Preface 4
Contents 5
Contributors 7
Part I Introduction into Kala-Azar 10
1 Geographical Distribution of Kala-Azar in South Asia 11
1.1 Global and Regional Situation 12
1.2 Kala-Azar in Bangladesh 14
References 17
2 Pathology and Mechanism of Disease in Kala-Azar and Post-kala-azar Dermal Leishmaniasis 18
2.1 Life Cycle of Leishmania Donovani and Mode of Transmission of Kala-Azar 18
2.1.1 Life Cycle in Human Host 19
2.1.2 Life Cycle in Sandfly 19
2.2 Pathogenesis and Pathophysiology of Kala-Azar 20
2.3 Clinical Presentation of Kala-Azar 21
2.4 Clinical Presentation of PKDL 21
References 21
3 Diagnosis and Treatment of Kala-Azar and Post-kala-azar Dermal Leishmaniasis 22
3.1 Diagnosis of Kala-Azar 23
3.2 Diagnosis of Post-kala-azar Dermal Leishmaniasis 23
3.3 Treatment of Kala-Azar 23
3.4 Treatment of PKDL 24
References 25
Part II Therapeutic Strategy to Deal with Emergence of Drug Resistance 26
4 Epidemiology of Drug-Resistant Kala-Azar in India and Neighboring Countries 27
4.1 Introduction 28
4.1.1 History of Kala-Azar on the Indian Subcontinent 28
4.1.2 Incidence of Kala-Azar in Bangladesh 29
4.1.3 Incidence of Kala-Azar in Nepal 29
4.1.4 The Current Scenario on the Indian Subcontinent 30
4.2 History of the Efficacy of Antileishmanial Drugs on the Indian Subcontinent 31
4.2.1 Sodium Stibogluconate (SSG) Resistance in Nepal 31
4.2.2 Efficacy of Miltefosine in Nepal 31
4.2.3 Efficacy of SSG in Bangladesh 31
4.2.4 Changing Response to Different Antileishmanial Agents in India 32
4.2.5 Changing Response to Diamidine Compounds 33
4.2.6 Amphotericin B 35
4.2.7 Liposomal Amphotericin B (AmBisome) 35
4.2.8 Paromomycin (Aminosidine) 36
4.2.9 Status of Oral Treatments for Kala-Azar 36
4.2.10 Miltefosine as a Treatment for Kala-Azar 36
4.2.11 Sitamaquin (WR 6026) 37
4.3 Combination Therapy for Indian Kala-Azar 37
4.4 Combination Therapy in Kala-Azar Associated with HIV/AIDS 37
4.5 Conclusion 38
References 38
5 A Therapeutic Strategy for Treating Visceral Leishmaniasis in Regions with Drug Resistance 41
5.1 Introduction 42
5.2 Antileishmanial Drugs 42
5.2.1 Sodium Stibogluconate 42
5.2.2 Amphotericin B 43
5.2.3 Liposomal Drug Delivery System 43
5.2.4 Paromomycin 44
5.2.5 Miltefosine 45
5.3 Regulations and Policy 45
5.4 Prevention of Drug Resistance 46
5.5 Rationale for Combination Chemotherapy 46
5.6 Pharmacological Considerations for Combination Therapy 47
5.7 Compliance with Treatment 48
5.8 Response to Treatment in AIDS-Related Kala-Azar 48
5.9 Conclusion 49
References 49
6 Combination Therapy for Leishmaniases 53
6.1 Introduction 54
6.2 Drugs Currently in Use 55
6.2.1 Pentavalent Antimonials 55
6.2.2 Ampho B 55
6.2.3 LamB 55
6.2.4 Paromomycin 56
6.2.5 Miltefosine 57
6.3 Combination Therapies 57
6.4 Future Trends for the Treatment of Leishmaniases 59
6.5 Recommendation 61
References 61
Part III Diagnostic Strategy Enhancing KalaAzar Elimination Program 63
7 Challenges in the Diagnosis of Visceral Leishmaniasis on the Indian Subcontinent 64
7.1 Introduction 65
7.2 Diagnostic Tests for VL 65
7.2.1 Nonspecific Tests 66
7.2.2 Parasite Detection 66
7.2.3 Serological Tests 66
7.2.4 Antigen Detection Tests 68
7.3 Access to VL Care 68
7.4 Issues in the Use of the RDT in the Field 69
7.5 Conclusion 70
References 70
8 The Potential of Urinary Tests in the Management of Kala-Azar 73
8.1 Introduction 74
8.2 Physiological and Pathophysiological Attributes of FABP1 in the Human Kidney 75
8.3 Potential of FABP1 as a Urinary Diagnostic Tool in Kala-Azar 80
8.4 Efficacy of Detecting Renal Toxicity by Urinary FABP1 82
8.5 Development of the Immunochromatography (Dipstick) Method for Measuring FABP1 85
8.6 IL-18 as Another Potential Urinary Biomarker in Kala-Azar 88
8.7 Future Prospects of Urinary Biomarker Use in Kala-Azar 91
References 92
9 Mass-Survey Using Urine and Confirmation by LAMP for Control of Visceral Leishmaniasis 95
9.1 Introduction 95
9.2 Mass Survey of VL Using Urine 96
9.3 Confirmation of VL Using LAMP 97
9.4 Combination of the Urine ELISA and LAMP 100
9.5 Conclusion 100
References 100
Part IV PKDL and Its Implications in Eliminating KalaAzar 103
10 Polymorphism of Leishmaniasis Caused by Leishmania donovani Sensu Lato in Asia 104
10.1 Polymorphic Leishmaniasis 105
10.2 Pathogenesis of Leishmaniasis 106
10.3 KA in Asia 107
10.4 Post-kala-azar Dermal Leishmaniasis in Asia 107
10.5 CL Caused by L. donovani 110
10.6 Working Toward the Control of VL 111
References 112
11 Post-kala-azar Dermal Leishmaniasis: Facing the Challenge of Eliminating Kala-Azar from South Asia 114
11.1 Clinical Features 115
11.2 Epidemiology 117
11.3 Diagnosis 117
11.4 Histopathology 119
11.5 Treatment 119
11.6 Pathogenesis 121
11.7 Challenges for VL Elimination 122
11.8 Methods and Strategies to Control PKDL 123
References 125
Part V New Challenges Confronting Kala Azar Elimination Programme and Their Possible Solutions 128
12 Climate Change and Kala-Azar 129
12.1 Background 130
12.2 The Regional Impact of Climate Change 131
12.3 Climate Change and the Spatio-Temporal Distributions of Leishmaniasis 131
12.4 Leishmaniasis and Other Vector-Borne Diseases 132
12.5 Temperature Rise, Flooding, Sanitation, and Health Impacts 132
12.6 Sea-Level Rise and Its Impact on Health 133
12.7 Climate Change and Livelihood 134
12.8 What Should SEAR Countries Do About Climate Change 135
12.9 Conclusion 136
Appendix: What Can We as Individuals Do to Help Reduce the Adverse Health Impact of Climate Change? 137
References 138
13 The Role of Policy Makers in Achieving the Target for Kala-Azar Elimination in South Asia: The Bangladesh Experience 140
13.1 Introduction 141
13.2 The \ 141
13.3 Implementation of the \ 142
13.4 The Rise and Fall of Miltefosine in Bangladesh 143
13.5 The Need for a Quality Assurance Program for Drugs 143
13.6 Partnerships for Utilizing All Available Resources 143
13.7 Improving Surveillance of Kala-Azar and Post-kala-azar Dermal Leishmaniasis 144
13.8 Strengthening Vector Control Programs 144
13.9 Future Directions for Basic and Operational Research on Kala-Azar 144
13.10 Conclusion 145
References 145
Index 147