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in-vitro and molecular studies on the resistance of p - Covenant ...

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2.5.5Serology………………………………………………………………….19<br />

2.6 Antimalarial Drugs…………………………………………………………….19<br />

2.6.1 Qu<str<strong>on</strong>g>in</str<strong>on</strong>g><str<strong>on</strong>g>in</str<strong>on</strong>g>e <str<strong>on</strong>g>and</str<strong>on</strong>g> related compounds……………………………………….19<br />

2.6.2 Antifolate drugs………………………………………………………..23<br />

2.6.3 Antibiotics……………………………………………………………..25<br />

2.6.4 Artemis<str<strong>on</strong>g>in</str<strong>on</strong>g><str<strong>on</strong>g>in</str<strong>on</strong>g> compounds……………………………………………….26<br />

2.7 Comb<str<strong>on</strong>g>in</str<strong>on</strong>g>ati<strong>on</strong> <strong>the</strong>rapy with antimalarials………………………………………28<br />

2.7.1 N<strong>on</strong>-Artemis<str<strong>on</strong>g>in</str<strong>on</strong>g><str<strong>on</strong>g>in</str<strong>on</strong>g> based comb<str<strong>on</strong>g>in</str<strong>on</strong>g>ati<strong>on</strong>s…………………………………29<br />

2.7.2 Artemis<str<strong>on</strong>g>in</str<strong>on</strong>g><str<strong>on</strong>g>in</str<strong>on</strong>g>-based comb<str<strong>on</strong>g>in</str<strong>on</strong>g>ati<strong>on</strong>s………………………………………29<br />

2.7.3 Traditi<strong>on</strong>al Antimalarial Herbs………………………………………...31<br />

2.8 Antimalarial Drug Resistance …………………………………………………33<br />

2.8.1 Def<str<strong>on</strong>g>in</str<strong>on</strong>g>iti<strong>on</strong> <strong>of</strong> antimalarial drug <strong>resistance</strong>……………………………..34<br />

2.8.2 Malaria treatment failure………………………………………………34<br />

2.8.3 Mechanisms <strong>of</strong> antimalarial <strong>resistance</strong>………………………………..35<br />

2.8.3.1 Chloroqu<str<strong>on</strong>g>in</str<strong>on</strong>g>e <strong>resistance</strong>………………………………………………...35<br />

2.8.3.2 Antifolate comb<str<strong>on</strong>g>in</str<strong>on</strong>g>ati<strong>on</strong> drugs………………………………………….36<br />

2.9 Spread <strong>of</strong> <strong>resistance</strong>…………………………………………………………....36<br />

2.9.1 Biological <str<strong>on</strong>g>in</str<strong>on</strong>g>fluences <strong>on</strong> <strong>resistance</strong>…………………………………....37<br />

2.9.2 Programmatic <str<strong>on</strong>g>in</str<strong>on</strong>g>fluences <strong>on</strong> <strong>resistance</strong>………………………………..40<br />

2.10 Detecti<strong>on</strong> <strong>of</strong> <strong>resistance</strong>………………………………………………………...42<br />

2.10.1 In vivo tests…………………………………………………………....42<br />

2.10.2 In <str<strong>on</strong>g>vitro</str<strong>on</strong>g> tests…………………………………………………………...43<br />

2.10.3 Animal model <str<strong>on</strong>g>studies</str<strong>on</strong>g>………………………………………………...45<br />

2.10.4 Molecular techniques…………………………………………………45<br />

2.10.5 Case reports <str<strong>on</strong>g>and</str<strong>on</strong>g> passive detecti<strong>on</strong> <strong>of</strong> treatment failure………………46<br />

2.11 The future: preventi<strong>on</strong> <strong>of</strong> drug <strong>resistance</strong>…………………………………….46<br />

CHAPTER THREE – MATERIALS AND METHODS<br />

3.1 Study Area…………………………………………………………………..49<br />

3.2 Study Patients………………………………………………………………..49<br />

3.3 Sampl<str<strong>on</strong>g>in</str<strong>on</strong>g>g Procedure………………………………………………………….49<br />

3.4 Ethical C<strong>on</strong>siderati<strong>on</strong>………………………………………………………...51<br />

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