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

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CONTENTS Page Drug Pressure and Resistance .......... . Drug Combinations and Synergism in Relation to the Prevention of the Development of Drug Resistance Exo-Erythrocytic Development of Malaria Parasites. Chloroquine Retinopathy ..... Clinicl-ll Pharmacological Studies .•....... 54 55 56 56 56 VI. CONTROL OF DRUG-RESISTANT P.FALCIPARUM Control of Transmission and Prevalence Drug Use Aiming at Preventing, Delaying or Reversing the Selection of Resistant P. falciparum •• ......•.••••... 59 59 63 VII. FIELD AND LABORATORY RESEARCH FOR THE CONTROL OF RESISTANT P.FALCIPARUM 75 GENERAL TOPICS . SPECH'IC TOPICS PRIORITY TOPICS 75 76 81 VITI. RECOMMENDATIONS 85 IX National and International Cooperaztion Parasite Genetics .......... . Evaluation and Development of Antimalarial Drugs Training SUMMARY 86 86 87 88 91 APPENDICES 1. List of Participants, Observers and Secretariat . . . . • . . . 93 2. List of Documents . . . . . . . . 103 3. Response of P.falciparum to Chloroquine and Mefloq;:;T;;; . . . • . • • . . 107 l~. Sample Size in Studies on Drug Response of Plasmod ium falc iparum . . . . . . III 5. Antimalarial Drugs and Drug Regimens ( F a 1 c i p a rum Ma 1 a r i a ) • • . . . . . 11 3 6. Future Deployment of Mefloquine and Essentil-ll Measures for Protecting Mefloquine Against Resistance . . . . . . . . . • . . . . 123 7. Outline Research Proposals. • • . . • . 129 8. Considerations Related to the Practical Performance of the Assessment of Drug Sensitivity in Plasmodium falciparum •••••. 135
1. Introduction Antimalarial drugs have ahJays played an important role In malaria contro 1. Quini ne was the first dru1c to be employed ~n this context, followed later by tbe syntlll,t ic drugs such as 4-aminoquinolines, dihydrofolate reductase (DHFR) inhibitors and sulfonamides. The IVorld Health Organization convened several Scientific Group meetings to cons ider di fferent aspects of malaria chemotherapy, the use of antimalarials, the status of research in this field anc! the reslstance of plasmodia to antimalarial drugs. The deliberations of these groups have heen published ~n the IVHO Technical Report Series. In 1955, WHO published a monograph on the Chemotherapy of Malaria, the second edition of which has just been published (WHO Monograph Series No. 27, second edition, Geneva, IVorld Health Organization, 1981). In its 8th, 9th, 12th, 14th, 16th and 17th meetings, the WHO Expert Committee on Malaria referred to antimalarial drugs and stressed the importance of their use for accelerating the elimination of the parasite reservoir, for interrupting malaria transmission and for dealing effectively with residual foci and with imported cases. The Malaria Eradication Programmes init iated In the late 1950s therefore laid emphasis on the strategic use of antimalarials, but did not usually employ them as attack measures. However, it has to be realized that ~n cert ain countries the use of drugs may be a maj or, if not the only method available for depleting the malaria reservoir.
Page 1: Drug-Resistant Malaria The Report o
Page 5: Foreword A meeting on drug-resistan
Page 10 and 11: 2 / INTRODUCTION Differences in dru
Page 13 and 14: II. Opening Address and Messages Ol
Page 15 and 16: OPENING ADDRESS / 7 phical boundari
Page 17 and 18: OPENING ADDRESS / 9 to preserve for
Page 19 and 20: OPENING ADDRESS / 11 is also here a
Page 21 and 22: Ill. Review of Drug Resistance in P
Page 23 and 24: REVIEW I 15 Table 1. Sensitivity Te
Page 25 and 26: REVIEW / 17 Other Studies Validatio
Page 27 and 28: Distribution of Chloroquine-Resista
Page 29 and 30: REVIEW I 21 are signs to suggest th
Page 31 and 32: REVIEW / 23 (h) specialized investi
Page 33 and 34: REVIEW / 25 TABLE 3~ Comparison of
Page 35 and 36: REVIEW / 27 Of 22 mefloquine in vit
Page 37 and 38: REVIEW / 29 operational conditions
Page 39 and 40: REVIEW / 31 the possible influence
Page 41 and 42: IV. Monitoring of Drug Response of
Page 43 and 44: MONITORING / 35 during recent years
Page 45 and 46: MONITORING / 37 India, Sri Lanka an
Page 47 and 48: Table 4. Results of Micro In Vitro
Page 49 and 50: MONITORING / 41 The superiority of
Page 51 and 52: MONITORING / 43 input of the result
Page 53 and 54: MONITORING / 45 table time 1ag and
Page 55 and 56: Table 6. Probability of Detecting t
Page 57 and 58: MONITORING / 49 prevalence = 10% an
Page 59:
MONITORING / 51 TDR. At the end of
Page 62 and 63:
54 / RESEARCH RESULTS characteristi
Page 64 and 65:
56 / RESEARCH RESULTS EXO-ERYTHROCY
Page 67 and 68:
VI. Control of Drug-Resistant P. fa
Page 69 and 70:
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 122 and 123:
114 / APPENDICES Chloroquine is eff
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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