Drug-Resistant Malaria - libdoc.who.int - World Health Organization

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114 / APPENDICES Chloroquine is effective against the asexual blood stages of susceptible strains of Plasmodium falciparum, resulting in a radical cure of this infection. It is generally well tolerated 1.n a therapeutic regimen, occasionally causing nausea, vomiting, dizziness, hypotension, headache, blurring of vision and pruritus. The more serious ocular damage due to drug induced retinopathy occurs only with repeated high doses for months or years. The maximum safe dose has been estimated to be a total of 100 g over 2 1/2 to 6 1/2 years. There are no reports of teratogenic effects in humans when chloroquine has been used as an antimalarial drug and it may therefore be administered to women of childbearing age and during pregnancy. Severe hypotension and cardiovascular collapse have been reported following parenteral administration of chloroquine, especially in infants and young children. The drug is metabolized by dealkylation 10 the liver and excreted by the kidneys with a half-life of 55 hours in healthy normal adults. Dosage reduction may be necessary 1n patients with severe hepatic or renal disease, though there are little data on this po<strong>int</strong> and some authorities have recommended that the standard therapeutic regimen be employed 1n these patients. 1.2 Amodiaquine 7-chloro-4-(3'-diethylaminomethyl-4'-hydroxyanilino) quinoline Trade names: Camoquin, Basoquin, Flavoquine Formulations available: Tablets of 150 mg and 200 mg (base) and a suspension of 150 mg/5 ml Regimen: Adults - 600 mg (base) initially then 400 mg at 24 and 48 hours l Children - 10 mg/kg initially then 5 mg/kg at 24 and 48 hours The efficacy and side effects of amodiaquine are essentially the same as chloroquine. Recononendations and precautions may be regarded as equivalent. The re are in vivo and in vit ro data suggesting that amodiaquine is more active than chloroquine against strains of P.falciparum resistant to the latter drug, but 1 With 150 mg tablets formulat ion, the same regimen as with chloroquine is used.
APPENDICES / 115 not of sufficient magnitude to support recormnendation of its use in known resistant infections, without additional research. 1.3 Quinine 6-methyoxy-~ - Trade names: (5-vinyl-2-quinuclidinyl)-4-quinolinemethanol Quinine, Coco-quinine, Quinimax Formulations available: Quinine sulfate tablets of 130 mg, 200 mg, and 325 mg; suspension 110 mg/5 ml Regimen: Adults - 650 mg every 8 hours for 7-14 days 1 Children - 10 mg/kg every 8 hours for 7-14 days Quinine is active against asexual erythrocytic stages of all forms of human malaria. Quinine is regarded by many experienced clinicians as the most rapidly active drug for the treatment of severe cases of falciparum malaria. A suppressive cure can be achieved with quinine alone but this drug is less efficient than 4-aminoquinolines for that purpose. A common syndrome of characteristic side effects known as cinchonism occurs in many patients taking quinine. Giddiness, lightheadedness, transient hearing loss, tinnitus, tremors, amaurosis and blurred vision may appear during the first 2-3 days of therapy. These do not necessitate discontinuation of treatment and subs ide quickly when the drug is stopped. Other less frequent but more serious side effects of quinine include urticaria, "asthma", fever, pruritus, thrombocytopenia, haemolysis, and oedema of the eyelids, mucous membranes and lungs. These may occur following a sing le dose and require irmnediate discontinuation of the drug. Cardiovascular collapse may follow rapid <strong>int</strong>ravenous infusion of quinine. There is a limited risk of inducing abortion with the use of quinine in pregnancy. Pregnant women are frequently hypersusceptible to acute haemolytic anaemia or thrombocytopenia due to the drug. Less than 5% of an administered dose of quinine is excreted unchanged in the urine. Most of the drug appears in the urine as hydroxylated metabolites in patients with normal hepatic function. Hepatic dysfunction due to liver disease or sustained fever can prolong the half-life of quinine, which is normally less than two hours. Monitoring blood levels is recormnended when the drug is used 1n patients with impaired renal or hepatic function. 1 Experience in some areas indicates that use of quinine beyond 7 days is of limited additional benefit.
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Drug-Resistant Malaria The Report o
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Foreword A meeting on drug-resistan
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CONTENTS Page Drug Pressure and Res
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2 / INTRODUCTION Differences in dru
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II. Opening Address and Messages Ol
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OPENING ADDRESS / 7 phical boundari
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OPENING ADDRESS / 9 to preserve for
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OPENING ADDRESS / 11 is also here a
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Ill. Review of Drug Resistance in P
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REVIEW I 15 Table 1. Sensitivity Te
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REVIEW / 17 Other Studies Validatio
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Distribution of Chloroquine-Resista
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REVIEW I 21 are signs to suggest th
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REVIEW / 23 (h) specialized investi
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REVIEW / 25 TABLE 3~ Comparison of
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REVIEW / 27 Of 22 mefloquine in vit
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REVIEW / 29 operational conditions
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REVIEW / 31 the possible influence
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IV. Monitoring of Drug Response of
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MONITORING / 35 during recent years
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MONITORING / 37 India, Sri Lanka an
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Table 4. Results of Micro In Vitro
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MONITORING / 41 The superiority of
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MONITORING / 43 input of the result
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MONITORING / 45 table time 1ag and
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Table 6. Probability of Detecting t
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MONITORING / 49 prevalence = 10% an
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MONITORING / 51 TDR. At the end of
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54 / RESEARCH RESULTS characteristi
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56 / RESEARCH RESULTS EXO-ERYTHROCY
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VI. Control of Drug-Resistant P. fa
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CONTROL / 61 DRUG USE AIMING AT PRE
Page 71 and 72: Table 7. Specific Actions for the C
Page 73 and 74: CONTROL / 65 Table 8. Drugs or Comb
Page 75 and 76: Table 9. Suggested Use of Antimalar
Page 77 and 78: Table 9. Suggested Use of Antimalar
Page 79 and 80: CONTROL / 71 Radical therapy of mic
Page 81 and 82: CONTROL / 73 Tanzania several years
Page 83 and 84: VII. Field and Laboratory Research
Page 85 and 86: RESEARCH FOR CONTROL / 77 In vivo a
Page 87 and 88: RESEARCH FOR CONTROL / 79 migrants
Page 89 and 90: RESEARCH FOR CONTROL / 81 and Phase
Page 91: RESEARCH FOR CONTROL / 83 (b) Metho
Page 94 and 95: 86 / RECOMMENDATIONS and sulfonamid
Page 96 and 97: 88 / RECOMMENDATIONS (xiii) Simple
Page 99 and 100: IX. Summary The Meeting on Drug-Res
Page 101 and 102: APPENDIX 1 List of Participants, Ob
Page 103 and 104: APPENDICES / 95 Sri Lanka Dr M.K. B
Page 105 and 106: APPENDICES / 97 Papua New Guinea Dr
Page 107 and 108: APPENDICES / 99 TEMPORARY ADVISERS
Page 109 and 110: APPENDICES / 101 Dr L.E. Molineaux
Page 111 and 112: APPENDIX 2 List of Documents A. WOR
Page 113 and 114: APPENDICES / 105 Comparative study
Page 115 and 116: APPENDIX 3.1 I 107 RESPONSE OF Plas
Page 117: APPENDIX 3.2 / 109 RESPONSE OF P. F
Page 120 and 121: 112 / APPENDICES 0.25 0.50 0.75 1.0
Page 124 and 125: 116 / APPENDICES 1.4 Sulfonamide pl
Page 126 and 127: 118 / Various tetracycline analogs
Page 128 and 129: 120 / APPENDICES A loading dose on
Page 130 and 131: 122 / APPENDICES The drug should be
Page 132 and 133: 124 / APPEND ICE S 2. INDICATIONS f
Page 134 and 135: 126 / APPENDICES they are already r
Page 136 and 137: 128 / APPENDICES 5.2 In suppressive
Page 138 and 139: 130 / APPENDICES Outline research p
Page 140 and 141: 132 / APPENDICES Long-term To preve
Page 143 and 144: APPENDIX 8 Considerations Related t
Page 145 and 146: APPENDICES / 137 4. Screening point
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