Modeling response and delayance to parasite clearance time to artemisinin combination therapies (ACT):
Gespeichert in:
| 1. Verfasser: | |
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| Format: | Abschlussarbeit Buch |
| Sprache: | English |
| Veröffentlicht: |
2013
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| Schlagworte: | |
| Online-Zugang: | Volltext https://nbn-resolving.org/urn:nbn:de:bvb:19-168213 Inhaltsverzeichnis |
| Beschreibung: | XIII, 128 S. Ill., graph. Darst. |
Internformat
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| 245 | 1 | 0 | |a Modeling response and delayance to parasite clearance time to artemisinin combination therapies (ACT) |c von Akindeh Mbuh Nji |
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Datensatz im Suchindex
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| adam_text | BESDHR. F. D. AUA
4(0.0$. 2A^
MODELING RESPONSE AND
DELAYANCE TO PARASITE CLEARANCE TIME
TO ARTEMISININ COMBINATION
THERAPIES(ACT)
AKINDEH
MBUH NJI
HTTP://D-NB.INFO/1051404851
TABLE OF CONTENTS
DEDICATION I
ACKNOWLEDGMENTS II
ABSTRACT III
LIST OF FIGURES VIII
LIST OF TABLES X
LIST OF ANNEXES XI
LIST OF ABBREVIATIONS XII
CHAPTER 1: INTRODUCTION 1
1.1 BACKGROUND 2
1.1.1 MODELS ON DRUG RESISTANCE AND EFFICACY 5
1. 2 RATIONALE OF THE STUDY 6
1.3 OBJECTIVE OF STUDY 7
1.3.1 PRIMARY OBJECTIVES 7
1.3.2 SECONDARY OBJECTIVES 8
1.3.3 MODELLING RESPONSE TO THERAPY AND PARASITE CLEARANCE TIME 8
1.4 SIGNIFICANCE OF STUDY 8
CHAPTER 2: LITERATURE REVIEW 9
2.1 HISTORY OF MALARIA 10
2.1.1 FROM MONO-THERAPY TO COMBINATION THERAPY 10
2.1.2. FIRST REPORT ON ARTEMISININ COMBINATION THERAPY RESISTANCE :...
12
2.2 EPIDEMIOLOGY OF MALARIA 13
2.2.1 HUMAN MALARIA PARASITES AND GEOGRAPHICAL DISTRIBUTION 13
2.2.2 LIFE CYCLE AND MODE OF TRANSMISSION 15
IV
2.2.3 TRANSMISSION AND ENDEMICITY 20
2.4 GENETIC DIVERSITY OF PIAMOSDIUM FALCIPARUM 22
2.4.1 IMMUNE PRESSURE AND EVASION OF P.FALCIPARURRIFROM 23
2.4.2 IMMUNOGENICITY 24
2.4.3 DRUG PRESSURE 24
2.5 MOLECULAR DIAGNOSIS/GENOTYPING OF PLASMODIUM FALCIPARUM 25
2.5.1 STRUCTURAL ORGANIZATION: CONSIDERATIONS AND IMPLICATIONS FOR
GENOTYPING 26
2.5.2. MOLECULAR PHYLOGENETIC AS A WAY TO PREDICT RESISTANCE PATTERNS OR
SPREAD.. 30
2.6 ANTI MALARIAL EFFICACY AND IN VITRO AND IN VIVO TESTS 31
2.7 FACTORS AFFECTING ANTI MALARIAL EFFICACY AND PARASITE CLEARANCE 33
2.7.1 HUMAN FACTORS (AGE, IMMUNITY) 33
2.7.2 THE IMPLICATION OF PHARMACOGENOMICS AND POLYMORPHISM: PRINCIPLES
35
2.7.3 ECOLOGICAL FACTORS (ETHNICITY, ENDEMICITY, CLIMATE) 37
2.7.4 PARASITE FACTORS (RESISTANT GENES, LIFE CYCLE) 39
CHAPTER 3: MATERIALS AND METHODS 47
3.1 RESEARCH DESIGN 48
3.1.1 STUDY POPULATION 48
3.1.2 STUDY PROCEDURE AND SAMPLING 50
3.1.3 ETHICAL CONSIDERATIONS 53
3.2 MOLECULAR ANALYSIS 54
3.2.1. EXTRACTION OF MALARIA PARASITE AND HUMAN DNA 54
3.2.2 PCR GENOTYPING OF PFMSP2 GENE (ADJUSTED CURE RATE TO DIFFERENTIATE
BETWEEN
RECRUDESCENCE AND REINFECTION) 55
3.2.3 AMPLIFICATION OF PFMDRGENE 57
3.2.4 RESTRICTION FRAGMENT LENGTH POLYMORPHISM (RFLP) ANALYSIS FOR
PFMDRL
MUTATION (N86Y) CONFERRING RESISTANCE 58
V
3.2.5 PCR GENOTYPING OF THE NAT-2 GENE 59
3.2.6 RESTRICTION FRAGMENT LENGTH POLYMORPHISM (RFLP) ANALYSIS FOR THE
NAT-2
GENE POLYMORPHISM 60
3.2.7 AGAROSE GEL ELECTROPHORESIS OF PCR PRODUCTS AND DIGESTS 62
3.3 DATA ANALYSIS AND MODELING 63
3.3.1 DATA MANAGEMENT 63
3.3.2 DESCRIPTIVE ANALYSIS OF PRIMARY OBJECTIVES 63
3.3.3 DESCRIPTIVE ANALYSIS OF SECONDARY OBJECTIVES 63
3.3.4 NON-INFERIORITY OF ASAQ AND DHP TO AL 64
3.3.5. EXPLORATIVE MULTIVARIATE MODELLING 64
-VARIABLE SELECTION 64
CHAPTER 4: RESULTS 69
4.1 PATIENT FLOW AND BASELINE CHARACTERISTICS 70
4.1.1 PATIENT FLOW 70
4.1.2 PATIENT BASELINE CHARACTERISTICS 71
4.2 DESCRIPTIVE ANALYSIS OF PRIMARY OBJECTIVES 71
4.2.1 EFFICACY 71
4.3 DESCRIPTIVE ANALYSIS OF SECONDARY OBJECTIVES 72
4.3.1 MOLECULAR ANALYSIS RESULTS 72
4.3.2 EFFICACY AND THERAPY OUTCOME ON DAY 14 AND 28 75
4.3.3 SAFETY OF THE THREE TREATMENT ARMS 76
4.4 NON INFERIORITY TESTING 77
4.5: PARASITE CLEARANCE TIME AND FEVER CLEARANCE TIME 77
4.5.1: PROPORTION OF PATIENTS WITH PARASITAEMIA WITH RESPECT TO TIME 77
4.5.2 PROPORTION OF PATIENTS WITH FEVER WITH RESPECT TO TIME 79
VI
4.6 MODELING TREATMENT OUTCOME AND DELAYANCE T O PARASITE CLEARANCE 79
4.6.1 EXPLORATORY DATA ANALYSIS 79
4.6.2 MULTIPLE LOGISTIC REGRESSION 81
4.5.1 EXPLORATORY DATA ANALYSIS USING KAPLAN MEIER SURVIVAL ESTIMATES 81
4.5.2 FITTING THE DISCRETE TIME SURVIVAL MODEL 85
4.5.3 DISCRETE TIME SURVIVAL MODEL DIAGNOSTICS 90
CHAPTER 5: DISCUSSION 91
CHAPTER 6: CONCLUSION AND RECOMMENDATION 97
6.1 CONCLUSION 98
6.2 RECOMMENDATION 98
REFERENCES 100
CURRICULUM VITAE 127
LIST OF PUBLICATIONS 128
VII
|
| any_adam_object | 1 |
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| dewey-ones | 610 - Medicine and health |
| dewey-raw | 610 |
| dewey-search | 610 |
| dewey-sort | 3610 |
| dewey-tens | 610 - Medicine and health |
| discipline | Medizin |
| format | Thesis Book |
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| physical | XIII, 128 S. Ill., graph. Darst. |
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| spelling | Mbuh Nji, Akindeh 1973- Verfasser (DE-588)1049270495 aut Modeling response and delayance to parasite clearance time to artemisinin combination therapies (ACT) von Akindeh Mbuh Nji 2013 XIII, 128 S. Ill., graph. Darst. txt rdacontent n rdamedia nc rdacarrier München, Univ., Diss., 2013 (DE-588)4113937-9 Hochschulschrift gnd-content Erscheint auch als Online-Ausgabe urn:nbn:de:bvb:19-168213 http://edoc.ub.uni-muenchen.de/16821/ Verlag kostenfrei Volltext https://nbn-resolving.org/urn:nbn:de:bvb:19-168213 Resolving-System DNB Datenaustausch application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=027204415&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis |
| spellingShingle | Mbuh Nji, Akindeh 1973- Modeling response and delayance to parasite clearance time to artemisinin combination therapies (ACT) |
| subject_GND | (DE-588)4113937-9 |
| title | Modeling response and delayance to parasite clearance time to artemisinin combination therapies (ACT) |
| title_auth | Modeling response and delayance to parasite clearance time to artemisinin combination therapies (ACT) |
| title_exact_search | Modeling response and delayance to parasite clearance time to artemisinin combination therapies (ACT) |
| title_full | Modeling response and delayance to parasite clearance time to artemisinin combination therapies (ACT) von Akindeh Mbuh Nji |
| title_fullStr | Modeling response and delayance to parasite clearance time to artemisinin combination therapies (ACT) von Akindeh Mbuh Nji |
| title_full_unstemmed | Modeling response and delayance to parasite clearance time to artemisinin combination therapies (ACT) von Akindeh Mbuh Nji |
| title_short | Modeling response and delayance to parasite clearance time to artemisinin combination therapies (ACT) |
| title_sort | modeling response and delayance to parasite clearance time to artemisinin combination therapies act |
| topic_facet | Hochschulschrift |
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