosis • Effective disease management: • Prompt and accurate diagnosis • Diagnosis: • Clinical diagnosis • Parasitological diagnosis
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)
Overdiagnosed on the basis of symptoms alone
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
Parasitological Diagnosis • Light microscopy: • Low cost • High sensitivity and specificity • Rapid diagnostic tests (RDT): • More expensive • Sensitivity and specificity are variable (temperatures & humidity)
Basis of Antigen or Enzymatic Activities • Histidine Rich Protein-2 (HRP-2): • Plasmodium antigen • Plasmodium associated lactate dehydrogenase (pLDH): • Enzymatic activity • Immunoassay
The OptiMAL Assay • Detection of an intracellular metabolic enzyme: pLDH • Differentiated between malarial species (pLDH isoforms)
Paracheck Dipstick Test • P. falciparumONLY • HRP-2 antigen of P. falciparum • Effective when parasites are over 100/µl
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
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
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
P. vivax • Enlarged infected RBC • Schuffner’s dots • Mature ring forms: • Large and coarse-ameboid form • Developing forms
P. malariae • No enlarged infected RBC • Ring form: Squarish appearance • Band forms • Mature schizonts: Typical daisy head • Chromatin dots: inner surface of the ring
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
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
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
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
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
Thai National Drug Policy Uncomplicated Falciparum Malaria
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:
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
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
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
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
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
Thai National Drug Policy Vivax and Ovale Malaria
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
Treatment of Malaria(P. ovale, P. malariae) • P. ovale • P. malariae
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