Experimental infection and protection against ... - TI Pharma

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Comparison of clinical and parasitological data from experimental human malaria challenge trials Figure 4. Correlation of Q-PCR parasitemia with prepatent period Correlation between peak parasitemia (A) or geometric mean parasitemia during the first multiplication cycle from day 6.5 to day 8.5 (B) with prepatent period (R 2 = 0.27 and -0.73, p=0.006 and p=
110 Chapter 5 in time to microscopically detected parasitemia whereas clinical symptoms are broadly similar. Although there are several methodological differences between the CHMI protocols that limit direct comparability, this difference in prepatency likely results from variation in the mean parasite burden in the first blood stage, possibly as a result of different inoculum size, whilst blood stage multiplication factors are equal. The analysis of adverse events from 175 non-immune participants of sporozoite challenge trials shows that serious adverse events (grade 4) are rare. One serious cardiac adverse event was reported; the true nature and pathophysiological explanation of that event remains unclear [21]. Severe adverse events (grade 3) related to clinical malaria occur in up to half of the volunteers and persist for several days. We conclude that CHMI are generally safe, but may lead to severe (grade 3) symptoms, though not serious adverse events, in a significant proportion of subjects. Several precautions are taken in both institutions to ensure safety of volunteers, such as 24-hour phone access, medicalert cards and emergency contact procedures. Nevertheless, the exposure of volunteers to the likelihood of some severe adverse events should be carefully weighed against the benefits of the information to be gained [22]. We find significant differences in frequencies of fever, fatigue, arthralgia and chills between institutions. Cohorts with a longer prepatent period or a higher peak parasitemia do not consistently show a higher frequency of adverse events. These data, combined with methodological differences in the recording of adverse events (e.g. home-monitoring of oral temperature in RUNMC), lead us to conclude that biologically relevant variation in patho-physiology between institutions seems unlikely. Nevertheless, standardized assessment of adverse events and harmonization of solicited events would advance the interpretability and comparability of CHMI in different settings worldwide. Laboratory safety parameters show a severe decrease in platelet count (
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Experimental infection and protecti
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Experimental infection and protecti
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Contents Contents 5 Chapter 1 - Int
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Introduction 9 Malaria Malaria is o
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Introduction 11 Preclinical Clinica
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Introduction 13 pipeline of clinica
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Introduction 15 The division of ant
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Introduction 17 Figure 4. Populatio
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Introduction 19 candidates. Initial
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Introduction 21 - to identify param
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Introduction 23 20. Nussenzweig RS,
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Introduction 25 50. Ouedraogo AL, R
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Introduction 27 RTS,S/AS02 in malar
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Chapter 2 Safety and Immunogenicity
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Safety and Immunogenicity of a Reco
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Chapter 3 Humoral immune responses
Page 60 and 61: Humoral immune responses to a singl
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Page 83 and 84: Chapter 4 82 Abstract The functiona
Page 85 and 86: 84 Chapter 4 Figure 1. Schematic re
Page 87 and 88: 86 Chapter 4 Concentration (mg/ml,
Page 89 and 90: 88 Chapter 4 Figure 4: Correlation
Page 91 and 92: 90 Chapter 4 positively correlated
Page 93 and 94: 92 Chapter 4 Acknowledgements The a
Page 95 and 96: 94 Chapter 4 determinant of subsequ
Page 98 and 99: Chapter 5 Comparison of clinical an
Page 100 and 101: Comparison of clinical and parasito
Page 118 and 119: Chapter 6 Efficacy of pre-erythrocy
Page 120 and 121: Efficacy of pre-erythrocytic and bl
Page 130 and 131: Chapter 7 NF135.C10: a new Plasmodi
Page 132 and 133: NF135.C10: a new Plasmodium falcipa
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Page 154 and 155: Induction of malaria in volunteers
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Induction of malaria in volunteers
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Section 3 Whole parasite inoculatio
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174 Chapter 9 Abstract An effective
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176 Chapter 9 Figure 1. Study desig
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178 Chapter 9 followed by five iden
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180 Chapter 9 Figure 2. Parasitemia
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182 Chapter 9 Test Day I-1 Day C-1
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184 Chapter 9 strain P. falciparum-
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186 Chapter 9 protective role in ot
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188 Chapter 9 References 1. Greenwo
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190 Chapter 9 27. Orjih AU. Acute m
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192 Chapter 9 medium A (Caltag Labo
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194 Chapter 10 Abstract Induction o
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196 Chapter 10 Pre-erythrocytic sta
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198 Chapter 10 procedures described
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200 Chapter 10 by hand-dissection.
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202 Chapter 10 Figure 3. Mean numbe
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204 Chapter 10 Figure 4. Number of
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206 Chapter 10 temperature (Pearson
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208 Chapter 10 immune modulating ef
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210 Chapter 10 cytokine measurement
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212 Chapter 10 14. Hermsen CC, Telg
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Chapter 11 General Discussion
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General Discussion 217 occurrence o
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General Discussion 219 mediating th
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General Discussion 221 AMA1 express
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General Discussion 223 troponins ca
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General Discussion 225 and between
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General Discussion 227 immunologica
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General Discussion 229 to induce pr
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General Discussion 231 Conclusions
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General Discussion 233 References 1
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General Discussion 235 polymorphonu
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General Discussion 237 57. Church L
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General Discussion 239 85. Beier JC
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General Discussion 241 118. Mueller
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Chapter 12 Summary Samenvatting Lis
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246 Chapter 12 Controlled human mal
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Summary, Samenvatting, List of publ
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254 Chapter 12 Roestenberg M, Teirl
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