S. M. Niaz Arifin, PhD, is Research Assistant Professor in the Department of Computer Science and Engineering at the University of Notre Dame. A member of The Society for Computer Simulation and American Society of Tropical Medicine and Hygiene and the recipient of The American Society of Tropical Medicine and Hygiene Travel Award in 2011, his research interests include agent-based modeling and simulation, public health, data warehousing, and geographic information systems.

Gregory R. Madey, PhD, is Research Professor in the Department of Computer Science and Engineering at the University of Notre Dame. A member of The Society for Computer Simulation, Institute of Electrical and Electronics Engineers Computer Society, and American Society of Tropical Medicine and Hygiene, his research interests include agent-based modeling and simulation, cyberinfrastructure, bioinformatics, biocomplexity, e-Technologies, open source software, disaster management, and health informatics.

Frank H. Collins, PhD, is Professor in the Department of Biological Sciences at the University of Notre Dame. His research interests include genome level studies of arthropod vectors of human pathogens, the biology of malaria vectors with a focus on the development of molecular tools that will permit better resolution of questions about vector population ecology, ecological genetics, and the epidemiology of malaria transmission.

List of Contributors xv

List of Figures xvii

List of Tables xxi

Preface xxiii

Acknowledgements xxix

List of Abbreviations xxxi

1 Introduction 1

1.1 Overview 1

1.2 Malaria 3

1.3 Agent-Based Modeling of Malaria 4

1.4 Contributions 4

1.5 Organization 5

2 Malaria: A Brief History 7

2.1 Overview 7

2.2 Malaria in Human History 7

2.2.1 The Malarial Path: Ancient Origins 8

2.2.2 Naming and Key Discoveries 9

2.2.3 Antimalarial Drugs 9

2.2.4 Prevention Measures 10

2.3 Malaria Epidemiology: A Global View 10

2.3.1 The Malaria Parasite 11

2.3.2 Geographic Distribution 12

2.3.3 Types of Transmission 12

2.3.4 Risk Mapping and Forecasting 13

2.4 Malaria Control 13

3 Agent-Based Modeling and Malaria 17

3.1 Overview 17

3.2 Agent-Based Models (ABMs) 17

3.2.1 Agents 18

3.2.2 Environment 19

3.2.3 Rules 20

3.2.4 Software for ABMs 20

3.3 History and Applications 21

3.3.1 M&S Organizations 21

3.4 Advantages of ABMs 23

3.4.1 Emergence, Aggregation, and Complexity 23

3.4.2 Heterogeneity 24

3.4.3 Learning and Adaptation 24

3.4.4 Flexibility in System Description 24

3.4.5 Inclusion of Multiple Spaces 25

3.4.6 Limitations of ABMs 25

3.4.7 ABMs vs Mathematical Models 27

3.4.8 Applicability of ABMs for Malaria Modeling 28

3.5 Malaria Models: A Review 29

3.5.1 Mathematical Models of Malaria 30

3.5.2 Agent-Based Models (ABMs) of Malaria 33

3.5.3 The Spatial Dimension of Malaria Models 35

3.6 Summary 36

4 The Biological Core Model 39

4.1 Overview 39

4.1.1 Relevant Terms of Interest 40

4.2 The Aquatic Phase 41

4.2.1 Egg (E) 42

4.2.2 Larva (L) 43

4.2.3 Pupa (P) 45

4.3 The Adult Phase 46

4.3.1 Immature Adult (IA) 46

4.3.2 Mate Seeking (MS) 47

4.3.3 Blood Meal Seeking (BMS) 47

4.3.4 Blood Meal Digesting (BMD) 47

4.3.5 Gravid (G) 47

4.4 Aquatic Habitats and Oviposition 48

4.4.1 Aquatic Habitats 48

4.4.2 Oviposition 48

4.5 Senescence and Mortality Rates 50

4.5.1 Senescence 50

4.5.2 Mortality Models: Basic Mathematical Formulation 51

4.6 Mortality in the Core Model 51

4.6.1 Aquatic (Immature) Mortality Rates 52

4.6.2 Adult Mortality Rates 53

4.7 Discussion 53

4.7.1 An Extendible Framework for Other Anopheline Species 53

4.7.2 Weather, Seasonality, and Other Factors 54

4.7.3 Mortality Rates 54

4.8 Summary 54

5 The Agent-Based Model (ABM) 57

5.1 Overview 57

5.2 Model Architecture 58

5.2.1 Object-Oriented Programming (OOP) Terminology 58

5.2.2 Agents 60

5.2.3 Environments 62

5.2.4 Event-Action-List Diagram 62

5.3 Mosquito Population Dynamics 64

5.4 Model Features 66

5.4.1 Processing Steps Ordering 66

5.4.2 Model Assumptions 67

5.4.3 Simulations 69

5.5 Summary 69

6 The Spatial ABM 71

6.1 Overview 71

6.2 The Spatial ABM 74

6.2.1 Definition of Terms 74

6.2.2 Landscapes 75

6.2.3 Landscape Generator Tools 76

6.3 Resource Clustering 79

6.4 Flight Heuristics for Mosquito Agents 81

6.5 Simulation Results 85

6.5.1 Model Verification 85

6.5.2 Landscape Patterns 86

6.5.3 Relative Sizes of Resources 87

6.5.4 Resource Density 88

6.5.5 Combined Habitat Capacity (CHC) 89

6.6 Spatial Heterogeneity 90

6.7 Summary 93

7 Verification, Validation, Replication, and Reproducibility 95

7.1 Overview 95

7.2 Verification and Validation (V&V): A Review 96

7.2.1 Acceptability Assessment and Quality Assurance (QA) 96

7.2.2 Verification and Validation (V&V) 98

7.3 Replication and Reproducibility (R&R): A Review 100

7.4 Summary 101

8 Verification and Validation (V&V) of ABMs 103

8.1 Overview 103

8.2 Verification and Validation (V&V) of ABMs 103

8.3 Phase-Wise Docking 105

8.3.1 Assumptions for the ABMs 105

8.3.2 Phase-Wise Docking Results 107

8.4 Compartmental Docking 110

8.4.1 Implementations of the ABMs 111

8.4.2 Assumptions for the ABMs 112

8.4.3 Compartmental Docking Results 114

8.5 Summary 116

9 Replication and Reproducibility (R&R) of ABMs 121

9.1 Overview 121

9.1.1 Simulation Stochasticity 122

9.1.2 Boundary Types 123

9.2 Vector Control Interventions 124

9.2.1 Larval Source Management (LSM) 125

9.2.2 Insecticide-Treated Nets (ITNs) 126

9.2.3 Population Profiles for ITNs 127

9.2.4 Coverage Schemes for ITNs 127

9.2.5 Applying LSM in Isolation 130

9.2.6 Applying ITNs in Isolation 132

9.2.7 Applying LSM and ITNs in Combination 132

9.3 Simulation Results 134

9.3.1 Simulation Stochasticity 134

9.3.2 LSM in Isolation 134

9.3.3 Impact of Boundary Types 137

9.3.4 ITNs in Isolation 138

9.3.5 LSM and ITNs in Combination 143

9.4 Replication and Reproducibility (R&R) Guidelines 147

9.5 Discussion 150

9.6 Summary 152

10 A Landscape Epidemiology Modeling Framework 155

10.1 Overview 155

10.2 GIS in Public Health 159

10.3 The Study Area and the ABM 160

10.3.1 Features of the Spatial ABM 161

10.3.2 Vector Control Intervention Scenarios 162

10.4 The Geographic Information System (GIS) 163

10.4.1 The GIS-ABM Workflow 163

10.4.2 GIS Processing of Data Layers 164

10.4.3 Feature Counts 165

10.5 Simulations and Spatial Analyses 165

10.5.1 Output Indices 166

10.5.2 Hot Spot Analysis 167

10.5.3 Kriging Analysis 167

10.6 Results 168

10.6.1 Mosquito Abundance 168

10.6.2 Oviposition Count per Aquatic Habitat 171

10.6.3 Blood Meal Count per House 174

10.7 Discussion 177

10.7.1 Stochasticity and Initial Conditions 177

10.7.2 Model Calibration and Parameterization 178

10.7.3 Emergence 178

10.7.4 Complexity 179

10.7.5 Data Resolution (Granularity) 179

10.7.6 Spatial Analyses 180

10.7.7 Habitat-based Interventions 181

10.7.8 Miscellaneous Issues 181

10.8 Conclusions 182

11 The EMOD Individual-Based Model 185
Philip A. Eckhoff and Edward A. Wenger

11.1 Overview 185

11.1.1 Motivation: Modeling of Malaria Eradication 186

11.1.2 Questions that Arise in the Context of Malaria Eradication 187

11.1.3 Spatial Heterogeneity and Metapopulation Effects 188

11.1.4 Implications for Model Structure 190

11.2 Model Structure 193

11.2.1 Human Demographics and Synthetic Population 193

11.2.2 Vector Ecology 194

11.2.3 Vector Transmission 195

11.2.4 Within-Host Disease Dynamics 197

11.2.5 Human Migration and Spatial Effects 198

11.2.6 Stochastic Ensembles 200

11.3 Results 201

11.3.1 Single-Village Simulations 201

11.3.2 Spatial Simulations: Garki District 202

11.3.3 Madagascar 203

11.4 Discussion 206

Appendix A Enzyme Kinetics Model for Vector Growth and Development 209

A.1 Overview 209

A.2 Stochastic Thermodynamic Models 210

A.3 Poikilothermic Development Models 210

A.4 The Sharpe and DeMichele Model 214

A.5 The Schoolfield et al. Model 217

A.6 Depinay et al. Model 219

A.7 Summary 221

Appendix B Flowchart for the ABM 223

B.1 Flowchart for the Agent-Based Model (ABM) 223

Appendix C Additional Files for Chapter 10 233

Appendix D A Postsimulation Analysis Module for Agent-Based Models 239

D.1 Overview 239

D.2 Simulation Output Analysis: A Review 240

D.3 The LiNK Model 243

D.4 P-SAM Architecture 245

D.5 Postsimulation Analysis and Visualization 247

D.6 P-SAM Performance 250

D.7 Conclusion 254

References 255

Index 279

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