Textbook of Pediatric Infectious Diseases Vijay N Yewale, Digant D Shastri, Abhay K Shah, Kheya Ghosh Uttam, Ritabrata Kundu, Jaydeep Choudhury, Dhanya Dharmapalan, A Parthasarathy, Shyam Kukreja, Ashok Rai, Sanjay Krishna Ghorpade, Vasant Khalatkar
INDEX
Page numbers followed by, b refer to box, f refer to figure, fc refer to flowchart, and t refer to table.
A
Abacavir 374, 375, 377, 378, 612
Abscess 248, 267
amebic 411
cutaneous 439
formation 443, 555
parapharyngeal 164
peritoneal 219
peritonsillar 164
renal 435
retropharyngeal 157, 164
subdiaphragmatic 220f
subphrenic 219
Absolute neutrophil count 70, 106, 125
Acellular pertussis 471, 499
vaccine 488, 491, 494, 504, 517
Acholeplasma 266
Acid-base imbalances 638
Acid-fast bacilli 48f, 272, 283, 284
Acidosis 183
lactic 378
metabolic 216, 355, 361, 362, 384
Acinetobacter 109, 135, 215
baumannii 51, 62
Acquired immunodeficiency syndrome 12, 12t, 18, 206, 371, 515
Actinomycetemcomitans 189
Acyclovir 315, 316, 325, 603
Adenitis 548
mesenteric 213
Adenosine monophosphate, cyclic 262
Adenovirus 80, 157, 158, 161, 206, 267, 289, 310
Adolescent Friendly Health Services in India 552
Adult respiratory distress syndrome 422
Adverse drug reactions, severe cutaneous 86
Adverse event
following immunization 482
immunization, types of 483t
Adverse reactions following vaccination 346
Advisory Committee on Immunization Practices 326, 345
Aedes aegypti 306, 349, 349f, 364
Aedes albopictus 348
Agglutination tests 53, 433
Air
control parameters 40
ventilation 40
Airborne
infections 431
precautions 41
Alanine aminotransferase 352
Albendazole 404, 407
Albert stain 47
Alcohol 462
Allergic bronchopulmonary aspergillosis 275, 393
Allergic reactions, severe 483
Allopurinol 86, 450
Alpha hemolytic streptococci 188
Alpha herpesvirus 323
Aluminum adjuvanted vaccines 500
Alveolar lavage, nonbronchoscopic 113
Amantadine 603
Amastigote 451
Amebiasis 410
pleuropulmonary 411, 414
Amebic colitis
chronic 410
complications of 413
fulminant 410
American Academy of Pediatrics 329
American Heart Association 132
American Thoracic Society 115
Amikacin 237, 574
Aminoglycosides 3336, 63, 68, 70, 97, 153, 217
Aminosidine 449
Amorolfine 631
Amoxicillin 35, 82, 106, 131133, 148, 160, 163, 170, 171, 199, 574, 583
Amphotericin B 126, 389, 448
Ampicillin 82, 131133, 148, 153, 170, 177, 248, 369, 456, 574
Amplification techniques 56
Amprenavir 375
Anaerobic infections 438, 439
diagnosis of 440
treatment of 440
Anaphylaxis, emergency management of 483b
Ancylostoma duodenale 407
Anemia 147, 295, 321, 378, 382, 423, 447
aplastic 308, 425
chronic 319
congenital 319
hemolytic 198, 267, 269
mild 412
persistent 319
severe normocytic 384
Angular cheilitis 372
Animal bite wounds, management of 462
Ankle joint 546
Annular petechial rash 353f
Anorexia 242
Anthrax 525
Antibiogram 198
Antibiotic 29, 31, 33, 160, 244, 264, 330, 488, 574
coated catheters 118
cycling 44
effect 35
fails 31
mechanism of action of 33
parenteral 217
postexposure 258
prophylaxis 128, 131
resistance
etiology of 43
multiple 36
prevention of 43
selection of 170
principles of 34
sensitive enteric gram-negative bacilli 116
therapy 36, 128, 160t, 162, 240
duration of 98
empirical 176
indications of 36
intravenous 170
treatment 191
duration of 245
Antibody 469
deficiencies 106
detection 388, 447
test 411
Anticonvulsants 86
Anti-Epstein-Barr nuclear antigens 368
Antifungals
agent 448
role of 126
systemic 230, 232
Antigen
complexes 485
detection tests 244, 456
presenting cells 473
Antihelminthics 86
Antileprosy drugs, dosage of 285t
Antimeasles antibody 290
Antimicrobial
agent 33, 435
eye 628
prophylaxis 128, 200
resistance, dynamics of 43
sensitivity testing 454
susceptibility testing 51
therapy 44, 51, 434, 456
empirical 96
pathogen-specific 177
treatment 73, 160
use of 212
Antinuclear antibody 311
Antipseudomonal beta-lactam agent 106
Antirabies
antibody, protective level of 464
vaccines 464
Antiretroviral drugs 374, 378, 612
new classes of 375
Antiretroviral therapy 134, 146, 371, 372, 374, 376378
adverse effects of 378
response of 378
Antirickettsial therapy 423
Antiseptic, application of 462
Anti-smooth muscle antibody 311
Antitoxin, doses of 252t
Antituberculosis treatment, principles of 277b
Antituberculous drug 596
Antiviral
agents 330
capsid antigens 368
drugs 106
role of 126
therapy 185, 488
Aphasia 243
Aplastic crisis, transient 319, 321
Apnea 329
Appendicitis 98, 236
Aqueductal stenosis 298
Arboviruses 181
infection 181
Arrhythmias, cardiac 260
Artemisinin 599
Arterial blood gases, monitoring of 361
Artery
disease, coronary 337
hypoplasia, pulmonary 142
Artesunate 599
Arthralgia 267, 294, 321, 547
Arthritis 85, 238, 267, 296, 321, 396
autoimmune 213
dermatitis syndrome 239
juvenile
idiopathic 369, 545
rheumatoid 239
monoarticular 432
peripheral 434
reactive 238, 239
rheumatoid 320
Arthropathy 147, 320
Arthropod borne viruses 180
Ascaris lumbricoides 404
treatment of 404t
Asexual blood-stage vaccine 526
Aspartate aminotransferase 308, 352, 449
Aspergillus 103, 104, 189
fumigatus 103
Aspiration 253, 412
cytology 273
pneumonia 144, 168
Asteroloplasma 266
Asthma 337
exacerbations of 269, 328
Atazanavir 375
Atelectasis 275
Auditory defects 295
Auto-disable syringes 570, 570f
Autoimmune diseases 320, 545
Autoimmune disorders 434, 534
Automatic voltage stabilizer 538
Axillary hairs 222f
Axiom 220
Azithromycin 132, 135, 163, 245, 268, 398, 425, 457, 556, 575
Azotemia 427
Aztreonam 65, 66, 217, 245, 457, 575
B
Bacillary index 284
Bacilli
bordetella pertussis 256
gram-negative 102, 438
gram-positive 438
Bacillus anthracis 39, 534
Bacillus calmette-guérin 6, 130, 280, 451, 471, 483, 484, 500, 536, 538
vaccine 501, 515
Bacillus cereus 207
Backache 314
Baclofen 260
Bacteremia 68, 91, 106, 149, 189, 206, 248, 440, 443
causes of 73t
complications of 440
occult 73, 75
pneumococcal 75
staphylococcal 33
Bacteria 48, 167, 207, 238
gram-negative 240
gram-positive 105
morphology of 48f
Bacterial culture, main limitation of 50
Bacterial diseases 423
Bacterial infection 31, 36, 69, 159t, 241, 553
acute 256
circumstantial evidence of 29
management of 33
recurrent severe presumed 372
serious 75
Bacterial meningitis 174, 177, 177t
complications 178
diagnosis 175
etiology 174
management 176
pathogenesis 174
prevention 179
Bacterial peritonitis, primary 98
Bacterial pneumonia, severe recurrent 372
Bacteriological index 281
Bacteriological media, types of 49
Bacteriuria 195
asymptomatic 195, 201
catheter associated 122
Bacteroides 234, 438
fragilis 49, 438
oralis 438
Barking cough 165
Basophils 102
Bat rabies 461
B-cell 472
defects 103, 107
Beef tapeworm 408
Behçet disease 545
Benzathine penicillin 132, 160, 252, 576
intramuscular 129
Benzoin 557
Benzylpenicillin 576, 591
Best injection techniques 565
Beta-lactam antibiotics 33, 35, 86, 193, 236
Beta-lactamase 62
classification of 62t
inhibitor combinations 68
producers 212
Bichloroacetic acid 557
Bilirubin, fractionation of 308
Bilophila 438
Biodegradable micro-and nano-particle vaccines 529
Bird flu 333
Bismuth sulfite 248
Black measles 289
Bladder dysfunction 302
Blastocystis hominis 206
Blastomyces dermatitidis 394
Blastomycosis 394
mild pulmonary 395
Bleachable erythematous flush 353f
Bleeding
conjunctival 354
diathesis 348
Blindness 137
Blood
agar 454
borne defection 46
crusts 222
culture 94, 176, 189, 243, 454
disorders 337
eosinophilia, peripheral 398
glucose disturbances 362
pressure, systolic 91t
stained cloths 222
tests, basic 308
Bloodstream infection
catheter related 108, 116
central line related 116
Blueberry muffin lesions 295
Body fluid cytology 273
Body louse infestation 222
Bone 248
and joint infection 233, 237t
fractures 260
infection, pediatric 237t
lesions, radiolucent 296
marrow 121
aspiration culture 243
culture 454
suppression 378
transplantation 104, 325
necrosis 238
pain 234
scan 235
tumors, primary 236
Borderline lepromatous 283
leprosy 283, 283f
Borderline tuberculoid 283
leprosy 282
Bordetella 49
pertussis 130, 256
infection 529
mutant strain 529
Borrelia burgdorferi 183, 239
Botulinum toxins 443
Botulism 443
differential diagnosis 444
pathogenesis 443
prognosis 445
treatment 444
Bowel bladder dysfunction 200
Bowel diseases, parasitic 404
Bradycardia 91t
Brain
abscess 413
hypoxemia 183
Brainstem encephalitis 444
Breastfeeding 213, 371
Breath, shortness of 335
British Human Immunodeficiency Virus Association 134
Broad-spectrum antimicrobial agents 153
Brodie abscess 234, 236
Bronchiectasis 271
Bronchiolitis 329, 330
acute 327
moderate 330
obliterans 267
obliterative organizing pneumonia 275
Bronchitis
chronic 269
wheezy 328, 329
Bronchoalveolar lavage 113, 275
Bronchodilators 330
Bronchopneumonia 400
Brown dog tick 421f
Brucella 53, 104
abortus 430
canis 430
infection 430
culture 432
diagnosis 432
epidemiology 430
etiology 430
pathogenesis 431
treatment 434
melitensis 430
suis 430
Brucellosis 310, 430
etiology of 430t
treatment of 435t
Brudzinski sign 301
Bulbar palsy 144
Bulbar polio 301, 302
Bulbospinal polio 301
Bull neck 250
Bullous impetigo 224f
Bunyaviruses 180
Burkholderia cepacia 103
Burkitt lymphoma 368
Burns 101
Bush-Jacoby-Medeiros system 62
Butcher's wart 227
Butenafine 230
Butoconazole 557
C
Calcium gluconate 639
Calymmatobacterium granulomatis 553
Campylobacter 207, 208, 212, 213, 239
jejuni 206
Cancer
cervix uteri 5
chemotherapy 104
vaccines 534
Candida 119, 121
albicans 102, 103, 133, 189, 215, 394, 395, 553, 554
antigen despite chronic infection 103
endocrinopathy syndrome 395
pneumoniae 396
Candidemia 126
Candidiasis 133, 395
disseminated 396
Candiduria 397
Cantharidin 228
Capillaria philippinensis 407
Carbapenems 34, 6769, 106, 109, 217, 237, 576
Carbohydrates 536
Carcinoma 411
cervix 479f
hepatocellular 305
nasopharyngeal 368
Cardiobacterium hominis 189
Cardiomyopathy 378
Cardiovascular system 295
Caspofungin 126
Cat scratch disease 434
Cataract 294296
Catch-up vaccination 254, 491, 519, 519t
Catecholamines, levels of 181
Catheter, types of 118
Cefaclor 131, 163, 171, 577
Cefadroxil 131, 132, 224, 577
Cefazolin 132, 165
Cefdinir 163, 171, 198, 577
Cefepime 106, 177, 578
Cefixime 131, 198, 224, 244, 578
Cefoperazone 217, 457, 579
Cefotaxime 65, 66, 154, 177, 217, 237, 457, 579
Cefoxitin 557
Cefpodoxime 65, 66, 163, 170, 171, 244, 579
Ceftaroline fosamil 59
Ceftazidime 34, 6466, 106, 135, 177, 580
Ceftizoxime 557
Ceftriaxone 65, 66, 97, 129, 154, 177, 237, 245, 457, 556, 557, 580
parenteral 35
Cefuroxime 163, 165, 170, 171, 237, 580
Cell
migration 102
mononuclear 560
phagocytic 431
producing interferon 451
Cellular vaccine candidates 529
Cellulitis 106, 224, 225f
legs 225f
Centers for Disease Control and Prevention 258, 297, 322
Central nervous system 93, 143, 151, 178, 180, 295, 267, 300, 314, 352, 398, 441, 547, 635
disease 269
infection 183, 248, 316, 438, 635
toxoplasmosis 373
Central venous catheters, non-tunneled 116
Cephalexin 131, 132, 171, 237, 581
Cephalic tetanus 259, 441
Cephalosporins 33, 62, 63, 68, 170, 457, 581
second-generation 34
third-generation 34, 128, 236
Cephamycins 109
Cerebellar
ataxia 85, 243, 267, 298
hypoplasias 138
Cerebellum, dysfunction of 420
Cerebral
amebiasis 414
imaging 398
infarction 185
malaria 183
thrombophlebitis 290
thrombosis 243
Cerebrospinal fluid 47, 68, 81, 94, 101, 129, 151, 181, 243, 268, 272, 298, 301, 302, 314, 397, 633
abnormal 73
analysis 184
examination 175, 301, 315
shunts 101
transport 175
Cervical
intraepithelial neoplasia 343, 344
lymphadenitis 289
Cervix, uncomplicated gonococcal infections of 556
Cetrimide solution 462
Chancroid 556
Chart recorders 541
Chediak-Higashi syndrome 103, 107
Chemoprophylaxis 254, 280, 280fc
Chemotherapy 325
Chest
pain 267
radiography 183
roentgenograph 274
X-ray 267, 335
Chick embryo cell vaccine, purified 465, 511
Chickenpox 84, 87f, 100, 323, 324, 326, 516
Chikungunya 136, 364, 365
fever 13, 20, 364, 366t
infection 365f
vaccines 531
virus 364
Chills 335
Chimeric live attenuated vaccines 530
Chimpanzee coryza virus 327
Chinese hamster ovary cells 464
Chlamydia 53, 169, 269
pneumoniae 167, 266, 401
infection 267
psittaci 266
trachomatis 150, 257, 554556
pneumonia 401
Chlamydial ophthalmitis 153
Chloramphenicol 171, 424, 425, 456, 581
Chlorhexidine 114, 118
gluconate 462
Chloroquine 599
Chloroxylenol 462
Cholangitis 311
Cholecystitis 98, 243, 434
Cholera 10, 210, 262, 263, 265, 490, 517
confirmation of 263
homeland of 262
toxin 262
vaccine 493, 509, 518, 530
Cholestasis 312
Chorea 243
Chorioamnionitis 150
Ciclopirox olamine 230
Cilastatin 106, 588
Ciprofloxacin 63, 106, 198, 217, 245, 248, 454, 455, 457, 556, 582
Cirrhosis 218, 305
Citrobacter 62, 150
Civil Society Organizations 22
Clarithromycin 34, 132, 135, 163, 268, 582
Clavulanate 65, 106, 199
Clavulanic acid 35, 65, 170, 171, 583
Clindamycin 132, 217, 237, 556, 557, 583
doses of 237
Clinical pulmonary infection score 112
Clofazimine 285, 286
Clostridium 234
botulinum 443
toxins 445
difficile 39, 108, 206, 212
difficile infection 442, 443
diagnosis 443
pathogenesis 443
prognosis 443
treatment 443
difficile toxin assay 209
perfringens 102, 438, 439
tetani 259, 440, 442
Clotrimazole 230, 231, 232, 631
application of 231
Cloxacillin 237, 583
plus cefotaxime 237
Coamoxiclav 198, 583
Coccidioides immitis 397
Coccidioidomycosis 373, 397
Codeine 265
Cold
agglutinin 267
boxes 538
chain 536
Colitis, amebic 412f, 413
Collagen vascular disease 298
Colloids 639
Colony stimulating factors 106
Combination therapy, basis of 275
Common cold 157
epidemiology 157
treatment 158
Complete blood count 94, 216, 335, 454
Congestion
conjunctival 288
vascular 362
Conjunctiva 101, 288
Conjunctivitis 288
painful 547
Constipation 259, 300, 444
Contact infection 431
Continuation therapy 561
Continuous positive airway pressure 331
Convulsions 272
Coombs’ negative hemolytic anemia 145
Coombs’ test 267, 433
Cordocentesis 147
Coronaviruses 158, 310, 525
Corticosteroid 86, 177, 286
therapy 288, 434
use of 186
Corynebacterium
diphtheriae 48f, 129, 159, 249, 250f
ulcerans 249
Cotrimoxazole 131, 141, 163, 171, 218, 450, 456, 584
doses of 134t
Cough 28, 160, 169t, 242, 287, 288, 334, 335
paroxysmal nature of 256
Coxiella burnetii 190, 266
Coxsackievirus 310
types
A 157, 185
B 185
Cranial nerve 399
involvement 302
palsies 182, 267
C-reactive protein 75, 93, 94, 216, 235, 311, 428, 546, 560
Creatinine phosphokinase 311
Crohn's disease 411
Crotamiton 632
Croup syndrome 163
pathophysiology 163
Cryoglobulinemia 308
Cryotherapy 557
Cryptococcal disease 133
Cryptococcosis 398
extrapulmonary 373
Cryptococcus neoformans 54, 398
Cryptosporidiosis 47, 373
Cryptosporidium 105, 206
antigen 409
infections 103, 409
infestation 408
parvum 52, 408
Crystal violet-blood agar 49
Cyclosporin A inhibits 561
Cystic fibrosis 337
Cystitis 196, 267
hemorrhagic 196
Cystourethrogram, micturating 199
Cysts 209, 414
dermal 435
Cytokine 350, 470
production, defective 102
tsunami 350
Cytomegalovirus 88, 103, 133, 136, 137, 158, 168, 206, 305, 309, 371, 524
infection 83, 373
vaccines 532
D
Dapsone 134, 285, 450, 595
Daptomycin 59
Dark-field microscopy 427
Darunavir 375
Deafness 137, 243, 295, 296, 298
Decolonization therapy 60
Deep tendon reflex 302
Deep vein thrombosis 98
Dehydration 208, 208t, 356, 634
hyponatremic 634
physical signs of 634
severe 208, 210, 635
status 263
assessment of 263t
Dendritic cells 350, 472, 473, 474f
Dengue 20, 348, 349, 352, 354, 358, 360, 452
antiviral drugs 363
chimeric vaccine 524f
clinical management 356
diseases 348
facies 353f
fever 81, 88f, 310, 349, 351, 636
hemorrhagic fever 348351, 639
illness 12, 348
course of 354f
infection, primary 96
purpuric rash 353f
severe 352, 354, 358
shock 355, 358, 359, 362
syndrome 310, 348, 352, 639
vaccine 363, 530
virus 305, 310, 349, 350, 355, 364
multiple 348
Dental infections 439
Deoxycholate 126
citrate 49
Deoxyribonucleic acid 52, 126, 429
Dermal sinus 101
Dermatitis 405
Dermatophyte infections 393
Dexamethasone 240
Diabetes 92, 247
mellitus 337, 509, 636
Diaper dermatitis 395
Diarrhea 9f, 28, 205, 208t, 209, 211, 213t, 242, 289, 291, 366, 372, 414, 482, 634
acute 205, 207t, 211, 634
bloody 205
antibiotic associated 442
chronic 405
infective 205
management of 635
mild 210
osmotic 207
persistent 205, 210212
risk of 205
secretory 207
severe 210
small bowel 208
Diarrheal diseases 262, 634
control program 10
Dichlorodiphenyltrichloroethane 451
Didanosine 375, 604
Diethylcarbamazine 626
DiGeorge syndrome 102, 103, 514
Digestive tract 72
Digital thermometers 542, 542f
Digits, gangrene of 420f
Diloxanide furoate 623
Diltiazem 86
Dimercaptosuccinic acid 198, 199
Diphenoxylate 265
Diphtheria 2, 128, 249, 251f, 253, 504
and tetanus 484, 501, 536, 538, 539
toxoids and pertussis vaccine 491
vaccine 504
antitoxin 252
conjunctival 251
control of 253
cutaneous 251, 252
incidence of 14
mild 251
nasal 250
nasopharyngeal 252
pertussis and tetanus 483, 484, 501, 503, 536, 538, 539
signs of 250, 252
symptoms of 250
tonsillar 250, 250f
toxin 249
toxoid 475
Diphtheritic cervical lymphadenopathy, bull-neck appearance of 251f
Diphyllobothrium latum 407
Dipstick test 244
Direct agglutination test 447
Direct fluorescent antibody testing 257
Directly observed treatment short-course 277
Disaccharidase deficiency 414
Disease burden 149, 335, 446
Disk diffusion method 65
District Level Disease Surveillance 20
Donovanosis 553
Doripenem 67
Double disk synergy 65
Doxycycline 268, 424, 425, 434, 435, 557
Drotrecogin alpha 98
Drug 43
allergy 80
resistance, multiple 108
resistant nosocomial infections, risk of 98
sensitivity testing 274
Duck embryo vaccine, purified 464, 511
Dwarf tapeworm 408
Dysarthria 444
Dyselectrolytemia 362, 633
Dyselimination syndrome 200
Dysentery 207
Dyspareunia 554
Dysphagia 158, 442, 444
Dysplasia, thymic 102
Dyspnea 253, 401
Dysrhythmias 441
Dysuria 441, 554
frequency syndrome 195
E
Ear infections 291
Earlobe, gangrene of 420f
Ebola viruses 310, 533
Echinacea purpurea 158
Echinococcosis 408
Echoviruses 185, 289
Econazole 631
Ecthyma 224, 224f
Ectoparasites 553
Eczema formation 221
Edema
periorbital 547
pulmonary 361, 384
Edematous areola 224
Edmonston-Zagreb strain 291
Efavirenz 375, 378, 614
Electrocardiography 251
Electrolytes 183, 638
disturbances, diarrhea-associated 211
Electronic vaccine intelligence network 23
Elek test 251
modified 251
Emergency vaccine retrieval and storage 543
Empiric antibiotic therapy, duration of 126
Empyema 372, 413
necessitans 272
Emtricitabine 375, 378
Encephalitis 6, 180, 182, 248, 267, 294, 297, 314, 325, 520
acute postinfectious 79
glomerulonephritis 321
postinfectious 297
rickettsial 420
sentinel surveillance 21
syndrome, acute 180
Encephalomyelitis, acute disseminated 181
Encephalopathy 182
metabolic 182
Endemic infectious diseases 481
Endocarditis 435
culture-negative 193
diagnosis of 189
infective 131, 188190, 192t
management of 190
staphylococcal 193
streptococcal infective 191
Endocrine disorders 337
Endolimax nana 206
Endoscopic retrograde cholangiopancreatography 404
Endoscopy 412
Endothelial cells 418
Endotracheal tube 111, 113
suctioning 113
Endovascular infection 248
Entamoeba histolytica 206, 212, 219, 410
Enteric fever
diagnosis of 454
treatment of 456
Enterobacter 62, 215
Enterobacteriaceae 68, 109, 135
Enterobiosis 406
Enterobius vermicularis 406
Enterococcal endocarditis 193
Enterovirus 73, 80, 136, 157, 158, 185, 298
Enzyme immunoassay 81, 340, 411
test 244, 455
Enzyme labeled antihuman immunoglobulin 54
Enzyme linked immunosorbent assay 54, 88, 275, 284, 329, 356, 373, 395, 405, 424, 425, 433
antigen capture 54
tests, antibody detecting 54
Eosinopenia 447, 454
Eosinophils 102, 398
Epidemic typhus 421
Epidermophyton floccosum 394
Epiglottitis 164, 164t
Epilepsy 137
Episodic therapy 316
Epistaxis 242, 254
Epstein-Barr virus 78, 82, 88, 104, 158, 267, 305, 309, 368, 559, 561
Equine rabies immunoglobulin 462, 511
Ertapenem 67
Erysipelas 224, 225f
Erythema 120
desensitization of 252b
infectiosum 78, 80, 82, 289, 319, 321
diagnosis of 321
rash of 321
marginatum 78
multiforme 78, 80, 84
nodosum 78, 267, 398
leprosum reactions 286
perianal 208
Erythematous popular lesions 435
Erythrocyte
membranes 266
sedimentation rate 81, 235, 267, 560
Erythromycin 34, 163, 268, 556, 586
Erythropoiesis, dermal 295
Erythrovirus 318
Escherichia coli 33, 62, 66, 66t, 73, 91, 104, 109, 116, 135, 150, 196, 203, 215, 433, 523, 634
vaccines, enterotoxigenic 529
Esophageal candidiasis 373
Essen schedule 464
Ethambutol 135, 276278, 596
Etravirine 375
European Society Medical Oncology 125
Exanthem 294
subitum 80, 289
Exanthematous pustulosis, acute generalized 86
Exotic viruses 310
Extended-spectrum beta-lactamase 51, 62, 63, 66, 69, 70, 198
infections 64t
treatment of 68t
types of 63t
Extracellular fluid 633
Extracorporeal membrane oxygenation 329
Extrafollicular reaction 477
Eye 139, 143, 295, 314
problems 296
F
Fabricius, bursa of 472
Facial palsy 298
Faine's criteria, modified 428
Falciform ligament 215
Famciclovir 315, 316
Familial cold auto-inflammatory syndrome 549
Familial mediterranean fever 546, 546t
epidemiology 546
genetics 546
prognosis 547
treatment 546
Fasciitis, necrotizing 439
Fastvax vaccine 533
Fatigue 304, 334, 369
Fatty liver 378
Febrile neutropenia 105, 125
treatment of 105
Federation of Obstetrics and Gynaecological Societies of India 344
Fetal
hydrops 321
infection 140, 320
rubella-infection 296
Fetus 138, 140, 141
infection of 139, 141
Fever 73, 78, 88, 247, 272, 287, 300, 314, 328, 334, 335, 351, 369, 372, 382, 384, 387
enteric 241, 454
hemorrhagic 183
rickettsial 420, 423
Fibrinogen 560
Filaria 452
Filariasis, lymphatic 20, 452
Filatov-Dukes disease 319
Fine needle aspiration 273
Fish tapeworm 407
Flaccid paralysis, acute 19, 301, 303, 502
Flaviviruses 180
Fleroxacin 457
Flu 332, 334
Fluconazole 135, 203, 397, 557, 619
Flucytosine 397, 619
Fluid 329
amount of 639
and electrolyte imbalances 265
choice of 357, 639
filled bio-safe liquid thermometers 542
inside cells 633
management 209, 210
outside cells 633
overload 361
therapy 633636, 639
Flumazenil 620
Fluorescent
leprosy antibody absorption test 284
polarization immunoassay 434
Fluoroquinolone 35, 68, 217, 245, 425, 456, 457
antibiotics, doses of 237
susceptibility testing 454
Food-borne
botulism 443
disease 148
infections 431
Forchheimer's sign 289, 290
Forchheimer's spots 294
Foscarnet sodium 605
Fosfomycin 68
Fournier gangrene 440
Framycetin sulfate 628, 630
Francisella tularensis 266
Freeze sensitive vaccines 536, 539
Fresh frozen plasma 639
Full blood count 359, 360
Fungal infections 381, 393, 400, 402
diagnosis of 402
invasive 402
opportunistic 372, 400, 401
systemic 393
Fungemia 399
Fungi 48, 167
infections 105
Furazolidone 587, 623
Furuncle over eyelid 223f
Furunculosis 223, 223f
Fusarium 104
Fusidic acid 226
Fusobacterium 234, 438
necrophorum 438
nucleatum 438
G
Gamma aminobutyric acid 440
Gamma benzene hexachloride 221, 627
Ganciclovir 138, 606
Gastric aspirate 273
acid-fast bacilli 146
Gastric lavage 272
Gastroenteritis 247
Gastroesophageal reflux 144
Gastrointestinal
disturbances 300
fluid 639
symptoms 267
tract 101, 242, 267, 288
GAVI's health system strengthening grants 22
GAVI's strategy 22
Genital
blisters 556
herpes 314, 316, 556
ulcer 554
warts 343, 556, 557
Genitourinary
complications 435
manifestations 432
Genotype tests 374
Gentamicin 34, 63, 133, 154, 177, 435, 587
dose of 557
loading dose 557
Geographical information system 452
German measles 83, 294
Ghon focus 270, 271
Gianotti-Crosti syndrome 83, 369
Giardia 206
duodenalis 212
intestinalis 414
lamblia 49f, 206
life cycle 414
Giardiasis 410, 414
prevention of 415
Gingivitis, acute necrotizing ulcerative 372
Gingivostomatitis 315
Glandular fever 368
Glatiramer acetate 534
Glaucoma 296
congenital 295, 296
Global influenza disease burden 333
Glomerulonephritis 85, 308, 435, 450
Gloves and socks syndrome 319, 320
Glucocorticoids 404
Glucose
6-phosphate dehydrogenase deficiency 420
facilitated sodium 264
Gluteus medius 566
Glycogen storage disease 311
Glycosaminoglycans 350
Glycosuria 251
Gonococcal infection, disseminated 78
Graft versus host disease 514
Gram stain 47, 48f, 268
Granular casts 427
Granulocyte transfusions 106
Granulocytopenia 378
Granulomatous disease 107, 430
Gravis colonies 249
Gravis strains 253
Gray-white papules 79
Griseofulvin 620
Growth
failure 372
retardation 414
Guillain-Barré syndrome 85, 213, 267, 302, 308, 324, 337, 370, 444, 509
Guinea worm disease 18
Gum bleeding 354
H
Haemophilus ducreyi 553
Haemophilus influenzae 21, 24, 33, 3436, 42, 49, 73, 77, 91, 103, 104, 116, 150, 161, 162, 165, 167, 170, 172, 174, 234, 236, 290, 433, 439, 475, 505, 515, 516, 521, 539
disease, invasive 6
Hair growth 283
Hand hygiene 39, 110, 114
Hand rubs, alcohol-based 110
Hand washing 564
steps of 565f
Hand, foot and mouth disease 85
Hansen's disease 281, 366
Hantavirus 88
Hartley's blood agar 243
Hartley's media 454
Head louse infestation 222
Headache 242, 297, 314, 334, 335, 369
HEADSSSS screening 553b
Healthcare worker safety devices 570
Hearing loss 296
Heart
defects, congenital 142
disease 267, 294
congenital 296, 337
rheumatic 129, 132
failure 147, 267, 636
congestive 193, 337, 355
rate 91
Heat
and light sensitive vaccines 536
and moisture exchange 114
Hecht giant cell pneumonia 288
Helicobacter pylori 242
Helminths 404
Hemagglutination
inhibition assay 366
test 424
Hemaglutinin, tecombinant trivalent 528
Hematemesis 354
Hematocrit 352, 359, 360
faster, levels of 638
Hematological disorder 545
Hematopoietic
growth factors, role of 127
necrosis, infectious 523
stem cell transplantation 561
Hematuria 427
isolated 267
Hemiparesis 182
Hemiplegia 290
Hemoconcentration 351
Hemoglobinuria 267
Hemolysis, autoimmune 387
Hemolytic uremic syndrome 205, 209, 243, 267, 423
Hemophagocytic lymphohistiocytosis
infection associated 559
types of 559
Hemophagocytic syndrome 368, 420, 559
infection associated 559
Hemorrhage 351
colonic 213
conjunctival 354f
splenic subcapsular 370
Henoch-Schönlein purpura 320, 423
Hepatic dysfunction 91
Hepatitis 243, 294, 295, 310, 355, 378, 539
A 5, 305, 307, 312, 475, 490, 497, 499, 512, 517, 519
influenza 525
prevalence, geographic distribution of 5f
vaccine 492, 495, 507, 517
virus 4, 305, 306f, 308, 309
acute 267, 312
autoimmune 309, 311
influenza 471
monovalent vaccine 24
prevalence, geographic pattern of 4f
surface antigen 305
vaccine 4, 491, 495, 505, 517
virus 4, 88, 305, 306, 306f, 523, 525, 563
bacterial 309
C 136, 306, 307, 312, 377, 523
vaccines 532
virus 88, 305, 306f, 307, 309, 563, 568
chronic 305, 308
D 306, 308, 312
virus 306f, 308, 309
E 305, 307, 312
vaccine 532
virus 305
malarial 311
non-viral 310
vaccines 532
viruses 306
Hepatorenal syndrome 427
Hepatosplenic candidiasis 396, 397
Hepatotoxicity 378
Herpes 143
encephalitis 317
gladiatorum 316
labialis 315
simplex 105, 130, 181, 310
infection 133, 313, 372
viral focal infection 85
virus 88, 126, 137, 143, 158, 180, 310, 313, 314, 316, 317
zoster 85, 87f, 133, 323, 326, 372
maternal 324
Heterophile antibody test 369
Highly active antiretroviral therapy 134, 279, 312, 376
Hip
joint 546
pain, causes of 239
Histoplasma capsulatum 399
Histoplasmosis, extrapulmonary 373
Hodgkin disease 368
Hookworms 407
Hospital waste, management of 41
Host cell 417
invasion of 417
Host immune function 35
Human albumin 639
Human bocaviruses 318
Human bovine
pentavalent live vaccine 341, 507
rotavirus vaccine 508
Human cytomegalovirus 139, 532
infection 137
Human diploid cell vaccine 464, 511
Human herpesvirus 6, 73, 81, 82, 88, 310
Human hookworm vaccine 533
Human hyperimmune globulins, homologous 470
Human immunodeficiency virus 12, 55, 88, 133, 135t, 136, 298, 310, 371374, 471, 484, 515, 523, 525, 551, 563
clinical manifestations of 371
coinfection 450
diagnosis of 373
disease
end-stage 372
progression, monitoring of 373
encephalopathy 373
infection 12, 12t, 19, 104, 270, 281, 288, 325, 372t, 376
global view of 13f
mother to child transmission of 134t
pathogenesis of 371
postexposure prophylaxis 568
syndrome
acute 369
perinatal transmission of 371
transmission 371
prevention of 134
treatment of 377
vaccines 527
Human metapneumovirus 157
Human monocyte-derived macrophages 350
Human monovalent live vaccine 341, 507
Human papillomavirus 343, 471, 499, 533, 557
infection 5, 343, 344
vaccines 346, 493, 494, 509, 517, 518
Human parainfluenza virus 528
Human parvovirus B19 310
Human rabies immunoglobulin 462, 511
Human tetanus immunoglobulin 260
Hutchison teeth 145
Hyaline 427
Hybridization 285
Hydatid disease 408
Hydration 258
Hydrocephalus 178f, 399
Hydronephrosis 200
Hydrops fetalis 319
Hydroxycholoroquine 86
Hydroxyethyl starches 639
Hymenolepis nana 408
Hyperbilirubinemia 137, 218, 312
Hypercytokinemia 561
Hyperglycemia 378, 636
Hyper-IgD periodic fever syndrome 547, 548
Hyperimmunoglobulinemia D 546
Hyperkalemia 639
Hyperlactatemia 59, 384
Hyperlipidemia 378
Hypermagnesemia 444
Hypernatremia 210, 213
Hyperparasitemia 384
Hyperpyrexia 28
Hypersensitivity syndrome, systemic 86
Hypersplenism 387
Hypertension 636
labile 441
Hyperthermia 242
Hyperthyroidism 295
Hypertonic solution 330
Hypoalbuminemia 218, 457
Hypocalcemia 442
Hypoglycemia 183, 213, 251, 384
Hypokalemia 213, 639
Hyponatremia 213, 423, 638
fatal 633
Hypoproteinemia 423
Hypotension 91t, 243, 356
orthostatic 444
Hypothermia 218
Hypotonia 137
Hypotonic hyporesponsive episodes 503
Hypovolemia 356
Hypoxemia 152, 401
Hypoxia 172
I
Icteric form 427
IDL TUBEX test 244, 456
IgM dipstick test 456
Imipenem 67, 69, 106, 217, 588
Imiquimod 557
Immune reconstitution inflammatory syndrome 378
Immunity 387, 418
acquire active 469
active 469
adaptive 472, 472t, 473f
cell mediated 284, 418, 470
cellular 469
flaviviral 182
herd 482
innate 472, 472t, 473f
nonspecific 472
passive 469
specific 472
vaccine induced 475t
Immunization 470
programs 536
schedule 501
Immunodeficiency syndrome, severe combined 103, 409, 513
Immunofluorescent
antibody method 329
assay 81, 424, 425
Immunoglobulin 470, 515
use of 292
Immunoperoxidase assay 424, 425
Immunosuppressive therapy 107
Impetigo 223
contagiosa 224f
In situ hybridization 285
Indian Academy of Pediatrics 254, 292, 296, 325, 344, 568
Indian Association of Leprologists 282
Indian Council of Medical Research 21
Indian Data on Directly Observed Treatment Short-Course Strategy 277
Indian Medical Association 344
Indian Neonatal Rotavirus Live Vaccine 508
Indian tick typhus 421
Indinavir 375
Indirect fluorescent antibody tests 54
Indwelling catheters 123
Infection 90, 117, 207, 323
asymptomatic 399
chronic 534
congenital 136
control
committee 110
measures 71
team 71, 110
disseminated 314, 399
enteric 396
focus of 75
healthcare associated 38, 108
hospital-acquired 108
management of 69, 136
necrotic 223
neonatal 149
nosocomial 38, 92, 97, 108, 135
perinatal 314, 316
pleuropulmonary 439
primary 313, 316
reservoir of 430
systemic 131, 397
tuberculous 226
types of 51, 64, 438
Infectious Diseases Society of America 105, 125
Infectious Diseases Surveillance in India 16
Inflammatory bowel disease 439, 545
Influenza 14f, 105, 130, 158, 332, 471, 475, 490, 513, 519, 539
A virus, types of 334
complications of 335
Disease
burden of 333
Surveillance in India 333
infection, confirmation of 335
pediatric 332
seasonal vaccination 336
sentinel surveillance 21
vaccination 336
vaccine 493, 495, 509, 517
inactivated 336, 509, 509t
live attenuated 336, 488, 499, 509
newer 528
next generation of 528
virus 157159, 332, 333
Inguinal bubo 555
Inguinal lymph nodes, painful enlargement of 555
Inhalation therapy 101
Injection
reaction 483
route 500
waste, disposal of 569
Innate immune system 474
Insulin deficiency 295
Integrase strand transfer inhibitors 375, 377
Integrated disease surveillance project 4, 20, 21
Intensive care unit 62, 92, 169b
Intensive supportive care 330
Intercell intradermal vaccine patch 526f
Interferon gamma radioimmunoassay 275
International Pediatric Sepsis Consensus Conference 90t
Intestinal worms 404
Intra-abdominal infection 68, 215, 439
Intracellular
fluid 633
parasites 417
Intracranial pressure 174, 182
Intracranial tension 243
Intradermal injections 465, 487, 567, 567f
technique 466
Intradermal rabies vaccination 465
Intradermal vaccination 491
Intramuscular injection 301, 566, 566f
Intrauterine fetal death 318, 320
Intravascular coagulation, disseminated 243, 310, 314, 315, 324, 355, 559
Intravenous immunoglobulin 144, 321
Intravenous therapy 264
Intubation, nasal 113
Iodamoeba bütschlii 206
Iridocyclitis 366
Isoniazid 276279, 597
Isospora belli 206
Isosporiasis, chronic 373
Istamines 158
Itching, severe 222
Itraconazole 126, 397, 400, 620
Ivermectin 622, 627
paralyzes 405
J
Janeway lesions 189
Japanese encephalitis 2, 11, 20, 180, 490, 519
vaccine 493, 495, 510, 517, 530
Jarisch-Herxheimer reaction 434
Jaundice 137, 242, 296, 305, 308
obstructive 311
Job syndrome 103, 107
Joint infection 372
pediatric 237t
K
Kala-azar 20, 386, 287, 390, 446, 448, 452
control of 451
elimination of 452
prevention of 451
refractory 448
transmission of 386, 386f, 452
treatment of 450, 452
vaccine 390
vector 386
Kanamycin 34
Kan-kapya disease 421
Kaposi sarcoma 372
Kawasaki disease 80, 84, 289
Keratitis, interstitial 145
Kernig sign 301
Ketoacidosis, diabetic 182
Ketoconazole 135, 230, 231, 232, 621
Kidney 104
disorders 337
Kingella kingae 189, 234236, 238240
Kirby-Bauer method 51
Kissing disease 368
Klebsiella 33, 68, 91, 104, 109, 135, 215
granulomatis 553
pneumoniae 33, 35, 62, 63, 66, 66t, 69, 92, 116, 150, 203
Knee joint 546
Kolar 821564XY strain vaccine 510
Köplik's spots 79, 287289
Kostmann syndrome 102
L
La Crosse virus 180
Lactate dehydrogenase 356
Lactobacillus 212, 265, 443
Lag phase 277
Lambert-Eaton syndrome 444
Lamivudine 134, 374, 375, 377, 378, 609, 614
Lamotrigine 86
Language disorder 420
Large bowel diarrhea 208
Laryngeal diphtheria 250, 252
Laryngeal obstruction 250
Laryngoscopes 39
Lassa viruses 310
Latex agglutination test 424
Legg-Calvé-Perthes disease 239
Legionella pneumophila 53
Leishman-donovan bodies 386, 446
Leishmania 450, 451
amazonensis 451
donovani 386
parasites 451
stage of 53
Lemierre's syndrome 438
Lepromatous leprosy 283
Lepromin test 283, 284
Leprosy 131, 281, 452
clinical varieties of 282
drugs for 285t
elimination strategy 286
indeterminate 282
mid borderline 283
multibacillary 285t
neuritic 283
pediatric 281
surveillance 20
tuberculoid 282
types of 283t
Leptospirosis 80, 311, 427, 533
Society's criteria 428
Leptotrombidium deliense 422
Lethargy 137
Leucocyte adhesion deficiency 102
Leukemia 288, 369, 471
acute 368
lymphocytic 559
Leukocytes, polymorphonuclear 431
Leukocytosis 369, 412
neutrophilic 29
Leukoencephalitis, acute hemorrhagic 181
Leukoencephalopathy, progressive multifocal 373
Leukopenia 335, 354, 447
Levamisole 622
Levofloxacin 268, 269
Ligase chain reaction 67
Lincosamides 34
Lineal gingival erythema 372
Linezolid 3335, 59, 177, 237, 588
Lipodystrophy 378
Lipopolysaccharide 433
antigen 244
Liposomal amphotericin 448
Liposomal vaccines, several 525
Liposome 525
Listeria 33, 104, 148
diagnosis 148
monocytogenes 73, 91
prevention 148
treatment 148
Liver 104, 182, 387
abscess, amebic 411
biopsy 310
cell failure, acute 429
disease 207, 309, 377
disorders 337
dysfunction 310
failure, acute 310
function tests 183, 412, 560
injury, drug induced 311
Loeffler's syndrome 405
Loperamide 265
Lopinavir 375
Louse infestation 222
Low ejection fraction 356
Low-birth-weight 136, 137, 142, 152
Lower respiratory tract infection 157
Lumbar puncture 94, 96, 175, 182
Lumefantrine 599
Lumens, number of 119
Lung
biopsy, transbronchial 275
disease, chronic 337
Lupus vulgaris 226, 227f
Lutzomyia 386
Lyme disease 183, 239
Lymph node 250, 394
mesenteric 243
regional 225
tuberculosis 372
Lymphadenopathy 294
persistent generalized 372
Lymphangitis 225f
over leg 226f
Lymphocryptovirus 82
Lymphocytic choriomeningitis virus 298
Lymphocytosis 447
atypical 354
Lymphohistiocytosis, hemophagocytic 309, 559, 560b
Lymphoid interstitial pneumonitis 368, 372
Lymphopenia 335
M
MacConkey agar 49, 243, 454
Macrolides 33, 34, 171, 245
Macrophages 431
Maculae ceruleae 223
Maculopapular rashes 78, 353f, 369
Major histocompatibility complex 523
Malabsorption syndrome 414
Malaise 242, 335, 369, 482
Malaria 10, 136, 247, 311, 381, 383f, 452, 526
congenital 384
prophylaxis 130
severe 384b
surveillance 20
transmission 131t
drugs for 131t
types of 131, 131t
vaccine against 523, 526
Malassezia furfur 394, 400
Malnutrition 103, 213, 288
Mantoux test 146, 275, 398
Marburg virus disease 310
Marshall's syndrome 548
Maximal sterile barrier precaution 118
Measles 2, 3, 79, 80, 87f, 100, 287290, 297, 319, 475
complications of 79
containing vaccine 292
face 288f
mumps, pertussis, diphtheria 516
mumps, rubella 181, 293, 325
vaccine 291, 492, 495, 517
varicella 291, 499
prevention of 291
rubella 27, 293
and tetanus 470
and varicella vaccine 298
initiative plan 292
vaccine 291
severe 206
vaccine 291, 504
virus 88, 267, 309, 525
isolation of 289
Mebendazole 404, 406, 623
Mediterranean fever 546
Mefloquine 600
Membranoproliferative glomerulonephritis nephrotic syndrome 267
Memory B-cell 477, 478
Memory T cells 371
Meningitis 85, 178f, 248, 321, 373, 396, 398, 399
acute bacterial 174t
aseptic 267, 297, 301
basilar 398
causes of 73t
cryptococcal 399
meningococcal 6
neonatal 152
nosocomial 68
recurrent aseptic 314
tubercular 6, 183, 270, 272, 278
Meningococcal disease 471
Meningococcal polysaccharide vaccine 499
conjugated 510
Meningococcemia 86, 87f, 289
rash of 290
Meningoencephalitic syndrome 183
Meningoencephalitis 85, 267, 295298, 429
Mental retardation 296
Meropenem 6769, 106, 177, 217, 589
Metabolic acidosis, hyperkalemic 197
Metabolic disorders 337
Metallo-beta-lactamases 109
Methemoglobinemia 198, 450
Methicillin-resistant Staphylococcus aureus 57, 69, 97, 108, 116
Methotrexate 561
Metromenorrhagia 354
Metronidazole 217, 415, 556, 557, 624
Mevalonate kinase 547
deficiency 547
Miconazole 230232, 631
Microglial nodules 181
Microphthalmia 295
Microscopic agglutination test 311
Microsporum canis 393
Midazolam 260
Miliary tuberculosis 270, 272
Milk, pasteurization of 435
Miltefosine 390, 449
Minimum inhibitory concentration 44, 66
method 65
strip 66f
Minocycline 285, 589
Mitochondrial disorders 337
Modern tissue culture vaccines 511
Molecular amplification methods 55
application of 55
Molecular techniques 190
Molecular tests 96
Mollaret's meningitis 314
Molluscum contagiosum 46, 83, 228, 229f, 372
treatment 228
Monobactams 34, 63
Monocytes 431, 476
Monocytosis 447
Mononucleosis, infectious 251, 289, 368, 369
Monotherapy, empirical 97
Mop-up immunization 303, 502
Moraxella catarrhalis 161, 162
Morbilliform eruption 78
Morbilliform rash 287
Morphological index 281
Motor retardation 295
Mouse brain derived inactivated vaccine 510
Mouth disease 85, 143
Moxifloxacin 217
Muckle-Wells syndrome 549
Mucous membranes 101
Mulberry molars 145
Multidrug resistant 458
gram-negative bacteria 62
organism 198, 457
Plasmodium falciparum 56
salmonella 244
strains 59
tuberculosis 276
typhoid fever 241, 456
Multidrug therapy 285
Multiple organ dysfunction syndrome 90
Mumps 2, 297, 475
diagnosis of 298
incubation period of 297
infection 3
treatment of 298
vaccine 298, 299
virus 83, 297
Mupirocin 60, 226, 630
Murine typhus 421
Murmur, cardiac 432
Muscle 304
weakness 304
Myalgia 242, 267, 314, 369
Mycobacterial growth indicator tubes 274
Mycobacterium
avium complex 135
infections 135, 135t
avium-intracellulare 234
bovis 12, 270
fortuitum 234
gordonae 234
infection 47
isolates, rapid identification of 274
leprae 281
marinum 234
pneumoniae 181, 268
tuberculosis 104, 130, 167, 234, 238, 434, 476
bacilli 270
complex 270
Mycoplasma 84, 86, 170, 266, 269
extrapulmonary manifestations of 267b
genitalium 266
genome 183
hominis 150, 266
infection 78, 266, 268t
drugs for 268t
pulmonary complications of 267b
pneumoneae 42, 167, 183, 266, 268, 401
infection 266
Mycosis, disseminated endemic 373
Mydriasis 444
Myelitis, transverse 85, 243, 267, 298, 302, 324
Myelodysplastic syndrome 127
Myeloperoxidase deficiency 103
Myelosuppression 59
Myocarditis 85, 147, 253, 267, 290, 295, 308, 319, 321, 420, 429
Myoglobinuria 260
Myopathy 378
N
Nail infection, fungal 372
Nalidixic acid 131, 243, 455457
Napoleon's retreat 416
Nasogastric tube 217
National AIDS Control Organization 104, 134, 376
National Centre for Disease Control 460
National Childhood and Antenatal Immunization Programme 20
National Diarrhoeal Disease Control Programme 8
National Immunization Program 3
National Institute of Cholera and Enteric Diseases 23
National Institute of Virology 21
National Malaria Control Programme 20
National Nosocomial Infections Surveillance System 108
National Polio Surveillance Project 19
National Technical Advisory Group on Immunization 518
National Vector Borne Disease Control Programme 20, 186, 389
Natural killer cells 470
Nausea 300, 305, 369
Necator americanus 407
Neck glands, scrofula of 227f
Needle insertion, subcutaneous 487f
Needlestick injuries 567
determinants of 568
immediate management of 568
prevention of 40
Neisseria 52
gonorrhoeae 46, 150, 159, 236, 238240, 553555
infection 239
meningitidis 6, 34, 54, 73, 103, 129, 150, 174, 176, 177, 523
Nelfinavir 375
Nematodes 404
Neomycin sulfate 629
Neonatal herpes 317
simplex virus infection 315
Neonatal intensive care units 108
Neonatal pneumonia, primary pathogens of 152
Neonatal sepsis, treatment of 154t
Nephritic syndrome 145, 324
Nephritis, acute interstitial 267
Nephronia, acute lobar 198, 203
Nephrotic syndrome 129, 170, 215, 216, 218, 220, 321, 324, 427
Nerve
conduction velocity 302
tissue vaccine 467
Netilmicin 589
Neuritis
retrobulbar 290
traumatic 302
Neurogenic bladder 200
Neuropathy, peripheral 267, 378
Neutropenia 335
cyclic 545
mild 125
moderate 125
severe 125
Neutrophil 102, 428, 476
count 138
Neutrophilia 547
Nevirapine 86, 134, 374, 375, 378, 379, 609, 615
Niclosamide 627
Nipah virus 180, 181
Nitazoxanide 415, 624, 628
Nitric oxide, exogenous 327
Nitrofurantoin 68, 131, 590
Nitroimidazole 413
No touch technique 120
Nodule 78
Nonantimicrobial prevention strategies 44
Nonbacterial infections 31
Nonessential catheters, active removal of 120
Non-Hodgkin's lymphoma 373, 559
Nonintestinal infection 208
Non-leishmanial tests 447
Nonlive vaccines 472, 474, 476
Non-nucleoside reverse transcriptase inhibitors 374, 375, 378
Nonpolio Enteroviruses 157
Nonsteroidal anti-inflammatory drugs 311, 321, 366
Non-tuberculous mycobacteria infection, disseminated 373
Nontyphoidal salmonella
infections 246, 247
organisms 248
Norfloxacin 218, 457
Norwalk virus 206
Nucleic acid 536
amplification tests 55, 321
use of 55
Nucleoside reverse transcriptase inhibitors 374, 378
Nutrition, parenteral 120
Nutritional deficiencies 387
Nystatin 557, 621
O
Obstructive pulmonary disease, chronic 337
Obturator sign 239
Ocular infection 316
Ofloxacin 245, 285, 457, 590
sensitivity 454, 455
Oligoarthritis 546
Omenn syndrome 102
Omphalitis 153
Onychomycosis 394, 395
Oophoritis 297, 298
Ophthalmia
neonatorum 153
prevention of 153
Opisthotonus 260, 441
waves of 441
Optic neuritis 243
Optimal immunization schedules, determinants of 495
Oral acyclovir 85
Oral amoxicillin 129
Oral antibiotic 237
doses of 237, 237t
Oral candidiasis 395, 396
persistent 372
Oral care 127
Oral cefixime 457
Oral cephalosporins 171
Oral cholera 520
Oral fluconazole 394
Oral fluid requirements 264t
Oral fluoroquinolone 248
prophylaxis 126
Oral hairy leukoplakia 368, 372
Oral ingestion 207
Oral ivermectin 222
Oral polio vaccine 471, 483, 484, 486, 499, 501, 502
live attenuated 302
trivalent 19
Oral poliomyelitis vaccine 536, 538
Oral rehydration
salts 634
solution 10, 32, 264, 357
therapy 210, 211, 634
Oral steroids, use of 548
Oral typhoid vaccine 471, 488
Oral ulcerations, recurrent 372
Oral zinc supplementation 265
Orange peel 466
Orchiepididymitis 435
Orchitis 297299
Organ dysfunction 94
criteria 91t
signs of 93
Organ impairment 355, 362
Organ transplants 104
Orientia tsutsugamushi 311, 421, 422
Ornidazole 413
Orolabial infections 313
Orthotic devices 302
Oseltamivir 611
Osler's nodes 189
Osteomyelitis 233236, 238, 238t, 248, 434
acute 233
hematogenous 233, 234
causes of 240
chronic 236, 238
recurrent multifocal 234
classification 233
contiguous focus 235
epidemiology 233
hematogenous 233
microbiology 233
multifocal 236
pathogenesis 233
pathology 233
treatment of 236
Osteoporosis 378
Otitis media 162, 372, 439
acute 75, 161, 162, 163fc, 545
chronic 162
recurrent 162
Otorrhea 372
Overhydration 264
Oxiconazole 230, 231
Oxoplasmosis 625
Oxybutynin 200
Oxygen 329
supplementation 362
Oxymetazoline 160
Oxytetracycline 591
P
Pachygyria 138
Packed red blood cells 639
Pain
abdominal 208, 234, 242, 300, 366
frequency of 365f
hypochondrial 305
lower abdominal 554, 555
testicular 547
Palatal paralysis 250
Palivizumab 331, 470
Pallor 319
Palmoplantar pustulosis 234, 236
Palpable purpura 419f
Pancreas 182
Pancreatitis 243, 267, 298, 308, 378
Pancytopenia, features of 387
Pandemic virus 332
Panencephalitis, subacute sclerosing 288, 290
Papanicolaou test 344, 346
Papillomatosis, recurrent respiratory 344
Papular acrodermatitis 83, 369
Papular purpuric gloves and socks syndrome 320
Papule 78
Para-amino-salicyclic-acid 597
Paracetamol 311
Parainfluenza 161
virus 83, 157, 158
vaccines 528
Paralytic poliomyelitis, vaccine associated 303
Paralytic syndrome 438
Paramyxoviruses 288
Parasitemia 53, 91, 183
Parasites 206, 553
Parasitic bowel diseases, prevention of 409
Parasitic infections 105, 381
Paratyphoid vaccines 530
Parenchyma of brain, inflammation of 180
Parenteral antibiotic therapy, empirical 237t
Paromomycin 389, 390, 449
Paronychia 395
Parotid glands 297
Parotitis 297, 439
recurrent 298
Parvovirus 80, 318
B19 82, 83, 88, 289, 310, 318
infection 318, 319t
infection 147, 318
congenital 147, 147b
Patent ductus arteriosus 142, 295
Paul-Bunnell antibodies 369
Paul-Bunnell-Davidson test 369
Peau d'orange 466
Pediatric
infectious diseases 28
intensive care units 108
sepsis, management of 98
Pediculosis 222
capitis 222, 222f
corporis 222, 222f, 223f
pubis 223, 223f, 557
Pelvic
infection 236
inflammatory disease 551, 557
osteomyelitis 234, 236
Penicillin 33, 62, 129, 591
allergy 160
binding proteins 35
G 177, 576, 591
hydrolyzing 63, 109
V 160, 591
Pentamidine 134, 450
Pentavalent antimony drugs 448
Perfloxacin 457
Pericardial fluid 427
Pericarditis 248, 267, 278, 295, 413, 546
amebic 411, 414
Periodic acid-Schiff 311
reagent 398
Periodic fever 545, 546, 548
etiology of 545t
syndrome 545, 546, 546t, 549
Periodontitis 372
Peritoneal fluid 243
Peritonitis 216, 219, 413
acute secondary 215, 219
amebic 411
primary 215, 218
secondary 218
Permethrin 221, 223, 557, 628
Personal protective equipment, use of 39
Pertussis 2, 128, 168, 256, 257, 470
diagnosis of 257
epidemiology of 518
infection 2
risk of 488
outbreak 488
vaccination 518
vaccines, newer 529
Petechiae 78, 137
Petechial rash 353f
Peyer's patches 270, 339
Pfeiffer's disease 368
Phagocyte
mononuclear 102
polymorphonuclear 102
system 102
disorders of 102
Phagocytic function 514
Pharyngeal diphtheria 250, 252
Pharyngeal swab 555
Pharyngitis 158, 548
acute 160fc
bacterial 160, 160t
complications 159
diagnosis 159
etiology 158
management 160
nonsuppurative complications 160
serology 159
severe 370
streptococcal 251, 369
suppurative complications 159
Pharyngotonsillitis, recurrent 438
Phenazopyridine hydrochloride 198
Phenol 228
Phenotypic confirmatory
methods 65
test 65f
Phenoxymethylpenicillin 591
Phenylbutazone thiouracil 298
Phlebotomus 386
argentipes 386, 452
Piperacillin 106, 135, 199, 217, 592
Piperazine citrate 404
Pityriasis rosea 228, 229f
natural history 230
treatment 230
Pityriasis versicolor 232, 232f
treatment 232
Pityrosporum orbiculare 78, 394
Plague 131
Plasma 633
Cells
long-lasting 478
primary 477
secreting 477
Plasmodium
falciparum 10, 183, 311, 381, 384, 526
parasites 383f
species, life cycle of 381, 382f
vivax
infection 311, 526
malaria 384
Platelets 470
transfusion 361
Pleuritis, unilateral 546
Pluckability of hairs 231
Plus doxycycline 557
Pneumococcal conjugate 475
vaccine 8, 491, 508
Pneumococcal disease, invasive 8
Pneumococcal polysaccharide vaccine 492, 508
Pneumococcal surface protein
A 529
C 529
Pneumococcal vaccines, newer 529
Pneumocystis carinii 18, 92, 98
pneumonia prophylaxis
drugs for 134t
indications of 133
Pneumocystis infection 401
Pneumocystis jirovecii 103105, 167, 371
infection 401
pneumonia 275
pneumonitis 103
Pneumolysin 529
Pneumonia 7, 112, 167, 168, 169, 243, 248, 250, 291, 325, 327, 399, 525
apical lobe 168
atypical 167, 266
community-acquired 167, 172, 266
etiology of 172
healthcare associated 110, 112, 116
hospital-acquired 110, 116
incidence of 152
neonatal 152
nonresolving 275
nonsevere 171
nosocomial 116
pneumocystis 372, 401
prevention of 172
severe 169, 171
severity of 169t
treatment of 171
ventilator associated 108, 110, 111, 112t, 115, 116
Pneumonitis, necrotizing 267
Podofilox 557
Podophyllin resin 557
Polio 2, 452, 470, 490
encephalitis 301
eradication 303
sabin 475
salk 475
survivors 304
vaccination, injectable 499
vaccines 502
bivalent 502
inactivated 24, 253, 302, 502, 539
monovalent 502
types of 502
Poliomyelitis 3, 300, 302, 302t
abortive 300
nonparalytic 301
paralytic 301, 301b
Poliovirus 3, 19, 300, 303
circulating vaccine derived 303
strain 532
types 532
vaccines 491
Pollakiuria 196
Polyacrylamide gel electrophoresis 339
Polyarteritis
nodosa 308, 320
papular acrodermatitis 308
Polyarthritis 267
incidence of 294
Polyarthropathy syndrome 319
Polyclonal B-cell activation 82
Polymerase chain reaction 52, 55, 67, 81, 88, 138, 140, 190, 244, 257, 263, 268, 274, 295, 308, 315, 325, 329, 366, 373, 402, 411, 425, 434, 456
reverse transcriptase 289, 334
testing 257
Polymicrobial infections 37
Polymicrogyria 138
Polymyxin 68, 98
Polyradiculitis 298
Polysaccharide
capsules 499
conjugate vaccine 506
vaccine 246, 471
Pork tapeworm 408
Porphyromonas 438
Postexposure prophylaxis 130, 134, 292, 326, 460, 461, 466, 467, 511, 567, 568, 568fc
Postnatal infection 294
Post-polio syndrome 304
Post-transplant lymphoproliferative disease 368
Potassium
antimony tartrate 286
hydroxide 393
permanganate 629
Povidone iodine 462, 629
Praziquantel 407, 408
Prednisolone 561
Pre-existing antibodies, role of 351
Pre-exposure prophylaxis 511
Prevotella 438
Primaquine 601
Pristinamycin 86
Probiotics 212
Procalcitonin 94, 95
Proctitis 557
Proguanil 601
Prophylactic antifungals, role of 127
Prophylactic therapy 36
Prosector's wart 227
Prosthetic
devices 192
valve 132
endocarditis 193
Protease inhibitors 375, 378
Protein 302, 536
energy malnutrition 639
nonstructural 340, 349
Proteinuria 202, 216, 427
transient massive 267
Proteus 33, 195
mirabilis 33
vulgaris antigen 424
Prothrombin time, activated partial 560
Protozoa 48, 404
Protozoal diseases 423
Protozoal infections 381
Pruritus 325
Pseudallescheria boydii 104
Pseudomembranous colitis 442, 443
Pseudomonas 34, 109, 135, 195
aeruginosa 36, 62, 68, 102, 104, 116, 177, 198, 203, 219, 246
exotoxin 506, 533
infection 36
Psychiatric sequelae 186
Psychosis 243, 378
Ptosis 444
Pubertal estrogens 553
Pubic hair 223f
Pulmonary disease
acute 399
chronic 397
Pulse
immunization 502
peripheral 360
pressure 360
narrowing 358
Pure red cell aplasia 319
Purpura 78, 296, 435
fulminans 85
Pyelitis 434
Pyelonephritis 195
acute 195
focal 203
severe 198
Pyogenic arthritis 238
causes of 240
complications of 240
epidemiology 238
management of 240
pathogenesis 238
Pyogenic infection, superficial 223
Pyomyositis 372
Pyrantel pamoate 404
Pyrazinamide 276278, 598
Pyrethroids 452
Pyrexia unknown origin 243
Pyridoxine, indications of 278
Pyrimethamine 141, 601, 602, 625
Pyuria 195
Q
Q fever 266, 420
Quadrivalent vaccines 336
Quinine 602
Quinolones 35, 36, 63, 68, 86, 109, 455
R
Rabies 181, 470, 475, 490, 517, 519
exposure, categories of 511t
immunoglobulin 462, 511
administration of 463
dose of 462
infiltration of 463f
local infiltration of 462
monoclonal antibody 464, 511
problem of 460
prophylaxis 460
vaccine 494, 511, 518
virus 525
Radionuclide bone 235
Raised intracranial pressure, control of 185
Raltegravir 376
Randomized controlled trials 115
Rapid antigen detection tests 159
Rapid diagnostic test 388
Rapid malarial antigen tests 94
Rapid streptococcal antigen test 159
Rash 80t, 88, 147, 378
hemorrhagic 86
necrotic 419f
petechial 419f
polymorphous 84
vesicular 84, 267
Rational antibiotic therapy 29
Rational drug
selection 28
therapy 28, 32
Rational injection therapy 565
Rectal swab 555
Rectum, uncomplicated gonococcal infections of 556
Recurrent infections, management of 316
Red blood cell 88, 320, 470
Red-flag signs 209
Reflux nephropathy 202
Regurgitation 253
Rehabilitation 186
prevention 186
prognosis 186
Rehydration 210
salts solution 264
Renal disease 377
Renal dysfunction 91
Renal failure 260, 429, 636
acute 427
chronic 267
Renal function tests 183
Renal infection 396, 397
Respiratory
distress syndrome, acute 267, 334, 361, 429, 635
dysfunction 91
failure 144, 267
infection 13, 28, 157
isolation 258
rate 91, 91t
syncytial virus 83, 157, 327, 528
infection 327, 329
treatment 127
vaccines 528
syndrome 420
tract 101, 288
infection 327, 372, 635
obstruction of 253
transmission 318
viruses 371
Restriction fragment length polymorphism 52, 67
Reticuloendothelial system 431, 446
Retinitis 366, 373
Retinopathy, pigmentary 296
Revised National Tuberculosis Program 12, 273
Reye's syndrome 182, 324, 503
Rhabdomyolysis 260
Rheumatologic disease 239
Rheumatologic disorders 247
Rhinitis medicamentosa 158
Rhinorrhea 157, 160, 335
Rhinosinusitis 160
Rhinovirus 157, 158, 161
Rhipicephalus 421
sanguineus 421
Ribavirin 366
Ribonucleic acid 349
ribosomal 52
Rickets infection, diagnosis of 424
Rickettsia 417, 418, 423
isolation of 423
movement of 418f
pathophysiology of 418
prowazekii 418
typhi 418
Rickettsial diseases 416, 420, 421, 423, 424
classification of 416, 417t
Rickettsial illness, diagnosis of 423
Rickettsial infections 183, 290, 369, 416, 418, 422, 422b, 423, 425fc
classification 416
epidemiology of 416
etiology 417
method of transmission 417
microbiology 417
pathophysiology 417
Rickettsial microorganisms 418
Rickettsial organisms 417
Rickettsial pathogenesis 417
Rickettsialpox 422
diagnosis 422
Rickettsioses, laboratory diagnosis of 423
Rifabutin 135
Rifampicin 177, 276279, 285, 377, 425, 450, 592, 598
Rifampin 129, 435
Ringer's lactate 264, 357, 639
Ritonavir 375
Robertson's cooked meat broth 49
Rochester criteria 74t
Rocky mountain spotted fever 80, 84, 416, 421
Romanowsky stains 47
Roseola 78, 80
erythema infectiosum 319
infantum 78, 82, 289
Rose-pink macules 83
Rotadiarrheas 634
Rotavirus 83, 100, 206, 207, 339, 340, 471, 475, 490, 499
disease 339
infections 340
natural 340
replication 339
sentinel surveillance 21
vaccine 340, 342, 492, 507, 513
development 342
interchangeability of 342
Roth spots 189
Roundworms 404
Routine cervical cancer screening 346
Roxithromycin 450, 592
Rubella 2, 81, 83, 136, 141, 289, 294, 297, 319, 475
infection 3, 83, 294, 295
vaccination 142
virus 88, 294, 297
classical congenital 142
management of 296
syndrome, congenital 3, 24, 83, 141, 142, 143b, 292, 294, 295, 295t, 296
Ruiz-Castañeda system 432
S
Sabin-inactivated poliovirus 532
development of 532
Sabouraud's agar 49
Saccharomyces boulardii 212, 443
Sacroiliitis 434
Saddle back fever curve 365
Saddle nose 145
Safe injection practices, specifics of 564
Salivary duct calculi 298
Salivary glands 297
Salmeterol multicenter asthma research trial 109
Salmonella 100, 103, 104, 207, 208, 212, 310, 454
bacilli 241
bacteremia 248
infection 212, 241, 244, 247
organisms 247, 248
paratyphi 91, 454
infection 456
shigella agar 248
typhi 91, 241, 310, 471, 454
typhimurium infections 51
Salt and pepper appearance 295
Saponins 525
Saquinavir 375
Sarcoidosis 275
Sarcoptes scabiei 221
Scabies 557
burrows penis 221f
lesions 221f
over soles 221f
treatment of 221
Scalp hairs, infection of 231
Scarlet fever 78, 289, 319, 369
staphylococcal 81
streptococcal 81
Schick test 251
Schistosoma haematobium 533
Schistosoma mansoni 533
Schistosomiasis 533
Scrofuloderma 228f
scars 228f
Scrub typhus 311, 417, 421, 422
Seasonal flu, vaccinated against 337
Seasonal human influenza 333
Secnidazole 413
Seizures 137, 242
Selective decontamination of digestive tract 115
Sensation 283, 302
Sensitivity test 252
Sentinel surveillance 19
Sepsis 90, 90t
bacterial 310
diagnosis of 96, 151
early-onset 149
late-onset 149
neonatal 149, 151
pathogenesis of 93fc
pathophysiology of 92
pediatric 98, 99, 99fc, 100
prevalence 99
severe 90, 98
Septic arthritis 238, 238t, 240, 251
bacterial 238
Septicemia
diagnosis of 50
gram-negative 34
meningococcal 86
mimicking 73
Serological tests 244, 308, 455
Serology 53, 138, 301
Serratia 103
marcescens 116
Serum glutamic
oxaloacetic transaminase 243, 356
pyruvic transaminase 243, 356
Severe acute respiratory syndrome 306, 310
Sexually transmitted diseases 525, 550, 551, 556
Sexually transmitted infections 551, 551b, 552, 552b, 553, 555, 558
complications of 557
etiology of 552
prevalence of 550
prevention of 557
Sharp waste minimization 569
Shigella 205208, 213
flexneri 52
vaccines 529
Shock 218, 348, 356
compensated 358, 359fc
decompensated 360fc
hypotensive 359
septic 90, 94t, 98, 639
severe 361
treatment of 637
Shwachman-Diamond syndrome 102
Sickle cell
anemia 107, 234
disease 206, 212, 319, 337
Sickle erythrocytes 383
Silver nitrate 228
Simple drug reaction 82
Sinopulmonary infections 545
Sinus aspiration 161
Sinusitis 372
acute 160
chronic 439
Sitamaquine 449
Skin 101, 143, 221, 282, 314, 439
care 127
disease 267, 325, 397
fungal infections of 393
infection 397
lesion 394
congenital 395
neck 251f
manifestations 432
preparation 118
sensitivity test 463
snip cultures 243
swab 251
testing 447
Small particle aerosol generator 330
Sodium stibogluconate 448, 625
Soft tissue infections 221, 439
Solid organ transplant 121, 514
Sore throat 300, 334, 335
Speech disturbance 182
Spherocytosis, hereditary 319
Spinal dysraphism 200
Spinal polio 301
Spiramycin 140, 593
Spirochete denticola 158
Splenectomy 450
Spondylitis 434
Sporothrix schenckii 400
Sporotrichoid infection 400
Sporotrichosis 400
Spotted fever 417, 423
disease 416
group 417
rickettsiae 418
SSHADDESS tool 554b
St. Louis encephalitis virus 180
Standard disk diffusion method 65
Staphylococcal scalded skin syndrome 81, 86, 87
Staphylococcus aureus 34, 36, 42, 51, 58, 59, 73, 87, 89, 91, 97, 102104, 150, 165, 170, 203, 215, 219, 223, 233, 236, 238, 240, 298, 323
bacteremia 57
disease 533
vancomycin-intermediate 35
Staphylococcus epidermidis 36, 215
Stavudine 375
Sterile technique 500
Steroids
indications of 278
role of 186
therapy 325
Stevens-Johnson syndrome 81, 86, 88f, 267, 432, 435
Stomatitis, aphthous 548
Streptococcal antibody testing 159
Streptococcal vaccine 533
Streptococcus agalactiae 177, 234, 236, 238
Streptococcus faecium 265
Streptococcus pneumoniae 34, 53, 73, 77, 91, 100, 103, 104, 116, 129, 150, 152, 161, 162, 165, 167, 170, 174, 175, 177, 217, 236, 238, 240, 475, 508
disease 174
drug resistant 162
strains of 51
Streptococcus pyogenes 51, 97, 150, 234, 236, 238, 240, 289, 290, 323, 369
Streptomyces nodosus 448
Streptomycin 34, 276, 434, 435, 593
Strongyloides stercoralis 52, 206, 405
Strongyloidosis 405
Subcutaneous injection 487, 567, 567f
Sudden infant death syndrome 503
Sulbactam 35, 217
Sulfadiazine 594, 630
Sulfadoxine 141, 602
Sulfamethoxazole 134, 248
Sulfonamide 33, 86
treatment 420
Swabs, nasopharyngeal 257
Swelling 120
inguinal 554
scrotal 554, 555
Swine flu 13
virus 333
Swollen gland 297
Sycosis barbae 226, 226f
etiology 226
management 226
Syndrome of inappropriate
antidiuretic hormone 183, 636
diuretic syndrome 329
Syphilis 523
congenital 144, 145b, 251
early congenital 145
late congenital 145
primary 556
Systemic inflammatory response syndrome 90
Systemic lupus erythematosus 83, 298, 320
T
Tachycardia 91t, 243, 253, 319, 441
Tachypnea 91t, 328
Taenia
saginata 408
solium 408
Tanner stages 377
Tapeworms 404
Tazobactam 35, 106, 135, 199, 217, 592
T-cell 472
activation defects 102
defects 102, 103
dependent antigens, immune responses of 477
immune pathology 350
independent antigens
immune responses of 477
responses 474
receptor, defective 102
Technical advisory committee 351
Teicoplanin 106, 594
Temocillin 68
Temoniera 63
Temperature monitoring devices, types of 541
Tenckhoff catheter 218
Tenofovir 374, 375, 378
Terbinafine 86, 230, 232, 621
Tetanus 3, 259, 261, 440, 470, 484, 504
clinical manifestations 441
diagnosis of 442
diphtheria 130
acellular pertussis 258
pertussis vaccine 256
toxoids 491, 494, 517
vaccine 504
epidemiology of 441
immunoglobulin 442
localized 259, 260
neonatal 2, 153, 259
neonatorum 442
pathogenesis of 440
toxoid 253, 475, 484, 503, 504, 506, 536, 538, 539
doses 260, 504
injection 462
treatment 442
Tetracycline 33, 63, 268, 424, 425, 594
Tetravalent yellow fever, construction of 524f
Thalassemia 319
Thalidomide 286
Therapeutic cancer, types of 534
Therapeutic vaccines 527, 533
Thermometer placement 542
Three-dimensional test 65
Throat swab culture 159
Thrombocytopenia 85, 145, 147, 294, 351, 423, 447
Thrombocytosis 547
Thromboplastin time, activated partial 243
Thyroid deficiency 295
Thyroiditis, suppurative 439
Tigecycline 68, 98
Tinea
capitis 231, 231f, 393
corporis 230, 230f, 393, 394
cruris 230, 230f, 394
faciei 230f
manuum 230, 231f
pedis 230, 231f, 394
unguium 394
versicolor 394
Tinidazole 415, 626
Tipranavir 375
Tissue anoxia 382
T-lymphocyte 350, 514
Tobramycin 34, 63, 594
Tolnaftate 632
Tonsillectomy 301
Tonsillitis 372
Tonsillopharyngitis 75, 158
Tourniquet test 351
Toxemia 91
Toxic epidermal necrolysis 86
Toxic megacolon 213, 443
Toxic shock syndrome 81, 87, 144, 423, 501
Toxicity, signs of 75
Toxoid 477, 536
Toxoplasma 139
gondii 135, 140, 368
serology 140t
infection, primary 139
Toxoplasmosis 135, 136, 139
Toxoplasmosis, congenital 141, 141b
epidemiology 139
etiopathogenesis 139
rubella, cytomegalovirus, and herpis (TORCH) 137
Tracheitis, bacterial 165
Transcellular fluid 633
Transthoracic echo 190
Trauma 239
Traveler's diarrhea 207
Treponema pallidum 553
Trichinella spiralis 406
Trichloroacetic acid 228, 557
Trichomonas vaginalis 553, 554
Trichomoniasis 557
Trichophyton
mentagrophytes 393
rubrum 394
tonsurans 393
Trichuriasis 405
Trichuris trichiura 206, 405
Trimethoprim 134, 248
sulfamethoxazole 63, 248, 401, 435, 457
doses of 237
Tropheryma whippelei 55
Tube agglutination 53
Tubercle bacilli 270
Tuberculosis 11, 20, 31, 136, 146, 147b, 270, 310, 377, 411, 475, 476, 523, 525, 526
chemoprophylaxis 130
congenital 146
cutaneous 227
etiopathogenesis 146
extrapulmonary 270, 271, 372
fibrocavitary 271
forms of 271
hepatitis 310
immunodiagnosis of 275
infection, latent 270
investigation of neonate 146
lymphadenitis 273fc
mortality of 11
pediatric pulmonary 273fc
prognosis 146
pulmonary 270, 372
skeletal 234
symptomatic baby 146
therapeutic response 146
treatment 146
regimens 278
vaccines 527, 527t, 528
newer 527
postexposure 527
pre-exposure 527
verrucosa cutis 227, 228f
treatment 227
Tumor necrosis factor 547, 560
receptor associated periodic syndrome 546
Tympanostomy tube insertion 163
Typhidot test 244, 455
Typhlitis 218, 439
Typhoid 6, 242, 490, 512, 517, 519
hepatitis 310
hepatotropic viruses 312
paratyphoid A and B 455
prevention of 6
severe 458t
tuberculosis 434
uncomplicated 458t
vaccine 246t, 247t, 492, 495, 506, 517, 530
conjugate 506
Typhus fever 417
Tzanck method 325
U
Ulcers 556
decubitus 439
United Nations Children's Fund 22
United States Public Health Service 18
Universal Immunization Program 2, 19, 20, 292, 501
Universal vaccines 529
Upper respiratory tract 266
infection 157, 239
Ureaplasma 266
urealyticum 168, 266
Urethra, uncomplicated gonococcal infections of 556
Urethral discharge 554, 555
Urethral valves, posterior 201
Urethritis 267
nongonococcal 556
Urinary catheter 101
removing 123
Urinary retention 441, 444
Urinary tract infection 29, 68, 195, 199, 236, 545
catheter associated 108, 121, 122
diagnostic features 197
epidemiology 195
etiology 195
fungal 203
initial febrile 199fc
pathogenesis 195
recurrent 200
Urine
culture 75, 243
output 360
sample 555
Urogram, intravenous 200
Urosepsis 196
Urticaria 78, 267, 308
V
Vaccination
pre-exposure 467
primary 344, 345
principles of 469
schedule of 467
Vaccines 213, 245, 291, 331, 367, 464, 465, 499, 501, 502, 521, 536
against malaria, classification of 526
bacillus Calmette–Guérin 536
carriers 538
cell
culture 460, 464
killed 246
composition 336
conjugated 513
derived polio viruses 303
diphtheria
and tetanus 536
pertussis and tetanus 536
effectiveness 481
handling personnel 544
hepatitis B 536
immunogenicity 481, 505
immunology of 472
inactivated 470, 471, 507
injectable 486
live 476, 477, 513, 528
attenuated 470, 471, 507, 529, 530
recombinant 530, 531
lyophilized 464
maintenance of 466
measles 536
meningococcal 493, 495, 510, 517
oral poliomyelitis vaccine 536
pneumococcal 495, 508, 517, 518
pre-erythrocytic 526
preventable diseases 1, 2t, 25
reaction 482, 483, 484t
serious 482
refrigerator, maintenance of 540
regurgitation of 342
safety 292
schedule 336
sensitivities 536t
staphylococcal 533
storage
and handling 536
equipment supplied under immunization program 536
pattern 540f
tetanus toxoid 536
types of 186, 470
vial monitor 542, 543f
Vaginal discharge 554, 556
Vaginal infection 395, 397
Vaginosis, bacterial 556
Valacyclovir 186, 315, 316, 488
Valganciclovir 138
Vancomycin 34, 36, 98, 106, 133, 135, 165, 237, 443, 595
therapy, indications of 126
Varicella 84, 105, 130, 136, 143, 144, 324, 470, 475, 490, 497, 512, 513, 517, 519
diagnosis 144
epidemiology 143
gangrenosa 323
infection 5, 143
pneumonia 324
prevalence 5
prevention 144
prophylaxis 128
syndrome, congenital 143, 144
treatment 144
vaccine 492, 495, 506, 516, 517
zoster 168, 310, 323, 326
immunoglobulin 144, 326, 506
infection 84
virus 88, 104, 126, 180, 310, 323, 488
Vasculitis 423
Vastus lateralis 566
Vector-borne Disease Programs 452
Venereal disease research laboratory 145
Venezuelan equine encephalitis virus 180
Venous blood gases, monitoring of 361
Vero cell rabies vaccine, purified 464, 465, 511
Vesicle 78
Vesicoureteral reflux 195, 201
Vesicular impetigo 85
Vibrio cholerae 10, 206, 262, 433, 525, 530
Vincent's angina 439
Viral bronchiolitis, acute 327
Viral croup 164, 164t
severity, classification of 165
Viral disease 287, 423
Viral encephalitis 180182, 185
clinical features 182
diagnosis 183
epidemiology of 180
etiology 180
investigations 183
specific
diagnosis 184
treatment 185
Viral fever 364
Viral hepatitis
alanine aminotransferase 308
acute 305, 307, 308, 311
Viral infection 88t, 130, 133, 159t, 287, 553
acute systemic 297
wheeze-associated 328
Viral pneumonia 328
Viral respiratory illness, contagious 332
Viral vectors 529
Viremia 91, 318
Virosomes 525
Virus 48, 207, 294, 306, 332, 348
adeno-associated 318
hepatotropic 305
isolation of 138, 301
neutralization 53
nonhepatotropic 309, 312
spread 297
Visceral leishmaniasis 386, 446
Vitamins 158, 211, 288, 291
Vitek ESBL test 66
Voiding dysfunctions 195
Vomiting 242, 297, 300, 305, 366, 482
Voriconazole 126, 397
Vulvovaginal candidiasis 397, 557
Vulvovaginitis 553
W
War and natural disaster 222
Wart virus infection 372
Waste
final disposal of 41t
handling of 41
Water poison 348
Water soluble vitamins 312
Watery diarrhea 262
Wegener's granulomatosis 275
Weil's syndrome 427
Weil-Felix test 424
West Nile virus 180
Wheeze 328
Whipple's disease 55
Whipworm 405
White blood cell 176, 235, 257, 302, 319, 454
count 197, 235
peripheral 267
scans 235
Widal test 96, 244, 455
Wild poliovirus 19, 502
transmission 19
Wilson's disease 309, 311
Wimberger's sign 145
Wiskott-Aldrich syndrome 102, 103, 514
Wound management 260, 260t, 462t
X
X-linked immunodeficiency syndrome 103
Xylometazoline 160
Y
Yeast 49f
Yellow fever 471, 475, 520
vaccine 510
virus 306
Yersinia 206, 208, 212
enterocolitica 239, 433
Z
Zidovudine 134, 374, 375, 378, 379, 611, 617
Ziehl-Neelsen method 281
Ziehl-Neelsen stain 47, 48f, 272, 284, 284f
Kinyoun method of 47
Zikavirus 533
Zinc 211
deficiency 211, 414
Zoonotic disease 421, 430
Zoster vaccines 488
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General Topics1

A Parthasarathy
1.1 MAGNITUDE OF INFECTIOUS AND VACCINE-PREVENTABLE DISEASES IN CHILDREN AND ADOLESCENTS IN INDIA
A Parthasarathy, Hitt Sharma
 
INTRODUCTION
The WHO 2016 country specific report for India on prevalence of six vaccine-preventable diseases (VPDs), which were targeted for elimination in 1985 through the Universal Immunization Program, is alarming. Although majority of the states have achieved good control of these diseases through sustained and high immunization coverage, there are still many states in the North-Eastern region of the country which could achieve only 30–40% routine immunization coverage. These states with low immunization coverage levels contribute to the maximum number of reported VPDs cases, thus responsible for their heavy burden in the Indian country profile. Thanks to creativity, professionalism and perseverance in the National Polio Surveillance Program today, WHO has removed India from the list of polio-endemic countries in the world with the last case of polio reported from India as of January 13, 2010. However, regarding other pediatric infectious diseases, only little data is available due to lack of countrywide effective surveillance system.
 
DEMOGRAPHY
Table 1.1.1 depicts the demography and vital statistics figures pertaining to the years 1980–2016 with comparative figures for the years 1980, 1990, 2000 and 2012–2016.
 
REPORTED CASES
Table 1.1.2 depicts the number of reported cases of VPDs since the years 2012–2016 with comparative figures for the years 1980, 1990 and 2000.
Although there is a significant reduction in the total number of cases when compared to those in 1980s, it remains a matter of concern that still there are many preventable cases affecting children under 5 years, but this is just the “tip of the iceberg”.
Table 1.1.1   Demography and vital statistics figures (1980–2016).
Development developing status
GNI/capita (US$)
GDP/capita (US$)
1,590
6,089
Infant (under 12 months) mortality rate
Child (under 5 years) mortality rate
38
48
Population data in thousands
2016
2015
2014
2013
2012
2000
1990
1980
Total population
13,24,171
13,09,054
12,93,859
12,78,562
12,63,066
10,53,051
8,70,133
6,96,784
Live births
25,197
25,244
25,338
25,494
25,717
27,880
27,419
25,220
Surviving infants
24,277
24,291
24,348
24,461
24,635
26,057
25,021
22,372
Population less than 5 years
1,19,998
1,21,415
1,22,588
1,24,278
1,26,131
1,27,607
1,21,428
1,03,422
Population less than 15 years
3,73,356
3,75,145
3,76,631
3,78,168
3,79,513
3,65,774
3,30,036
2,73,442
Female 15–49 years
3,41,429
3,36,722
3,32,172
3,27,463
3,22,658
2,61,022
2,05,762
1,62,390
(GNI: gross national income; GDP: gross domestic product)
Source: WHO vaccine-preventable diseases: monitoring system 2017, India
2
Table 1.1.2   Number of reported cases of vaccine-preventable diseases in 1980, 1990, 2000 and 2012–2016.
2016
2015
2014
2013
2012
2000
1990
1980
Diphtheria
3,380
2,365
6,094
3,133
2,525
5,125
8,425
39,231
Japanese Encephalitis
1,627
1,620
1,657
1,078
Measles
71,726
90,387
79,563
13,822
18,668
38,835
89,612
1,14,036
Mumps
Pertussis
37,274
25,206
46,706
31,089
44,154
31,431
1,12,416
3,20,109
Polio*
0
0
0
0
0
265
10,408
18,975
Rubella
8,274
3,252
4,870
3,698
1,232
Rubella (CRS)
25
Neonatal Tetanus**
227
491
492
415
588
3,287
9,313
Total Tetanus
3,781
2,268
5,017
2,814
2,404
8,997
23,356
45,948
Yellow Fever
*Polio refers to all polio cases (indigenous or imported), including polio cases caused by vaccine derived polio viruses (VDPV). It does not include cases of vaccine-associated paralytic polio (VAPP) and cases of non polio acute flaccid paralysis (AFP).
**Neonatal Tetanus and Total Tetanus cases equality may be the result from a lack of non-Neonatal Tetanus surveillance system.
(CRS: congenital rubella syndrome)
Source: WHO vaccine-preventable diseases: monitoring system 2017, India
Many cases of measles, pertussis, diphtheria, etc. may still be missing in these reports due to under-reporting.
 
The Magnitude
 
Diphtheria
Around 3380 cases of diphtheria are reported in 2016 from various parts of the country despite the existence of National Immunization Mission since 1985. It is a matter of concern for the planners as well as the implementers. In the absence of subclinical infection in most parts of the country, any new case of diphtheria is bound to cause dreaded complications like diphtheritic myocarditis/neuroparalytic complications, etc.
In India, the state of Andhra Pradesh accounted for 40–70% of diphtheria cases reported from the country during 2003–2006, most of them being reported from Hyderabad, the state capital. In Hyderabad, diphtheria rate increased from 11 per 100,000 in 2003 to 23 per 100,000 in 2006. Integrated Disease Surveillance Programme (IDSP), National Centre for Disease Control (NCDC), Delhi, reported 7 outbreaks of diphtheria in India during the year 2014.
The 2016 surveillance data, which comes from the states of Bihar, Haryana, Kerala, and Uttar Pradesh (UP), shows the importance of examining subnational surveillance data and coverage (Table 1.1.3).
The age distribution of cases for these states is very different, with Bihar having the highest proportion of cases under 5, Kerala having the highest proportion of cases over 10, and Haryana and UP showing the highest proportion of cases between 5 and 10 years of age. Survey data demonstrate that the coverage for both DTP3 and the fifth dose at 5 years of age is also highly variable among regions.
Table 1.1.3   Age distribution of diphtheria cases in states of India with case-based surveillance, 2016.
State
Total cases
Under 5
5–10 years
Over 10 years
Bihar
71
41%
34%
25%
Haryana
59
27%
53%
20%
Kerala
556
8%
18%
74%
Uttar Pradesh
844
25%
53%
22%
Total
1530
20%
39%
41%
 
Pertussis Infection
Pertussis continues to be a major public health problem in both developing and developed countries. There is passive reporting of whooping cough cases from the public sector, the data is maintained by the Government of India and also shared with WHO. In India, the incidence of pertussis declined sharply after launch of Universal of Immunization Program (UIP). The shifting age group for new pertussis cases and complications in adolescents is a matter of concern. Pertussis in adolescents and adults is responsible for considerable morbidity in these age groups and also serves as a reservoir for disease transmission to unvaccinated/partially vaccinated young infants. It has become necessary to administer adolescent pertussis vaccine in areas endemic for pertussis.3
 
Tetanus
A total of 3,781 cases of tetanus (inclusive of 227cases of neonatal tetanus) stresses the need for a high diphtheria-tetanus-pertussis (DTP) coverage of under 1 and under 5 children as well as a high coverage of two doses of Td (toxoid dose) to pregnant mothers. Since neonatal tetanus invariably has a high case fatality rate, which adds to the total infant mortality, urgent steps are needed to step up the Td two-dose coverage to nearly 100% of all pregnant mothers. This schedule appears to provide protective levels of antibody for well above 80% of newborns. Both WHO and Indian Academy of Pediatrics Committee on Immunization recommend replacement of tetanus toxoid by Td vaccine in the National Immunization Program (NIP).
 
Measles
Estimates of measles-related deaths have been considered a crucial indicator to evaluate the progress of any nation towards measles elimination. The global estimates for the year 2013 suggest that close to 0.14 million deaths were attributed to measles, accounting for nearly 16 deaths each hour. Study findings have indicated that more than 50% of the global measles associated deaths were reported in India alone. India has made important efforts and gains against measles in recent years. Measles deaths have declined by 51% from an estimated 100,000 in the year 2000 to 49,000 in 2015. This has been possible by significantly increasing the reach of the first dose of measles vaccine, given at the age of nine months under routine immunization programme, from 56% in 2000 to 87% in 2015. The National Family Health Survey-4 (2015–2016) has assessed it to be 81.1%. This is low compared to the 95% coverage level required for elimination. Indian Association of Pediatrics (IAP) has revised its recommendations on Measles and MMR vaccination schedule. The new schedule will have a dose of MMR at 9 months instead of measles, and another dose (2nd) at 15 months of age. The earlier recommendation of 2nd dose of MMR at 4–6 years of age has been removed.
 
Poliomyelitis
India has made remarkable progress in the control and elimination of poliomyelitis. From an alarming number of nearly 2,000 cases in 1998, the case count as on September 17, 2010 was just 39 cases. Since January 13, 2011 nil case of polio due to wild poliovirus has been reported.
In 2009, India had more polio cases than any other country in the world (756). In just two short years, India has taken a giant step toward eradicating polio globally forever. On January 13, 2012, India reached a major milestone in the history of polio eradication—a 12-month period without any case of polio. The WHO reported that in 2011 India had its first polio-free year and is therefore no longer considered polio-endemic. This date marks the unprecedented progress in India and an endorsement of the effectiveness of the polio eradication strategies and their implementation in India. India is now off the WHO list of polio-endemic countries, but has to remain free of polio for the next 2 years to achieve the status of polio-free country.
The Strategic Plan was developed in response to the May 2012 World Health Assembly which declared the completion of poliovirus eradication to be a programmatic emergency for global public health. Under this plan to achieve and sustain a polio-free world, the use of OPV must eventually be stopped worldwide, starting with OPV containing type 2 poliovirus (OPV type 2). At least one dose of Poliomyelitis vaccine (Inactivated) must be introduced as a risk mitigation measure and to boost population immunity.
Since 25th April 2016 the Ministry of Health and Family Welfare, Government of India (GoI) switched from tOPV to bOPV. Now in India only bOPV will be used both in routine immunization (RI) as well as polio campaigns. To provide protection against type-2 poliovirus to naive children born post-switch. IPV would be the only source of providing type-2 immunity to children after April 2016.
 
Mumps Infection
Although we do not have the accurate figures of reported cases, it is evident from the cases seen by pediatricians and family physicians in their office practice that the number of mumps cases is also of a significant proportion in India. With the availability of a safe, effective, indigenous and cost-effective vaccine, mumps should be immediately included in the UIP as MMR vaccine in place of MR vaccine. Further, there is an urgent need of initiating surveillance of clinical cases of mumps all over the country and it should be declared as a ‘notifiable’ disease in India. IAP has recently revised its recommendations on MMR vaccination with first dose at 9 months in place of standalone measles vaccine, and second at 15 months of age.
 
Rubella Infection
Although the total number of cases of rubella is not known, rubella is the most common and single cause of blindness in the newborns as reported by ophthalmologists in India with cases of congenital rubella syndrome (CRS). A recent study conducted in both rural and urban areas of 12 districts in Maharashtra shows that rubella virus infection is prevalent in these areas and almost 25% girls reach childbearing age without acquiring natural immunity against the disease. Studies conducted across India suggest similar baseline information on the susceptibility profile of women of childbearing age.4
In order to raise the immunity against rubella and prevention of CRS, the following strategy is recommended:
Administration of first dose of rubella containing vaccine, viz. MMR, at 9 months and the second dose at the age 15–18 months and conducting mass immunization campaigns targeting girls up to the age of 15 years. The Ministry of Health and Family Welfare launched Measles Rubella (MR) vaccination campaign in the country in February 2017. The campaign against these two diseases will start from five States/UTs (Karnataka, Tamil Nadu, Puducherry, Goa and Lakshadweep) covering nearly 3.6 crore target children. Following the campaign, Measles-Rubella vaccine will be introduced in routine immunization, replacing the currently given two doses of measles vaccine, at 9–12 months and 16–24 months of age.
 
Hepatitis B Virus Infection
India is rated to be in the intermediate zone for hepatitis-B prevalence with hepatitis B surface antigen (HBsAg) prevalence between 2% and 10% among populations studied. The fact remains that hepatitis B infection occurs during childhood and causes fatal complications like hepatocellular carcinoma, chronic active hepatitis or cirrhosis of liver and thus accounting for high morbidity and mortality. In India the prevalence of Hepatitis B surface antigen (HBsAg) is 3–4.2% with over 40 million HBV carriers. Every year over 100,000 Indians die due to Hepatitis B complications.
Hepatitis B vaccine is safe and is highly effective in preventing hepatitis B virus (HBV) infection and its serious consequences. Protection afforded by this vaccine is long lasting. Numerous studies have shown that adding hepatitis B vaccine into the expanded program of immunization is highly cost-effective, even in areas with low HBV endemicity. In 1991, the Global Advisory Group of the Expanded Program on Immunization of WHO recommended that hepatitis B vaccine should be introduced into NIPs in all countries by the year 1997. The World Health Assembly approved this in 1992. More than 100 countries have already included this vaccine in their NIPs. In countries that have implemented universal childhood hepatitis B immunization, HBV carrier rate has declined markedly and incidence rate of long-term consequences, like liver cancer, have shown a decrease.
It is a matter of satisfaction that the Government of India has since introduced hepatitis B vaccine in the National Schedule in select pilot project areas from the year 2002 onward, which is now extended to the entire country in a phased manner. As per 2015 national estimates, the hepatitis B vaccination coverage of children is 45% for the birth dose (within 24 hours after birth) and 86% Hepatitis B third dose. Figure 1.1.1 depicts the magnitude of the disease at the global level and in India.
 
Hepatitis A Virus Infection
A disease of children has now shifted to adolescents. Although complications are less compared to hepatitis B infection, effective vaccines are now available to be given in prime-boost schedule. The actual incidence is not known since many cases of hepatitis A are not reported. May be with the introduction of Integrated Disease Surveillance Project (IDSP) in India, we will have more number of hepatitis A cases reported. IDSP identified a substantial number of hepatitis cases and outbreaks during 2011–2013. The large number of hepatitis A and E outbreaks might be explained in part by the lack of adequate sewage and sanitation systems; defecation in open fields, which can contaminate surface drinking-water sources, remains a common practice.
zoom view
Fig. 1.1.1: Geographic pattern of global hepatitis B prevalence.
5The large numbers of hepatitis A cases might also reflect an epidemiologic shift in the affected population in India. Hepatitis A infection during childhood often is asymptomatic and unrecognized, and typically confers lifelong immunity. With increasing age at time of infection, symptomatic cases become more common. With improved hygiene and sanitation reflecting India's improving economy, more children might escape childhood infection and remain susceptible to infection during adolescence and adulthood. The global geographic distribution is given in the Figure 1.1.2. The current recommendation is to administer hepatitis A vaccine at 12 months of age due to absence of maternal antibodies in the newborn. Killed Hep A vaccine: Start the 2-dose Hep A vaccine series for children aged 12 through 23 months; separate the 2 doses by 6–18 months. Live attenuated H2-strain Hepatitis A vaccine: Single dose starting at 12 months and through 23 months of age.
 
Varicella Infection
Varicella is widely prevalent mostly in children 5–10 years of age with increasing incidence in children under 5. A vaccine with good protective efficacy is available and is being used by many pediatricians all over the country. The disease usually manifests in early summer and it is estimated that many thousands of cases are not reported to the medical facility due to traditional beliefs and customs, and because of the lesser complications attributed to the disease, per se. However, the available statistics reveal the magnitude to some extent.
Varicella prevalence in India
  • Twenty-five million cases annually in India
  • Complications: Secondary infection—scars, encephalitis, cerebellitis, H. zoster, pneumonia, congenital varicella syndrome
  • Morbidity: School and office absenteeism
  • Mortality: 2–25 per 100,000, immunocompromised (IC): 10–30%
  • High risk groups include adults, IC host, pregnancy and neonate.
  • Following breakthrough infection in 30% of children who had received a single dose of varicella vaccine, the current recommendation is to administer two doses of varicella vaccine at 15 months and 5 years simultaneously with two doses of MMR vaccine.
 
Human Papillomavirus (HPV) Infection
Human papillomavirus (HPV) infection is now a well-established cause of cervical cancer and there is growing evidence of HPV being a relevant factor in other anogenital cancers (anus, vulva, vagina and penis) and head and neck cancers. HPV types 16 and 18 are responsible for about 70% of all cervical cancer cases worldwide. HPV vaccines that prevent against HPV 16 and 18 infection are now available and have the potential to reduce the incidence of cervical and other anogenital cancers.
Cancer of the cervix uteri is the 4th most common cancer among women worldwide, with an estimated 5,27,624 new cases and 2,65,672 deaths in 2012. Worldwide, mortality rates of cervical cancer are substantially lower than incidence with a ratio of mortality to incidence to 50.3%.
zoom view
Fig. 1.1.2: Geographic distribution of hepatitis A prevalence.
6Current estimates indicate that every year 1,22,844 women are diagnosed with cervical cancer and 67,477 die from the disease. Cervical cancer ranks as the 2nd most frequent cancer among women in India and the 2nd most frequent cancer among women between 15 and 44 years of age. About 5.0% of women in the general population are estimated to harbour cervical HPV-16/18 infection at a given time, and 83.2% of invasive cervical cancers are attributed to HPVs 16 or 18. Prophylactic HPV vaccination has provided a powerful tool for primary prevention of cervical cancer and other HPV-related diseases. Three HPV vaccines are now available: bivalent (against HPVs 16/18), quadrivalent (against HPVs 6/11/16/18) and the recently approved 9-valent vaccine (against HPVs 6/11/16/18/31/33/45/52/58). Two doses of HPV vaccine are advised for adolescent/preadolescent girls aged 9–14 years; for girls 15 years and older, current 3 dose schedule will continue. For two-dose schedule, the minimum interval between doses should be 6 months. Human Papillomavirus (HPV) vaccination program is directed towards the prevention of cervical cancer. Delhi is now the first state to launch the Human Papillomavirus (HPV) vaccine as a public health program for school children (9–13 years).
 
Typhoid
The disease is prevalent throughout the year and pediatricians and pediatric hospitals get typhoid cases almost throughout the year. Although conjugated vaccine is available, the protective efficacy is around 60% and paratyphoid infection is not protected by the conjugate polysaccharide vaccine. The best ways are to adopt universal precautions and personal hygiene for the protection of typhoid fever.
Prevention of typhoid
  • Five million cases annually in India
  • Severe morbidity, 1–2% mortality
  • Carrier state: Spread through food handlers
  • About 50–90% of Salmonella typhi are multidrug-resistant of late quinolone resistance—90%.
 
Tuberculous Meningitis or Encephalitis
The true incidence is not known. But the fact remains that private and public institutions admit very few cases of TB meningitis or encephalitis when compared to yesteryears due to good control of hematogenous spread of the disease in children with high coverage of bacille Calmette–Guérin (BCG) vaccine. Recent meta-analysis confirms the significant decline in the incidence of TB meningitis or encephalitis, miliary TB and disseminated TB.
 
Meningococcal Meningitis and Disease
Meningococcal meningitis or cerebrospinal fever occurs sporadically and in small outbreaks in most parts of the world. The zone lying between 5° and 15° N of the equator in tropical Africa is called the “meningitis belt” because of the frequent epidemic waves that have been occurring in that region. During recent years, several serious outbreaks affecting numerous countries occurred, not only in the so-called meningitis belt in Africa but also in both tropical and temperate zones of other continents, viz. Americas, Asia and Europe. WHO estimates that about 500,000 cases of meningococcal disease occur every year worldwide causing 50,000 deaths. The fatality of typical untreated cases is about 80%. With early diagnosis and treatment, case fatality rates have declined.
Before 2010 and the mass preventive immunization campaigns, Group A meningococcus accounted for an estimated 80–85% of all cases in the meningitis belt, with epidemics occurring at intervals of 7–14 years. Since then, the proportion of the A serogroup has declined dramatically. During the 2014 epidemic season, 19 African countries implementing enhanced surveillance reported 11,908 suspected cases including 1146 deaths, the lowest numbers since the implementation of enhanced surveillance through a functional network.
Meningococcal disease is endemic in India. N. meningitidis is the third most common cause of bacterial meningitis in India in children aged <5 years, and is responsible for an estimated 1.9% of all cases regardless of age. The majority of reported cases are due to serogroup A, with rare reports of serogroups B and C. Cases of meningococcal meningitis are reported sporadically or in small clusters. During 2007, about 4,472 cases of meningococcal meningitis were reported in India with about 252 deaths. The decision to undertake mass vaccination following an outbreak is based upon the attack rate within an area. During inter epidemic and epidemic periods, immunoprophylaxis of high-risk populations is implemented and chemoprophylaxis with antimicrobials is used for close contacts.
 
Invasive Hemophilus Influenzae Disease
Although the exact incidence of the magnitude of invasive H. influenzae and pneumococcal diseases is not known, hospital admissions clearly indicate that these two organisms significantly contribute to invasive diseases like pneumonia and meningitis.
Childhood pneumonia is the leading single cause of mortality in children aged less than 5 years. The incidence in this age group is estimated to be 0.29 episode per child-year in developing and 0.05 episodes per child-year in developed countries. This translates into about 156 million new episodes each year worldwide, of which 151 million 7episodes are in the developing world. Most cases occur in India (43 million), China (21 million) and Pakistan (10 million), with additional high numbers in Bangladesh, Indonesia and Nigeria (6 million each). Pneumonia is responsible for about 19% of all deaths in children aged less than 5 years, of which more than 70% take place in sub-Saharan Africa and South-East Asia.
Effective vaccines are now available for their control and IAP recommends Hib vaccine for routine use preferably in combination formulation of diphtheria-tetanus-whole cell pertussis-hepatitis B/Hib (DTPw-HB-Hib) at 6, 10 and 14 weeks.
Figure 1.1.3 depicts the global disease burden including India.
Estimated invasive Hib disease in India: Based on community-based report:
  • Meningitis 17 per 100,000 children per annum
  • Pneumonia 1.5 times meningitis: 25 per 100,000 children per annum
  • Total invasive disease: 42 per 100,000 per annum
  • Hib disease per 100,000: 266–1,750
  • Children below 5 years (15% of total population) 15, 40, 52, 287
  • Total estimates in India: 409,640–2,695,000
Case fatality due to invasive Hib diseases
  • If CFR 2%: 8,192–53,900 per annum
  • If CFR 10%: 40,964–269,500 per annum
Studies reporting invasive Hib disease are limited.
Reported from all parts of India:
  • Hib pneumonia: 2–33%
  • Hib meningitis: 2–35%
  • Almost half of the children are colonized with Hib
  • Agent is present in abundance
  • Risk factors for increased invasive Hib disease exist in India.
(Source: IAP Immunization update; 2006.)
The proposal to include pentavalent DTPw-HB-Hib vaccine formulation in NIP was recommended by National Technical Advisory Group on Immunization (NTAGI) and approved by the central cabinet to bring down the Hib disease burden in India. Government of India has successfully implemented mass immunization program with pentavalent vaccine, which is now introduced in all the states of India. The use of pentavalent vaccine automatically raises the coverage level of hepatitis B and hib vaccines. If the vaccines are given individually, the coverage of hepatitis B and hib vaccines usually lags behind DPT coverage. This gap can be filled by using pentavalent vaccine in routine immunization program.
 
Pneumococcal Disease
Pneumonia is the single largest infectious cause of death among under-five children worldwide, accounting for about 0.92 million deaths in 2015. It is estimated that 1 in 6 deaths in under-five children was due to pneumonia in 2015. Pneumococcal pneumonia in particular is a major public health concern for children globally. This infection accounts for 18% of all severe pneumonia cases and 33% of all pneumonia deaths worldwide. More than 80% of deaths associated with pneumonia occur in children during the first two years of life. Pneumococcal disease is also the number one vaccine-preventable cause of death in children under five, globally and in India (Fig. 1.1.4).
zoom view
Fig. 1.1.3: Global Hib incidence rate.Source: WHO decision-making and implementation of conjugate Hib vaccines (NUVI); 2009
8
zoom view
Fig. 1.1.4: Percentage of deaths among children under age 5 attributable to pneumonia, 2015.Source: WHO and Maternal and Child Epidemiology Estimation Group (MCEE) provisional estimates 2015 http://data.unicef.org/child-health/pneumonia.html#sthash.D7850ssq.dpuf
Incidence of invasive pneumococcal diseases:
  • Around 12–35% of all admissions are due to LRT in India. In 2010, 3.6 million episodes of severe pneumonia and 0.35 million all-cause pneumonia deaths occurred in children under the age of 5 years in India. Among those, 0.56 million episodes of severe pneumonia (16%) and 0.10 million deaths (30%), respectively, were caused by pneumococcal pneumonia. India has a pneumonia mortality rate of 7 per 1000 live births.
  • Streptococcus pneumococcus is the cause for 50% of community acquired pneumonia, 20–40% of all pyogenic meningitis.
  • The rate of invasive pneumococcal disease: 167/100,000 less than 2 years in USA (before vaccination), 224–349/100,000 less than 5 years in developing countries.
The ten countries with the highest numbers and proportions of pneumococcal cases were all in Asia and Africa; they account for 66% (44–88%) of pneumococcal cases worldwide (India 27%, China 12%, Nigeria 5%, Pakistan 5%, Bangladesh 4%, Indonesia 3%, Ethiopia 3%, Congo 3%, Kenya 2% and the Philippines 2%). Of the 14.5 million pneumococcal cases, 95.6% were cases of pneumonia, 3.7% nonpneumonia, nonmeningitis invasive pneumococcal syndromes and 0–7% meningitis.
Pneumococcal deaths in children aged 1–59 months per 100,000 children younger than 5 years (HIV-negative pneumococcal deaths only). The boundaries shown and the designations used on this map do not imply the expression of any opinion by WHO concerning the legal status of any country, territory, city or area, or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines in Figure 1.1.5 represent approximate border lines for which there may not yet be full agreement.
The new 13 valent pneumococcal vaccine, offers about 70–75% protection against the prevalent strains in India. In May 2017, Government of India decided to include pneumococcal conjugate vaccine (PCV) in UIP in a phased approach. With this phased introduction, nearly 2.1 million children in 3 states will be vaccinated with PCV in the first year. The coverage will be expanded across the entire country in the coming years.
 
Acute Diarrheal Diseases
Diarrhea is a leading killer of children, accounting for 9% of all deaths among children under age 5 worldwide in 2015. This translates to over 1,400 young children dying each day, or about 526,000 children a year, despite the availability of simple effective treatment.
Figure 1.1.6 depicts the global disease burden including India.
In India, diarrheal disease is a major health problem. More than 300 million episodes of acute diarrhea occur every year in children under 5 years of age. During 2005, about 1.07 million cases of acute diarrhea were reported in India with 2,040 deaths. The actual incidence must be many fold. The National Diarrhoeal Disease Control Programme has made a significant contribution in averting deaths among children under 5 years of age. Much attention has been given to acute diarrhea and its management over the last decade, which is dominated by advances in oral rehydration techniques.9
zoom view
Fig. 1.1.5: Ten countries with the greatest number of pneumococcal deaths in children aged 1–59 months.Source: Lancet. Vol 374 September 12, 2009.
Bubble size indicates the number of pneumococcal deaths.
Country (number of deaths): India (142,000), Nigeria (86,000), Ethiopia (57,000), Democratic Republic of the Congo (51,000), Afghanistan (31,000), China (30,000), Pakistan (27,000), Bangladesh (21,000), Angola (20,000) and Uganda (19,000)
zoom view
Fig. 1.1.6: Percentage of deaths among children under age 5 attributable to diarrhea, 2015.Source: WHO and Maternal and Child Epidemiology Estimation Group (MCEE) provisional estimates 2015
The rotavirus, first discovered in 1973, has emerged as the leading cause of severe, dehydrating diarrhea in children aged under 5 years globally, with an estimated more than 25 million outpatient visits and more than 2 million hospitalizations attributable to rotavirus infections each year. In developing countries, three-quarters of children acquire their first episode of rotavirus diarrhea before the age of 12 months, whereas in developed countries the first episode is frequently delayed until the age of 2.5 years. The new rotavirus vaccines are now introduced for routine use in a number of industrialized and developing countries. The NTAGI have recommended the introduction of Rotavirus vaccine with GAVI subsidy in the NIP in a phased manner.
India has made steady progress in reducing deaths in children younger than 5 years, with total deaths declining from 2.5 million in 2001 to 1.5 million in 2012. This remarkable reduction was possible due to the inception and success of many universal programs like expanded program on immunization, program for the control of diarrheal diseases and acute respiratory infection. Even though the deaths among children under-5 years have declined, the proportional mortality accounted by diarrheal diseases still remains high. Diarrhea is the third most common cause of death in under-five children, responsible for 13% deaths in this age-group, killing an estimated 3,00,000 children in India each year.10
 
Cholera
Cholera is an acute diarrheal infection caused by ingestion of food or water contaminated with the bacterium Vibrio cholerae. Cholera remains a global threat to public health and an indicator of inequity and lack of social development. Globally, the actual number of cholera cases is known to be much higher; the discrepancy is the result of under reporting and inconsistency in case definition and lack of standard vocabulary. Some countries report laboratory confirmed cases only, and so many cases are labeled as acute watery diarrhea. Researchers have estimated that every year, there are roughly 1.3 to 4.0 million cases, and 21,000 to 1,43,000 deaths worldwide due to cholera. Epidemics of cholera are frequent, striking adults as well as children.
India accounts for 675,188 cases and 20,256 deaths. In addition, an issue of concern is that 65–86% of the isolates have been found to be resistant to the commonly used antimicrobials and their prevalence is concentrated in the lowest quintile of wealth. In India, during 2005, the larger endemic foci of cholera were found in Delhi (945 cases), Tamil Nadu (724 cases and one death), West Bengal (235 cases), Andhra Pradesh (165 cases), Karnataka (214 cases and one death), Kerala (27 cases and one death) and Gujarat (82 cases and two deaths). The total number of cases reported was 3,156 with six deaths. In the year 2008, WHO has recorded 2,680 cases of cholera in India.
The most effective prophylactic measure is health education directed mainly to: (a) effectiveness and simplicity of oral rehydration therapy; (b) benefits of early reporting for prompt treatment; (c) food hygiene practices; (d) hand washing after defecation and before eating; and (e) benefits of cooked, hot foods and safe drinking water. Since cholera is a disease of the poor and ignorant, these groups should be tackled first.
Although, a parenteral cholera vaccine of Ogawa and Inaba serotypes of V. cholerae is available, there are still doubts about its usefulness as a preventive measure. The oral cholera vaccine now available in India is recommended for routine use in cholera endemic regions.
 
Diarrheal Diseases Control Program
The incidence of cholera cases and deaths has decreased in recent years. Oral rehydration therapy program was started in 1986–87 in a phased manner. The main objective of the program is to prevent diarrhea-associated deaths in children due to dehydration. The program highlights the rational management of diarrhea in children, including increased intake of home available fluids, zinc supplementation and breastfeeding. Oral rehydration solution (ORS) is being supplied as a part of subcenter kits and is promoted as a first line of treatment.
India has made steady progress in reducing deaths in children younger than 5 years, with total deaths declining from 2.5 million in 2001 to 1.5 million in 2012. This remarkable reduction was possible due to the inception and success of many universal programs like expanded program on immunization, program for the control of diarrheal diseases and acute respiratory infection. Even though the deaths among children under-5 years have declined, the proportional mortality accounted by diarrheal diseases still remains high. Diarrhea is the third most common cause of death in under-five children, responsible for 13% deaths in this age-group, killing an estimated 300,000 children in India each year.
 
Malaria
At present, about 109 countries in the world are considered endemic for malaria, 45 countries within WHO African region. There were an estimated 216 million episodes of malaria in 2010, with a wide uncertainty interval (5th–95th centiles) from 149 million to 274 million cases. Approximately 81%, or 174 million (113–239 million) cases, were in the African region, with the South-East Asian Region (SEAR) accounting for another 13%.
There were an estimated 655,000 (5,37,000–9,07,000) malaria deaths in 2010, of which 91% (596,000, range 4,68,000–8,37,000) were in the African Region. Approximately 86% of malaria deaths globally were of children under 5 years of age.
In the SEAR, during 2009, a total of 2.7 million confirmed malaria cases and 3,188 malaria deaths were reported whereas estimated malaria cases were around 26–36 million and malaria deaths between 42,300 and 77,300. The highest number of laboratory confirmed cases were reported from India (15,63,344) followed by Indonesia (5,44,470) and Myanmar (4,14,008) whereas the lowest number of cases was reported from Sri Lanka (558) followed by Bhutan (972) and Nepal (3,335). In case of malaria deaths, the highest number of deaths were reported from India (1,133) followed by Myanmar (972) and Indonesia (900).
In India, malaria continues to pose a major public health threat, particularly due to plasmodium falciparum which is prone to complications. Experts estimate that more than 1.5 million persons are infected with malaria every year. The most affected states are North-Eastern states, Chhattisgarh, Jharkhand, Madhya Pradesh, Orissa, Andhra Pradesh, Maharashtra, Gujarat, Rajasthan, West Bengal and Karnataka. However, the other states are also vulnerable with local and focal outbreaks of malaria. Much of these areas are remote and inaccessible, fore or forest fringed with operation difficulties and predominantly inhabited by tribal population.
Despite these challenges, India is working – and making progress towards the elimination of malaria. Since 2000, the country has more than halved the number of malaria cases, down from 2 million to 8,82,000 in 2013 and, the 11trend is continuing. To reach pre-elimination, all states in India will need to have annual parasite incidence (API) of less than 1 per 1000 and all districts within the state will also need to be less than 1. Currently, 74% of India's more than 650 districts have achieved an API of less than 1. Strong financial support, increased surveillance, more health workers, and further program integration in all levels of the health system will be needed for the country to reach elimination.
Currently, there is no vaccine available, but research is going on for a vaccine to prevent infection and/or ameliorate disease. Unlike other vaccines, a malaria vaccine even with only 50% efficacy would still be very useful in controlling the disease. The time-bound objectives set out for the Eleventh (XIth) Five-Year Plan by Ministry of Health (MoH) and Family Welfare, Government of India (GoI) is reduction of malaria mortality rate by 50% up to 2010 and an additional 10% by 2012.
 
Japanese Encephalitis
Japanese Encephalitis (JE) is mosquito-borne encephalitis infecting mainly animals and incidentally man. Twenty-five years ago, JE was known as an endemic disease in East Asia, especially in Japan, China and Korea but in recent years, it has spread widely in South-East Asia, and outbreaks of considerable magnitude have occurred in Thailand, Indonesia, Vietnam, India, Myanmar and Sri Lanka.
An estimated 50,000 cases of JE occur globally each year, with 10,000 deaths and nearly 15,000 disabled. About three-quarters of the cases occur in the Western Pacific countries, primarily China and adjacent countries, with the remainder occurring in South-East Asia, especially India.
In India, the states reporting repeated outbreaks are Andhra Pradesh, Assam, Bihar, Haryana, Karnataka, Kerala, Maharashtra, Manipur, Tamil Nadu, Uttar Pradesh and West Bengal. The population at risk is about 300 million. The incidence of JE in India is still increasing, and the case-fatality rate of reported cases is high, i.e. 10–30%. India currently has no national vaccination program, but the MoH has recently drawn up a plan in which children 1–12 years of age will be immunized. In Tamil Nadu and Uttar Pradesh, immunization programs are already running; thus, JE incidence might stabilize in those regions. However, overall trends for India are difficult to predict because JE endemicity is heterogeneous and because socioeconomic conditions for control differ substantially from one state to another. As per the recent figures from WHO (2008), there have been 294 cases of JE reported in India.
According to the Directorate of National Vector Borne Disease Control Programme (NVBDCP), Delhi, 1661 cases of JE were reported in the year 2014 from 15 states and union territories, out of which 293 (17.6%) died. Assam, West Bengal, Uttar Pradesh (UP) and Jharkhand reported maximum number of cases.
Following mass vaccination campaigns with live attenuated SA-14-14-2 JE vaccine among pediatric age group, adult JE cases have outnumbered pediatric cases in some JE endemic states, including Assam. This led the state government of Assam to conduct special campaigns of JE vaccines in adults (>15 years) in some most affected districts. The exact reason behind this shift in age group is not well understood. On 3rd July, 2014 the Government of India (GOI) announced the introduction of four new vaccines, including JE vaccine, in the National immunization program. Recently, NVBDCP has identified 20 high burden districts in three states—Assam, Uttar Pradesh, and West Bengal, for adult JE vaccination (>15–65 years).
 
Tuberculosis
It remains a worldwide public health problem. It is estimated that about one-third of the current global population is infected asymptomatically with tuberculosis (TB). Most new cases and deaths occur in developing countries where infection is often acquired in childhood. The annual risk of TB infection in high-burden countries is estimated to be 0.5–2%.
India is the highest TB burden country in the world and accounts for nearly one-fifth (20%) of global burden of TB, two-thirds of cases in SEAR. Of the 9.2 million cases of TB that occur in the world every year, nearly 1.9 million are in India. Two out of every five Indians are infected with TB bacillus. In India, almost 0.37 million people die every year.
India accounts for one fourth of the global TB burden. In 2015, an estimated 28 lakh cases occurred and 4.8 lakh people died due to TB. The table below shows the estimated figures for TB burden globally and for India reported in WHO Global TB Report for the year 2015 (Table 1.1.4).
An estimated 1.3 lakh incident multi-drug resistant TB patients emerge annually in India which includes 79000 MDR-TB patients estimates among notified pulmonary cases. India bears second highest number of estimated HIV associated TB in the world. An estimated 1.1 lakh HIV associated TB occurred in 2015 and 37,000 estimated number of patients died among them.
DOTS-Plus for the management of drug resistant TB in India had been launched in 2007. There was then very limited progress between 2007 and 2009.
Table 1.1.4   Estimated figures for TB burden globally and for India reported in WHO Global TB Report 2015
Estimates of TB burden (2015)
Global
India
Incidence TB cases
104 lakh
28 lakh
Mortality of TB
14 lakh
4.8 lakh
Incidence HIV TB
11.7 lakh
1.1 lakh
MDR-TB
4.8 lakh
1.3 lakh
12But by 2009, it was planned that by the end of 2011 the drug resistant TB services would be available across India. The DOTS-Plus services (now referred to as the “Programmatic Management of Drug Resistant TB”) had been expanded across the whole country by 2012 and the service was available in all districts by 2013. By 2013 it had though been decided to decentralise the DOTS Plus services. The services were to be totally integrated into the main Revised National TB Control Programme (RNTCP) services at local level. In 2015, a total of 9,132,306 cases of suspected TB were examined by sputum smear microscopy and 1,423,181 people were diagnosed and registered for TB treatment by government's RNTCP.
The current vaccine strains are all descendants of the original Mycobacterium bovis isolate that Calmette and Guérin passaged through numerous cycles during the 13-year period, 1909–1921. Although, a number of BCG vaccine strains are available, in terms of efficacy, no BCG strain is demonstrably better than another, and there is no global consensus as to which strain of BCG is optimal for general use. Following closure of BCG vaccine laboratories in India, the GoI is using the BCG vaccine manufactured by Serum Institute of India Ltd., Pune, and Green Signal Bio Pharma Ltd. in its NIP.
The objective set out for TB control by MoH and Family Welfare, GoI, is to maintain 85% cure rate through entire mission period and also sustain planned case detection rate.
 
AIDS/HIV Infection
The acquired immunodeficiency syndrome (AIDS) is a fatal illness caused by human immunodeficiency virus (HIV) which breaks down the body's immune system, leaving the victim vulnerable to a host of life-threatening opportunistic infections, neurological disorders or unusual malignancies. Acquired immunodeficiency syndrome refers to the last stage of the HIV infection and can be called a modern pandemic affecting both industrialized and developing countries (Table 1.1.5).
Table 1.1.5   Number of people infected with human immunodeficiency virus infection and acquired immunodeficiency syndrome-related deaths.
Number of people living with HIV in 2008
Total: 33.4 million
Adults: 31.3 million
Women (aged 15 and above): 15.7 million
Children (under 15 years): 2.1 million
People newly infected with human immunodeficiency virus in 2008
Total: 2.7 million
Adults: 2.3 million
Children (under 15 years): 4,30,000
AIDS-related deaths in 2008
Total: 2.0 million
Adults: 1.7 million
Children (under 15 years): 2,80,000
Since the beginning of the epidemic, more than 70 million people have been infected with the HIV virus and about 35 million people have died of HIV. Globally, 36.7 million [34.0–39.8 million] people were living with HIV at the end of 2015. An estimated 0.8% [0.7–0.9%] of adults aged 15–49 years worldwide are living with HIV, although the burden of the epidemic continues to vary considerably between countries and regions. Sub-Saharan Africa remains most severely affected, with nearly 1 in every 25 adults (4.4%) living with HIV and accounting for nearly 70% of the people living with HIV worldwide (Fig. 1.1.7).
In Asia, an estimated 4.9 million (4.5–5.5 million) people were living with HIV in 2009. In 2009, an estimated 300,000 (260,000–340,000) people died of AIDS-related illnesses. Asia, home to 60% of the world's population, is second only to sub-Saharan Africa in terms of people living with HIV.
As per the recently released, India HIV Estimation 2015 report, National adult (15–49 years) HIV prevalence in India is estimated at 0.26% (0.22–0.32%) in 2015. In 2015, adult HIV prevalence is estimated at 0.30% among males and at 0.22% among females. Among the States/UTs, in 2015, Manipur has shown the highest estimated adult HIV prevalence of 1.15%, followed by Mizoram (0.80%), Nagaland (0.78%), Andhra Pradesh and Telangana (0.66%), Karnataka (0.45%), Gujarat (0.42%) and Goa (0.40%). Besides these States, Maharashtra, Chandigarh, Tripura and Tamil Nadu have shown estimated adult HIV prevalence greater than the national prevalence (0.26%).
Until a vaccine or cure for AIDS is found, the only means at present available is health education to enable people to make life-saving choices. All mass media channels should be involved in educating the people on AIDS, its nature, transmission and prevention. The development of drugs (antiretrovirals) that suppress the infection rather than its complications has been an important achievement. These antiretroviral chemotherapy, while not a cure, have proved to be useful in prolonging the life of severely ill patients.
 
Dengue Illness
This disease is essentially a tropical one and is endemic in large parts of Latin and South America. Of late, its incidence has been on the increase in Asian countries such as India. A large number of infections may be subclinical, that is, the patients may not even be aware that they have had the disease. Treatment is usually supportive and symptomatic. Most patients will recover without any sequel. The overall mortality rate with effective treatment is close to 1% but this may be higher in children. A vaccine is in the late stages of development, but is still not available for commercial use on a large scale. Control of the mosquito population reduces the incidence of dengue, yellow fever and certain other rare fevers that are also transmitted by the same species of mosquito.13
zoom view
Fig. 1.1.7: A global view of human immunodeficiency virus infection. Globally, 36.7 million [34.0–39.8 million] people were living with HIV at the end of 2015.Source : http://www.who.int/gho/hiv/en/
As per the information from the Director, India's National Vector-borne Disease Control Programme, a total of 12,000 cases and 50 deaths have been reported in the country until October, 2010. These figures are as per the reported cases from the states/UTs and the number of actual infections is likely to be far higher.
The time-bound objectives set out for the Eleventh (XIth) Five-Year Plan by MoH and Family Welfare, GoI, is reduction of dengue mortality rate by 50% up to 2010 and sustaining at that level until 2012.
Also in 2015, Delhi, India, recorded its worst outbreak since 2006 with over 15 000 cases. In 2016, till month of September, 39,771 cases and 78 deaths were reported in India.
WHO recommends that countries should consider introduction of the dengue vaccine CYD-TDV only in geographic settings (national or subnational) where epidemiological data indicate a high burden of disease.
 
Chikungunya Fever
A dengue-like disease and manifested by high fever and severe excruciating articular pains in the limbs and spinal column. There was an outbreak of this disease in Kolkata in 1963–1964 and another in Chennai in 1965, which gave rise to 300,000 cases in Chennai city alone.
The disease has reappeared after 41 years. During 2006, there was a large outbreak of chikungunya in India, with 1.39 million officially reported cases spread over 16 states; attack rates were estimated at 45% in some areas. The outbreak was first noticed in Andhra Pradesh and it subsequently spread to Tamil Nadu, Kerala and Karnataka, and then northward as far as Delhi. The other states involved were Maharashtra, Madhya Pradesh, Gujarat, Rajasthan, Puducherry, Goa, Orissa, West Bengal, Uttar Pradesh, Andaman and Nicobar Islands. During 2007, until 12th October, a further 37,683 cases had been reported by the Government of India. In the year 2010, again thousands of people have been reported to be diagnosed with the virus.
Currently in 2016, big upsurge/epidemic due to Chikungunya is going on in Delhi and cases being reported from other States/UTs too. Till, 11th September, 2016 a total of 14,656 clinically suspected cases (including 1724 in Delhi) from 18 states and 2 UT's have been reported.
 
Swine Flu
It is a respiratory infection and transmission is through contact with respiratory secretions from an infected person who is coughing or sneezing. The symptoms are similar to seasonal flu but with a higher intensity. The patient may present with high grade fever (≥38°C), cough, sore throat, runny or stuffy nose, body aches, lack of appetite, lethargy, headache, chills and fatigue. In addition, nausea, vomiting and diarrhea have been reported (higher rate than for seasonal flu). It was first noted in Mexico in March-April, 2009, and then rapidly spread to the US, Canada and throughout the world. More than 214 countries reported laboratory confirmed cases, including more than 18,366 deaths. In India, since 2009 until September 26, 2010, out of the total 44,350 laboratories-confirmed cases of swine flu there have been more than 2,500 deaths reported (Source: www.mohfw-h1n1.nic.in).
A resurgence of swine flu in several states of India has caused a considerable concern in 2012. Fresh outbreaks of the dreaded virus surfaced in Maharashtra, Rajasthan and some other states claiming at least 21 lives from January till March, 2012.14
zoom view
Fig. 1.1.8: Percentage of respiratory specimens that tested positive for influenza.Source: http://www.who.int/influenza/surveillance_monitoring/updates/latest_update_GIP_surveillance/en/
At least 309 cases were reported in five states including Andhra Pradesh, Karnataka and Gujarat, according to the latest health ministry figures.
Of the total 21 deaths in 2012 so far, Maharashtra has reported nine deaths, followed by seven in Rajasthan and five in Andhra Pradesh. No death has taken place in Karnataka and Gujarat, which have also reported cases of H1N1 virus (Fig. 1.1.8).
In 2014, a total of 218 people died from the H1N1 flu, India recorded 837 laboratory confirmed cases in the year.
Every year, there was a rise in number of cases and deaths during winter as temperature affects virus. During 2014–15 winter, there was a spurt in cases at the end 2014. In 2015, the outbreak became widespread through India. On 12 February 2015, Rajasthan declared an epidemic.
The WHO now considers swine flu also as a seasonal epidemic and has recommended to the global and indigenous flu vaccine manufacturers to manufacture combined seasonal and swine flu vaccine. Accordingly, all WHO prequalified laboratories manufacturing flu vaccines have come out with their combined pH1N1 and the seasonal H3N2 A and B strains of the flu vaccines. For the prevention of swine flu, there are two types of vaccines which are available in the market: (1) live attenuated influenza vaccine—a nasal spray and (2) an inactivated vaccine—injection.
Statistics from sentinel centers may reveal the incidence of other infectious diseases, which are not reliable as they represent only the “tip of the iceberg”. The need for establishing a Center for Disease Control, like the CDC, Atlanta and the effective monitoring of the IDSP, may help in knowing the exact disease burden in India.
 
FUTURE OF VACCINE PREVENTABLE DISEASES SURVEILLANCE IN INDIA
  • The incidence of diphtheria, pertussis, tetanus (including neonatal tetanus), measles is still a matter of concern despite the implementation of NIP since 1985.
  • A nationwide high coverage to near 100% in routine immunization is the need of the hour in India.
  • The IDSP is a welcome project, but alternately the establishment of a CDC and subsequent guidelines from time-to-time for disease control are the ideal measures for activity control and elimination of infectious diseases in India.
  • The updation of immunization practices by the Government and Professional agencies periodically with introduction of new vaccines like pneumococcal, HPV, etc. should also be expedited.
 
ACKNOWLEDGMENT
The authors are indebted to Dr Sameer Parekh and Dr Pramod Pujari, Serum Institute of India Pvt. Ltd., Pune, India, for help rendered in the preparation of this section.
 
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16
1.2 INFECTIOUS DISEASES SURVEILLANCE IN INDIA
T Jacob John
 
INTRODUCTION
The dictionary meaning of the word surveillance is “close observation of a suspected spy or criminal”. Close observation of diseases in the community—occurrence, numbers and outbreaks—provides clues about the culprits, the causative pathogens. There is thus a parallel between police intelligence in surveillance for protecting citizens against crimes and epidemiological intelligence through disease surveillance for protecting people from infectious diseases, particularly outbreaks. Epidemiological investigation after getting information about diseases through surveillance is, in fact, a form of detective work. Although diseases are kept under surveillance, their causative agents are the target of surveillance.
The World Health Organization (WHO) defines disease surveillance as: “the ongoing systematic collection, collation, analysis and interpretation of data [on diseases], followed by the dissemination of information to those who need to know in order that action may be taken”. In other words, disease surveillance is required for public health action for disease prevention or control. If appropriate action does not follow, the mere collection of information is insufficient to qualify as surveillance as it may serve only the purpose of statistics for administrative understanding, but not that of public health. So, in short, surveillance is “systematic collection of information on diseases for public health action to prevent or control them.” Therefore, it is often referred to as “public health surveillance”. The data collected through public health surveillance will identify diseases to be prioritized for control if not already identified for control. The data will also form the basis of systematic monitoring of the degree of control being achieved year to year.
True public health surveillance has two characteristics—continuity in time and coverage in space. If there are gaps, infectious agents may cause sporadic cases or even outbreaks undetected by the designated staff. Collection of data on the incidence or prevalence of non-infectious diseases is through other methods—such as case registries, surveys of population samples, cumulating hospital statistics, etc. However, many use the term surveillance, inexactly, for other forms of data collection on health conditions, risk factors, etc. or for discontinuous collection of data on infectious diseases. In other words, the term surveillance is often loosely used for various methods of collection of data, diluting its definitional meaning. Therefore, it will be difficult now to restrict its usage strictly according to definition. In each context, it is necessary to redefine surveillance or at least understand that the term is not used according to the precise definition.
The several common usages of the term surveillance have been presented in this chapter. In most such situations the main deficiency is the lack of the requirement of public health action following data collection. As India does not have a public health infrastructure that can respond adequately to surveillance information, true surveillance as practiced in countries with public health infrastructure is not easy. Therefore, collection of data remains in many situations only for statistical purposes, as has been illustrated. Only very few diseases or their infectious agents are kept under surveillance for monitoring progress of control and for responding with public health action. They have been described in detail.
 
PASSIVE AND ACTIVE SURVEILLANCE
Disease surveillance is classified as passive and active. In countries with public health infrastructure, there would be a set-up for surveillance in all population units (such as districts). It is usually manned by a district officer of public health and supporting staff—epidemiologist, data management expert, laboratory personnel and field staff. The surveillance system has the afferent limb (incoming) for data receiving, a central processing unit (under the public health officer) and efferent limb (outgoing) for investigations and containment actions. This set-up is clearly separated from that which provides medical care to those who become ill. The latter is called healthcare and the former is called public health. Healthcare may be organized in the public sector or in the private sector. Many countries, such as India, have a mix of public and private sector hospitals and clinics and private practitioners, all providing healthcare services on demand. Public health infrastructure, on the other hand, is possible only in the public sector as it requires designated staff free of any responsibility for healthcare, and with legal authority for the officer and staff for enforcing disease surveillance and entering premises for disease investigations or control activities. Government funds staff salaries and all overhead expenses.
Sick people come to the attention of healthcare personnel who diagnose the diseases and treat. There would be a list of specific diseases that have been ‘notified’ (by the health ministry of the government) for surveillance. When a healthcare provider working in public or private sector sees a person with any notified disease, he/she is required (by law) to report that fact to the designated public health official. When all hospitals, clinics and medical practitioners report cases of notified diseases, the public health agency receives, passively so to say, continuous information on the occurrence and distribution of such cases. This method of disease reporting is called “passive surveillance”. In India, every state has a list of notified diseases and the requirement for reporting on their statute books, but in the absence of public health infrastructure 17surveillance is not enforced. Instead, several ad hoc procedures are practiced for specific disease problems and they remain fragmented but not integrated. In many countries, passive disease surveillance is supplemented by passive reporting of laboratory evidence of specific pathogens infecting any patient.
Imagine that the local public health officer receives a few reports on cholera in a short interval of time, scattered within the community. The officer takes immediate action for searching for unreported cases in the community in order to understand the full extent of the outbreak. Public health staff may now visit all hospitals to check if unreported cases of cholera are admitted and, if any, with cholera-like illness had been seen in the outpatient service, etc. This is an active process, so to say. This is “active surveillance” in which the personnel of the public health agency go out in active search of cases. Information on all cases is required to define the geographic perimeter of the outbreak and to identify risk factors—perhaps the municipal water supply going to a few wards or another common source from which many families had drawn water was the channel of transmission of the pathogen. Further investigations on the quality of water would be done immediately and the contaminated supply would be stopped and disinfected in order to intercept the outbreak. Active surveillance is usually short-lived; once the problem is under control, the system reverts to passive surveillance, which is continuous without break. Often active surveillance is a part of the epidemiological investigations triggered by the detection of a signal from passive surveillance. When a disease is under elimination, active surveillance may become necessary to ensure no case was missed by failure of passive surveillance.
Another way to look at passive and active surveillance is to determine who generates data and how. The nodal agency for disease surveillance is local level (district or city) public health, with its personnel—the public health officer and trained staff. When they search for disease cases, the process is active—for active surveillance. When they receive reports from healthcare personnel, the nodal agency is the passive recipient—in passive surveillance. Passive surveillance per se costs little since healthcare workers earn their income from serving individual patients; their detecting and reporting notified diseases are incidental to their professional work and the only cost involved is postage for mailing the report or for electronic reporting. Those expenses are borne by the public health system—usually by supplying disease reporting forms and post-paid envelopes for enclosing the reports.
 
THE ROLE OF LABORATORY IN SURVEILLANCE
Although diseases are kept under surveillance, their causative agents are the target of surveillance. Every infectious disease has a specific etiology. In India, the demand for identifying etiology by laboratory testing in healthcare is low for two reasons: (1) patients do not usually demand information and (2) laboratory testing involves additional expenditure. Treating without arriving at etiological diagnosis is not evidence-based and may be unfair to the individual, who alone suffers the risk of diagnostic errors. It is also unfair to the community, since such errors and consequent wrong choice of drug(s) may contribute to the perpetuation of the pathogen in the community and to the development of drug-resistance in pathogens. Unnecessary antibiotics may also lead to drug resistance of normal flora that may be later transferred to pathogens through plasmids. Therefore, scientific medicine demands quality-assured diagnostic laboratory service. This cardinal requirement is not given due importance in many of India's public sector and private sector hospitals. Thus, laboratory surveillance is not practiced in India.
In public health, disease surveillance is to keep pathogens under scrutiny—hence pathogens must be identified in any clustering of cases. No error should be tolerated, as it may jeopardize the health of many in the community. For this reason, in most countries, the public health system maintains laboratories for use by its personnel. They are called public health laboratories, as distinct from clinical laboratories in hospitals. The district officer of public health must have access to public health laboratory. In India, there are public health laboratories, usually a few per state, mostly the continuation what the British had established during colonial era. Microbiology has advanced hugely since then but we have not kept our public health laboratories abreast with the times. In some countries, the central public health laboratory is very advanced and may act as referral laboratory for clinical laboratories in healthcare. In India, the National Centre for Disease Control (previously National Institute of Communicable Diseases) in Delhi is the foremost public health laboratory; it has all the advanced instrumentation and modern techniques for etiological determination of nearly all known pathogens.
 
THE PURPOSES OF DISEASE SURVEILLANCE
The main reason for establishing passive surveillance was (and continues to be) the early detection of any outbreak. While any one physician may see only one or two cases, collective reporting at the local or regional level will give the overall picture of an outbreak even in the beginning stage. The recognition of an outbreak is the trigger for rapid investigation and application of preventive or control measures. Surveillance of infectious diseases is thus the important link between healthcare and public health. Public health infrastructure was briefly described earlier. Public health is functionally defined as “societal actions for prevention of diseases and promotion of health”. Its effective functioning requires a public health infrastructure. In other countries, it may be called ministry of public health (distinct from ministry of healthcare 18services), Public Health Department (under ministry of health), health protection agency or public health service. The main purpose of disease surveillance is the early detection of outbreaks in order to intercept them for the present and to pre-empt them from occurring in future. The disease surveillance system of the nation can be assessed by the successes of outbreak detection and control. The reason why many outbreaks in various parts of the country are not effectively and quickly controlled is due to the lack of public health infrastructure.
Another purpose of surveillance is to monitor, quantitatively and in real-time, the degree of decline in incidence of diseases that public health system had targeted for and funds expended for prevention and control. When a government targets a disease for control, it undertakes several activities including the application of preventive interventions and their auditing requires actual measurement of disease reduction over time. The best example in India is the surveillance for polio eradication, which has been described later. Disease control is the term applied for reducing the incidence to a predetermined acceptable level through interventions. Elimination is the extreme degree of control to zero incidence in a defined population, usually a whole country. Global level elimination is eradication. For elimination the disease, surveillance has to be efficient enough to detect even one case anywhere in the country. While control may apply to disease but not necessarily the causative pathogen (as in control of neonatal tetanus) eradication must result in removal of the pathogen from human transmission in order to maintain zero incidence (as in smallpox eradication).
A third purpose of surveillance is to discover new (emerging) diseases. In passive surveillance, physicians are instructed to report not only notified diseases, but also any undiagnosed illness that may be infectious in nature and is serious enough for public health attention. A cluster of undiagnosed illness has to be reported. In 1981, physicians in California reported a few instances of death of young men with an unusual disease. They had pneumonia due to an opportunistic pathogen, Pneumocystis carinii (now renamed jerovicii) that is always associated with severe immune suppression, usually due to malignancies and their treatments. The undiagnosed condition was provisionally named “acquired immune deficiency syndrome” (AIDS)—acquired as these adults had been without any major health problems all their lives. The United States Public Health Service swung into action and by epidemiological studies identified that the common factor among them was practicing male homosexual acts. Wearing of condoms markedly reduced risk of acquiring the putative agent—unknown then and suspected to be some chemical or an infectious agent. Eventually in 1984−85, the causative virus of AIDS was discovered. Imagine, if there was no disease surveillance, or if surveillance did not attract prompt epidemiological investigations, how much time the world would have lost in detecting this emerging infectious disease and its causative agent(s). We now know that AIDS—causing severe unexplained loss of body weight and high case fatality, had been recognized by several physicians in African countries since the early 1970s and the disease even named locally (slim disease). If AIDS had first emerged in India, the situation would not have been much different. This incident illustrates the value of passive surveillance, the sincerity of physicians to diagnose pneumonia by its etiology, their alertness to conclude that the condition was new, their cooperation to report these cases and the efficiency of the public health system in investigating and unraveling the mystery. It also illustrates the importance of identifying risk factors for controlling further spread even before the agent is identified.
 
SURVEILLANCE FOR ELIMINATION OR ERADICATION
Elimination (in specified countries or cluster of neighboring countries) or eradication (globally) of diseases are examples of extreme disease control. Smallpox was eliminated in India by 1975 and so declared in 1977. Smallpox was eliminated by primary prevention with the smallpox vaccine—and by active surveillance (case-search) and vaccination of all persons who were in contact with every person with smallpox. Fortunately, smallpox did not spread widely, vaccination provided excellent protection and a fair proportion of persons in contact had been already vaccinated under the then existing practice. Immune individuals did not get infected with smallpox virus, or even if infected did not shed virus in sufficient quantity to transmit infection. Without “fever and rash” surveillance, as well as active surveillance following any rumor of fever with rash, smallpox would not have been documented to have been eradicated and eventually certified. After certification of eradication the surveillance was discontinued as the smallpox eradication staffs were reverted to their original work.
Another disease India has eliminated in the 20th century is Dracunculiasis (Guniea worm disease). In addition to human behavior modification resulting in break of the worm's transmission cycle, active surveillance was practiced in endemic geographic regions for two reasons. One was to ensure no contact between the ulcerated skin and surface water collections (to interrupt life cycle) and the second was to document its elimination.
The third major success is elimination of polio caused by natural (wild) polioviruses, as described below. Even though we speak of disease elimination or eradication, in reality what we eliminate is (in most cases) the transmission of the pathogen between humans. Therefore, in addition to clinical surveillance, every suspected case has to be investigated for the pathogen under elimination. These three examples illustrate how ad hoc and single-disease surveillance had to be established in the absence of public health surveillance. They also illustrate the non-sustainability of such efforts.19
 
PASSIVE, ACTIVE, VIROLOGICAL AND ENVIRONMENTAL SURVEILLANCE FOR POLIO ELIMINATION
In 1988, India decided to eliminate polio to join the global polio eradication initiative of the WHO. Because India used live trivalent oral polio vaccine (tOPV) under the Universal Immunization Programme (UIP), the government expected that polio would be controlled first and then eliminated by supplementary pulse immunizations. There was need to document progress toward polio elimination; hence a polio-specific passive disease surveillance system was designed and launched under a special project—the National Polio Surveillance Project (NPSP). It established reporting of acute flaccid paralysis (AFP) by all healthcare institutions where children with AFP would be taken, both in the public and private sectors—for nationwide and continuous AFP surveillance. How does NPSP assess the completeness of AFP reporting? It was known in South America that the incidence of AFP in children under 15 years of age was about 1 per 100,000 per year. The same frequency was applied in India, but soon it was found that our AFP incidence was much greater than in South America. Therefore, surveillance quality is accepted as satisfactory if every district reported annually at least two AFP cases per 100,000 children under-15 per year. In 2011, over 35,000 healthcare institutions are on the AFP reporting network: they report only AFP, no other disease.
Since polio had to be diagnosed by etiology, a network of laboratories was established, by upgrading several existing virus laboratories. They are in Kasauli, Ahmedabad, Kolkata, Lucknow, Delhi, Mumbai, Bengaluru and Chennai. The Mumbai laboratory (Enterovirus Research Centre of Indian Council of Medical Research) has been recognized by the WHO as National Reference Laboratory and as Global Specialized Laboratory, one of seven such units in the world. Stool samples were collected from every child with AFP: the aim was to get two samples from every child to increase diagnostic sensitivity. They were tested in the polio laboratories to detect polioviruses and when detected, to differentiate between vaccine viruses from natural or wild polioviruses (WPVs). This is referred to as “virological surveillance” or “active laboratory surveillance”. If laboratories passively reported the detection of agents under public health surveillance, it would supplement clinical surveillance and would qualify for “passive laboratory surveillance”. Since NPSP staff collected stool samples from all children with AFP and got them tested, the process illustrates “active laboratory surveillance”. In 2011, over 60,740 stool samples were collected and tested but only 1 WPV (type 1) was detected.
Wild polioviruses can circulate silently for short periods of time. For decades, sewage samples had been collected and tested for WPVs, by the Enterovirus Research Centre in Mumbai and WPVs were regularly detected. Since the year 2000, Mumbai sewage showed up imported WPVs with origins in Uttar Pradesh or Bihar. Sewage is equivalent to stools from hundreds of thousands of individuals. Yet, the testing sample comes from the environment. Therefore, in the context of polio, regular (usually weekly) sewage sample testing is referred to as “environmental poliovirus surveillance”. Since 2011, environmental surveillance is conducted in Mumbai, Delhi, Patna and Kolkata. In 2012, so far, all samples have proved negative, adding supportive evidence that India has eliminated WPV transmission.
 
SURVEILLANCE IN AIDS CONTROL
Acquired immune deficiency syndrome control is another success story in India. While AIDS received wide global media publicity, during the early 1980s, the government lacked a mechanism to monitor its arrival in India. Had we practiced public health surveillance, we could have expected some physicians reporting suspected cases of AIDS or at least diseases or death due to undiagnosed causes. Recognizing this deficiency, the virology department of the Christian Medical College in Vellore conducted systematic search for infection, resulting in detection of infected women in sex work in Chennai, Madurai and Vellore in February 1986. The Indian Council of Medical Research established an AIDS Task Force in mid-1986 and adopted the Vellore model of testing within hospital settings both a high-risk group (male patients in STD clinics) and a low-risk group (antenatal women) for human immunodeficiency virus (HIV) infection as the parameter for monitoring time trends of epidemiology. Thus, annual repetitive sentinel hospital-based anonymous unlinked sample surveys were established—and it got a popular name as “sentinel surveillance”. In 1986 itself, 62 “sentinel surveillance” sites were operative. Since then a number of sites have increased to over 1,000 in 2010, covering all cities and most districts in every State and Union Territory.
Today “sentinel surveillance” for HIV provides annually large samples of denominator-population and their HIV prevalence. This is the method of monitoring infection trends to date, a unique method designed in India. There is no other disease for which denominator-based infection prevalence data are available in India. Other countries did not resort to serological surveys to monitor time trends, as they had passive surveillance of cases of AIDS. However, the term sentinel surveillance is a misnomer as it is not based on principles of public health surveillance. It lacks continuity and has incomplete coverage. However, the objective is to monitor time trend, which it serves well.
 
THE STATE OF PUBLIC HEALTH SURVEILLANCE IN INDIA
During British Raj, public health surveillance was practiced in all provinces, under the Epidemics Act of 1890 and the Madras Public Health Act of 1939. Each province had established its own list of diseases for reporting. After independence the posts of Director General of Indian Medical Service, Public Health Commissioner of India and India Health Epidemiologist were abolished; thus public 20health surveillance was orphaned. The newly created post of Director General of Health Services was not assigned the responsibility of public health surveillance. As all emphasis was given to healthcare, the need for surveillance was not appreciated. However, when a disease was brought under control mode, special surveillance for that disease was established. Smallpox, Guinea Worm and polio surveillance activities were described above.
 
Malaria Surveillance
The National Malaria Control Programme was established in 1953. Two modes of surveillance were established: (1) active surveillance where malaria was hyperendemic and (2) passive surveillance everywhere else. Since passive surveillance was not enforced for any disease, malaria surveillance also fell by the wayside. For active surveillance, a worker visits every household once in 2 weeks, and blood smear is collected from anyone who had fever during the interval—smears are examined for malarial parasites. Using the data, the following indices are derived: slide positivity rate; slide falciparum rate; annual parasite incidence; annual blood examination rate; annual falciparum incidence.
 
Leprosy Surveillance
The National Leprosy Control Programme was established in 1955. Leprosy-specific diagnosis and treatment centers were established at key locations. The leprosy workers conducted periodic population surveys (active surveillance) for clinical evidence of leprosy—thus annual prevalence rate was calculated. After the goal of leprosy elimination was declared occasional mass surveys were conducted—and continues even now. The aim is to keep the new case detection at less than 1 per 10,000 population, which is used to define “elimination”. However, epidemiologically this is not true elimination—which is zero incidence in the defined geographic community.
 
Other Diseases under Control Mode
The Union Ministry of Health has targeted a few other diseases for control, namely tuberculosis (TB), lymphatic filariasis, kala azar, dengue, chikungunya fever and Japanese encephalitis (the last five under National Vector-borne Diseases Control). Neither passive nor active surveillance is practiced for them and the status of control remains not properly monitored. In May 2012, the ministry of health has notified pulmonary TB as reportable. However, the modalities of reporting, data receiving agency, follow-up and actions following case reporting have not yet been clearly described. The present requirement is for reporting sputum smear-positive pulmonary TB; other forms including pediatric TB are not yet demanded for reporting.
 
Expanded Program on Immunization
The National Childhood and Antenatal Immunization Programme, launched in India in 1978–79, has been renamed the Universal Immunization Programme (UIP). Although the objective is to prevent vaccine-preventable diseases in individuals and control their incidence in the community, systematic surveillance of targeted diseases was not established. The numbers of cases reported through the hierarchy of government healthcare units are received and compiled by the union ministry of health; however, neither the sensitivity (what proportion of total cases was captured) nor specificity of case diagnosis (what proportion of cases had accurate diagnosis) is checked for validation. Countries practicing public health surveillance did not have to establish a polio-specific surveillance method, but India had to establish NPSP. Now measles is getting targeted for mortality elimination, followed by disease elimination itself. The responsibility for measles surveillance, including laboratory verification of outbreaks, has been entrusted with the NPSP. The network of polio laboratories have been equipped for measles diagnosis and supplied with the necessary reagents. The NPSP measles outbreak monitoring and laboratory confirmation project was begun in 2006 in Andhra Pradesh, Tamil Nadu and Karnataka; in 2007 Kerala, West Bengal and Gujarat were added; during 2009−2011 Rajasthan, Madhya Pradesh, Assam, Bihar and Chhattisgarh were added. When investigated, many outbreaks clinically named measles turned out to be rubella. Consequently, the UIP is getting ready to include rubella vaccination in India.
 
INTEGRATED DISEASE SURVEILLANCE PROJECT
The concept of integrated disease surveillance is to link together all existing ad hoc or single disease surveillance activities under one umbrella. Two models of integrated surveillance have been developed in India. In 1994, there was an outbreak of suspected pneumonic plague in Surat city. An expert committee examined the reasons why such an outbreak occurred and how the nation should prepare itself for any future outbreaks of emerging or re-emerging infectious diseases. It recommended the replication of a model established in one district in Tamil Nadu and all districts in Kerala for “district level disease surveillance” (DLDS) in which private sector and public sector physicians or pediatricians reported 15 notified diseases using a preformatted and postpaid post-card. Its advantages included low cost, immediate local action to prevent or control the spread of any outbreak. Feedback to reporting physicians was through a monthly bulletin which provided information on frequency of diseases, outbreaks and actions taken against them. This decentralized district-based system (with the afferent and efferent limbs and central processing unit within the district) was not aligned with the national policy that disease control and outbreak investigations belonged to the Union Government, while only healthcare and training or education of healthcare personnel belonged to State Governments. This tension led to the establishment of centrally sponsored and 21funded data collection mode named Integrated Disease Surveillance Project (IDSP).
Integrated Disease Surveillance Project was launched in November 2004 to detect disease outbreaks quickly. The Central Surveillance Unit is at National Center for Disease Control (NCDC), Delhi. Until 2012, it was in project mode, but currently it is nested within the National Rural Health Mission. Weekly reports are generated from primary care units (subcenters, primary health centers, community health centers) which were earlier reporting disease statistics using a format different from that supplied by IDSP. Hospitals in public and private sectors are also in the network, but their involvement is incomplete. Instead of case-reporting as in public health surveillance, disease reporting in IDSP is cumbersome—lengthy forms are to be filled in for “syndromic” diagnosis, probable cases and laboratory data. Electronic reporting is encouraged. Here “integration” is not linking all ongoing surveillance activities, but a new concept—combining reporting of non-communicable diseases along with infectious diseases. Thus, IDSP in India is yet another vertical project as the afferent and efferent limbs touch one central agency—the NCDC. It does not encompass the definitional requirements of public health surveillance. Private sector could not be linked as in the case of DLDS.
The weakness of IDSP is that it has not filled the gaps in disease surveillance for those diseases that are already targeted for control, namely vaccine-preventable disease, TB, malaria and several others discussed above. As the need arose for surveillance of outbreaks of acute neurological diseases (meningococcal meningitis, Japanese encephalitis and those of unknown etiology) and of pneumonias, rotavirus gastroenteritis, etc. more surveillance projects had to be launched as described below.
 
SENTINEL-BASED SURVEILLANCE OF SELECTED DISEASES
 
Influenza Sentinel Surveillance
The National Institute of Virology has been investigating influenza—epidemiology and viral strain identification—for a few decades. However, nationally influenza had not received much attention. In 2004, a multicenter influenza monitoring laboratory network was established: the sites are at Pune, Delhi, Kolkata and Chennai. After the 2009, pandemic influenza reached India; the network was expanded to more centers including Vellore, Mumbai and Lucknow. The information collected in these laboratories is submitted to the WHO.
 
Rotavirus Sentinel Surveillance
A network of four laboratories have been assigned the task of identifying and typing rotavirus isolates from ten sentinel hospitals in six States, namely Tamil Nadu, Maharashtra, Madhya Pradesh, West Bengal, Assam and Delhi. Under-5 children with acute gastroenteritis requiring rehydration will be monitored and their stool samples submitted to the designated laboratories (Vellore, Pune, Mumbai, Kolkata).
 
Invasive Pneumococcal, Haemophilus influenzae and Meningococcal Disease Surveillance
The Indian Council of Medical Research in collaboration with NCDC is in the process of developing 30 sentinel sites to develop data base to monitor the burden of invasive bacterial diseases due to pneumococci, meningococci and Haemophilus influenzae type b. Since vaccines are available against these diseases baseline data are important to help policy decisions on the use of these vaccines. Once vaccines are introduced, the assessment of vaccine effectiveness requires surveillance data. When pneumococcal vaccine is introduced, serotype prevalence needs to be monitored in case new serotypes replace vaccine serotypes.
 
Encephalitis Sentinel Surveillance
The Indian Council of Medical Research (ICMR), with the help of NPSP is in the process of developing sentinel surveillance in several districts where Japanese Encephalitis is prevalent. These sites will help in monitoring vaccine effectiveness.
 
CONCLUSION
If a government wants to control infectious diseases, the first step is to establish surveillance. All diseases targeted for control must be covered in surveillance. Since disease-control activities require a functional Public Health Department, the process of disease surveillance is best conducted by the local (district and city) public health officer and staff. Routine passive surveillance is, therefore, called “public health surveillance”. In India, there is no unified public health surveillance, but instead there are several vertical, but nationwide disease monitoring programs including case-based surveillance for AFP, outbreak monitoring of measles and rubella, IDSP and several sentinel surveillance projects. Ideally integrated surveillance should replace all fragmentary disease monitoring projects, but unfortunately it is not possible under the present circumstances in which healthcare is under State Governments but disease prevention and outbreak control are under the Union Government. A practical redesign of Union–State relationship will help the creation of a truly integrated public health surveillance for all diseases of public health importance.
 
BIBLIOGRAPHY
  1. Government of India, Ministry of Health and Family Welfare. Integrtaed Disease Surveillance. [online] Avaialble from http://www.idsp.nic.in/ and http://www.mohfw.nic.in/NRHM/PIP_09_10/Delhi/IDSP_text.pdf.
 
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1.3 ROLE OF GAVI IN THE CONTROL OF VACCINE-PREVENTABLE DISEASES IN INDIA
Naveen Thacker, Ashish Pathak
 
INTRODUCTION
Global Alliance for Vaccines and Immunization (GAVI, the Vaccine Alliance) is an international organization, which was created as a public–private partnership and is committed towards increasing access to immunization in poor countries. GAVI brings together United Nations Children's Fund (UNICEF), the World Bank, the vaccine manufactuers from resource-rich and resource-poor countries, donors from the resource-rich countries, and representatives from governments of the low-income countries across the world and Civil Society Organizations (CSOs).1
Since its inception in 2000, GAVI's support has contributed to the immunization of an additional 500 million children in low-income countries and has averted 7 million deaths due to vaccine-preventable diseases. GAVI has supported more than 200 vaccine introductions and campaigns in low-income countries during the 2011–2015 period between 2016 and 2020, GAVI will help countries to immunize another 300 million children against potentially fatal diseases, saving between 5 and 6 million lives in the long term.2
The mission of GAVI is “saving children's lives and protecting people's health by increasing equitable use of vaccines in lower-income countries”.3
 
HOW DOES GAVI WORK?
GAVI invites applications for support from governments of those countries whose gross national income per capita is below GAVI's eligibility threshold, this threshold was US dollar 1580 in the year 2015. Based on the eligibility threshold, 73 countries are eligible for GAVI support. GAVI purchases vaccines through UNICEF, and provides them to governments whose applications are approved.1
 
GAVI'S STRATEGY
GAVI's strategy is a roadmap designed to help it respond to changes in the vaccine landscape and set five-year milestones en route to fulfilling its mission.4 The 2016-2020 strategy is the latest in four distinct phases since GAVI's inception:
Phase IV (2016–2020)
Phase III (2011–2015)
Phase II (2007–2010)
Phase I (2000–2006)
Phase IV (2016–2020)
This section details the strategic objectives and operating principles for the current phase (2016–2020) as well as providing an overview of previous strategies.
The 2016–2020 strategy has four goals, each supporting GAVI's overall mission:5
  1. The vaccine goal: Accelerate equitable uptake and coverage of vaccines.
  2. The systems goal: Increase effectiveness and efficiency of immunization delivery as an integrated part of strengthened health systems.
  3. The sustainability goal: Improve sustainability of national immunization programmes.
  4. The market-shaping goal: Shape markets for vaccines and other immunization products.
 
PRINCIPLES
The GAVI's strategic framework includes eight principles, intended to define the Vaccine Alliance's characteristics, its business model and its aspirations, these are: country-led, community-owned, globally engaged, catalytic and sustainable, integrated, innovative, collaborative and accountable.4
 
GAVI'S HEALTH SYSTEM STRENGTHENING GRANTS
GAVI is dependent on the effectiveness of the countries health system to deliver life-saving vaccines, thus GAVI supports countries to strengthen country health system by proving health system strengthening (HSS) grants.1 The strategic objectives under the health systems goal are to:
  1. Contribute to resolving the major constraints to delivering immunization.
  2. Increase equity in access to services
  3. Strengthen civil society engagement in the health sector.
 
GAVI'S ESTIMATED IMPACT IN 2016–2020 PERIOD
The estimated impact of GAVI in its next phase can be measured by number of children that would be saved from vaccine-preventable diseases per country and thus, globally. In the 2016–2020 period, India will contribute to largest number of deaths averted globally (Fig. 1.3.1).
 
GAVI'S SUPPORT TO INDIA
India has always been special for GAVI. India is the largest and most populous GAVI-eligible country with a birth-cohort of almost 27 million.23
zoom view
Fig. 1.3.1: Countries that will contribute to highest percentage of deaths averted through vaccine-preventable diseases through GAVI support in the period 2016–20206.
Also, India still accounts for one-fifth of child deaths worldwide and more than a quarter of all under-immunized children in GAVI-eligible countries (please look at Figure 1.3.2 for details). India remains eligible for GAVI support based on its GNI level. But because of the large birth cohort of India, GAVI has limited its support to catalytic funding to India. Until 2011, there was a limit placed on GAVI support to India, which was removed with the condition that the GAVI Board continues to review any new support case-by-case.7
 
IPV Introduction Support
The National Technical Advisory Group on Immunization (NTAGI), the apex body for decision making on immunization related issues in India, recommended a comprehensive IPV introduction plan to the Government of India (GoI).8 India applied for funding to GAVI in September 2014, for the period of September 2015 to 2018 at an estimated cost of US dollar 160 million. In November 2015, India launched IPV in six states and has expanded it to all states and Union Territories.6
 
HEALTH SYSTEM STRENGTHENING SUPPORT TO INDIA
As part of HSS initiative, GAVI has disbursed US dollar 30.6 million for the IPV introduction and US dollar 107 million in the year 2014–2015 to India.1 The grant has been focused by GoI for use in 12 states and 127 underperforming districts and is synergistic to Mission Indradhanush.10 Specifically, the grant has been used to strengthen the cold chain management. To enhance human resource capacity, national cold chain vaccine management resource center has been established in New Delhi. National cold chain training center has been strengthened in Pune. In 20 districts across UP, MP and Rajasthan, electronic vaccine intelligence network (eVIN) has been implemented to enable real time information on cold chain temperatures, vaccine stocks and flows. To increase demand for routine vaccination, National Behavioral Change and Communication (BCC) strategy has been developed and immunization messages have been developed and broadcast through mass media. The national monitoring and evaluation plan for immunization has been drafted and monitoring and evaluation of routine immunization is currently functional in 24 of the 36 states and UTs across India. Two rounds of survey for National Immunization Coverage Evaluation have been done in 2015. This evaluation will further identify low-performing districts for routine immunization coverage. Guidelines for tagging high-risk low-coverage areas have been developed along with WHO India National Polio Surveillance Program (NPSP).1
zoom view
Fig. 1.3.2: Number of under-immunized children 2014 (in millions).
 
Targeted Country Assistance for India for 2017
GAVI works through its incountry partners in India. They are WHO, UNICEF and the CDC. In 2017, UNICEF through GAVI support will support a) the implementation and national monitoring of Mission Indradhanush, with a focus on 12 low-performing states. The expected outcome is that improvements in immunization coverage are inclusive of the children in the most marginalized, remote and poorest communities and overall inequities within the immunization program are reduced. UNICEF will also support planning, preparedness assessment and roll out of pneumococcal and rotavirus vaccine in identified states, will support the implementation of a high-quality MR state campaigns, with a focus on social mobilization, cold-chain performance and real time monitoring and will support national electronic vial monitoring assessments. The WHO through GAVI support will address immunization equity in states with low-immunization coverage with focus on North-Eastern states. CDC, Atlanta through GAVI support will provide technical assistance to the National Institute of Cholera and Enteric Diseases (NICED), the state of West Bengal, and the Central Ministry of Health to understand the disease and economic burden of cholera in the State of West Bengal.24
 
Impact of GAVI Initiatives in India
GAVI has been providing assistance to the Government of India since 2002. Over the past decade, India has received support in three areas:
 
a. Hepatitis B Monovalent Vaccine
GAVI, through its New Vaccine Support (NVS) grant, helped India to introduce the hepatitis B monovalent vaccine. Support began in 2002 with a vaccine introduction grant for $100,000. For 6 years, from 2003 to 2009 and excluding 2004, a total of $26,486,033 was disbursed for Hep B mono vaccine; funding was used to purchase the vaccine and injection supplies with the Government of India funding other immunization support.11
In 2002, hepatitis B was introduced in 33 districts and 10 cities in India with GAVI Phase I support. In 2007–2008, coverage was expanded to 10 states with GAVI Phase II support. In 2010, the Government of India took over funding for Hep B immunization in the 10 states, and in 2011 introduced the vaccine nationwide with its own funding.11
Final impact: Universal introduction of hepatitis B vaccine with Government of India supporting 100% immunization.
 
b. Injection Safety Support
Injection Safety Support (INS) grant helped India to introduce autodisable syringes in its immunization program. Two grants were given in 2005 and 2007 and a total of US$ 18,427,489 was disbursed.
Final impact: Autodisable syringes have become the standard for all routine Expanded Programme on Immunization (EPI), and a national policy for safe disposal of injection waste has been developed. The Government of India is now funding the purchase of auto-disable syringes 100%.11
 
c. Pentavalent (DTP-HepB-Hib) Vaccine Support
New vaccine support (NVS) to introduce pentavalent DTP-HepB-Hib (Penta) vaccine.
India's NTAGI recommended the introduction of Penta in 2008. GAVI support began in 2008 with a vaccine introduction grant for US$ 1,100,000, although 70% of this was returned when India decided on a phased introduction in 2011 instead of a nationwide introduction as was originally planned. US$ 443,500 of the grant was used to support the phased introduction. In December 2011, India introduced Penta in two states (Keral and Tamil Nadu) with GAVI support. Six additional states introducted in 2012.12
Final impact: Currently, all states have introduced Penta in routine immunization in India. India received a total of US $266,711,053 as of 23rd August, 2017, to support the introduction of Penta.12
 
IMMUNIZATION IN INDIA AND GAVI'S CRITICAL ROLE IN ACCELERATING GREATER ACHIEVEMENTS OF HEALTH IMPACT
With a birth cohort of 27 million children born each year, India accounts for one third of children born in GAVI-eligible countries. While India has made substantial progress in reducing the number of under-five deaths, it is still the highest in the world (1.3 million in 2013, 20% of the global total). The gravity of the problem varies significantly among states and areas of residence. Vaccine-preventable diseases are a key cause of mortality and morbidity. India has ~20% of pneumococcal, rotavirus and measles deaths worldwide, 25% of cervical cancer deaths, and 38% of the global congenital rubella syndrome (CRS) burden in terms of cases. Under India's Universal Immunisation Programme, vaccination is currently provided to prevent DTP (diphtheria, pertussis, tetanus), polio, measles, severe forms of childhood tuberculosis, hepatitis B (Hep B), Haemophilus influenzae type B (Hib) infections, and Japanese Encephalitis (in selected districts). GAVI provided catalytic support to accelerate the introduction of Hep B, pentavalent and inactivated polio (IPV) vaccines, as well as safe injection devices (INS) and on health systems strengthening. Under an exemption to the Alliance's co-financing policy, GAVI provides time-bound support and the government pays for introduction costs and related immunization commodities, taking on full self-financing for vaccines or devices after GAVI support ends (Fig. 1.3.3).6
The recent years have marked a turning point for the UIP. India's polio-free certification in 2014 and its elimination of maternal and neonatal tetanus in 2015 are landmark achievements. The political environment for immunization is also particularly strong now. In December 2014, the government launched the world's largest immunization drive, “Mission Indradhanush”, aimed at increasing immunization coverage to more than 90% by 2020 by targeting districts that have the most unvaccinated or partially vaccinated children. Initial results are encouraging: 2 million children were fully immunized in the first four rounds of the mission. Mission Indradhanush builds on new approaches that are implemented through GAVI's catalytic HSS grant. The US$ 107 million grant focuses on 12 underperforming states. An innovative pilot electronic information system to manage vaccine logistics is being scaled up in three states. Regular supportive supervision of cold chain points has been initiated at primary care level, and state-level communication plans have been created. The experience and expertise gained in the vast polio infrastructure is being applied to routine immunization, contributing to India's goal of universal coverage.625
zoom view
Fig. 1.3.3: GAVI support to India to date, with programs sustained/to be sustained by the Government of India (US$ millions).6
A strengthened partnership in the coming years offers considerable benefits for both India and GAVI. GAVI's vision is that between 2016 and 2021, GAVI's targeted support will accelerate India's efforts to introduce new vaccines and achieve universal immunization coverage. Millions more children will be immunized by several vaccines in GAVI's portfolio, increasing the number of future deaths averted with GAVI support by at least half a million. India will reach a position where it can sustain a self-financed, multi-faceted and equitable immunization program. GAVI and India will both benefit by capitalizing on procurement savings and enhancing vaccine supply security, while forging a collaborative, learning-based relationship. To realize this vision, GAVI proposed a comprehensive, multi-pronged strategic alliance partnership with India. The strategy builds on the principles endorsed by the programme and policy committee (PPC), it takes India's priorities and GAVI's added value into consideration, and envisages timebound, catalytic support:
  1. Increase immunization coverage and equity in India through targeted support to strengthen the routine immunization system.
  2. Maximize health impact by accelerating adoption of new vaccines in India.
  3. Maximize procurement savings and vaccine supply security by sharing information, coordinating tactics and building a long-term strategy that strengthens local, public and private sector manufacturers.
  4. Ensure that vaccine programs in India will be sustainable beyond 2021 by supporting the government to plan for the transition and advocating for increased domestic spending on immunization.
 
The Coverage and Equity Opportunity
Though the UIP has been operating for more than 30 years, only 65% of children receive all vaccines during their first year. While WHO/UNICEF coverage estimates for India were revised upward this year (from 72% to 83% DTP3 coverage), India is still the country with the largest number of un- or under-vaccinated children in the world, at 4.1 million in 2014 (Fig. 1.3.1). Vaccination coverage varies significantly among geographies (Fig. 1.3.4). Some of India's states are among the largest and poorest in GAVI's portfolio. Uttar Pradesh, for example, is larger than every GAVI-eligible country except Nigeria, has gross national income per capita of only US $422, and has a DTP3 coverage of only ~60%. Coverage also varies depending on gender, area of residence, wealth and caste. Operational challenges in demand generation, cold chain and logistics management, and other areas hinder progress.
Alliance partners have work with the Government of India to develop a detailed proposal with targets and indicators and ensure that future GAVI support further addresses coverage inequity issues in the country. Cold chain and logistics management, demand generation and vaccine-preventable diseases (VPD) surveillance are some potential new areas within which GAVI is looking forward to invest.6
 
THE NEW VACCINES OPPORTUNITY
With the positive political environment, India has an ambition to eliminate measles, introduce rubella (as part of MR vaccine), rotavirus, and pneumococcal vaccines in 2016–2017, and potentially HPV vaccine at a later time during the transition period.26
zoom view
Fig. 1.3.4: Percent of fully immunized children (FIC) in large Indian states.6
Rollouts of these vaccines are at different stages of planning given the status of recommendations from the National Technical Advisory Group on Immunisation (NTAGI) and political approvals for each vaccine. GAVI support will play an important role in accelerating roll-out of new vaccines, which would be critical to argue for allocation of more domestic resources in the next national Five-Year Plan and cMYP (2018–2022).
 
THE MARKET-SHAPING OPPORTUNITY
The strategic partnership between GAVI and the Government of India offers opportunities to optimize both short- and long-term vaccine supply security, to capture procurement cost-savings based on the increased demand, and to share information and best practices on managing vaccine markets effectively. Each vaccine market will require a specific approach. The markets with the greatest opportunities today for procurement savings are pentavalent and pneumococcal. While other markets, such as IPV, MR and rotavirus, have limited scope for procurement cost-savings, these markets will require close coordination with regard to supply. Building a strong local base of private and public vaccines and cold chain equipment that complements the global availability will be beneficial across the whole portfolio. Benefits of a well- executed partnership will extend beyond GAVI and India to include low income countries that are dependent on a reliable supply of low-cost and high-quality vaccines and cold-chain equipment.3
 
ENSURING SUSTAINABLE PROGRAMMING
GAVI engagement in the form of senior leadership advocacy and support via communication and advocacy agencies have resulted in evidence-based policy discussions at both the national and state levels and have achieved a higher prioritization for health issues. Alliance advocacy for political commitment to increase health spending, including immunization, is paramount. A Political Forum on Child Health and Survival which includes selected Members of Parliament was recently formed in 2012. This new structure serves as a forum for political and public discourse around the need for high-quality, cost-effective public health interventions, including vaccines.
India has a successful track record in continuing the Hep B and INS programs with its domestic resources after GAVI support ended. The government has also indicated in writing to the GAVI Secretariat its commitment to sustain and further scale up rotavirus, pneumococcal and HPV programs and self-finance MR routine immunization after future catalytic support ends. However, given the magnitude of increase in resources expected with the launch of new vaccines (two to ten-fold increase by 2021 from the current ~US$ 40 million per year on vaccine costs only 25), GAVI engagement with India to ensure successful transitioning is critical.627
 
THE IMPORTANCE OF INDIA AS A MANUFACTURING BASE FOR VACCINE AND COLD CHAIN EQUIPMENT
Vaccine manufacturers in India are a key source of supply for GAVI. In 2014, they provided nearly 60% of vaccine volume, representing just over 30% of the total value of procurement. A single Indian manufacturer supplied 100% of measles-rubella (MR) and meningococcal A (MenA) conjugate vaccines and 80% of measles vaccine, while four manufacturers supplied over 80% of pentavalent vaccine.6 Vaccine demand in India could reach nearly 30% of total demand in the 73 GAVI countries. The resulting significant increase in market volumes presents both risk and opportunity. It could disrupt supply of important vaccines if coordination is insufficient. If the increase is managed well, however, it will allow optimization of production costs and procurement savings.6
 
REFERENCES
  1. Thacker N, Thacker D, Pathak A. Role of Global Alliance for Vaccines and Immunization (GAVI) in Accelerating Inactivated Polio Vaccine Introduction. Indian Pediatr. 2016;53(Suppl 1):S57–S60. PubMed PMID: 27771641.
  1. GAVI 2016. Every Child Counts: The Vaccine Alliance Progress Report 2014. Available from http://www.gavi.org/progress-report/. Accessed September 11, 2017 http://www.gavi.org/results/gavi-progress-reports/
  1. GAVI's strategy, Mission 2016–2020 http://www.gavi.org/about/strategy/ Accessed September 11, 2017.
  1. GAVI, the Vaccine Alliance 2016-2020 Strategy http://www.gavi.org/library/publications/gavi/gavi-the-vaccine-alliance-2016-2020-strategy/ Accessed September 11, 2017.
  1. GAVI's strategy, phase IV (2016-20) - GAVI, the Vaccine Alliance http://www.gavi.org/about/strategy/phase-iv-2016-20/ Accessed September 11, 2017.
  1. Szeto C, Malhame M, Gehl D, et al. Report to the Board 2-3 December 2015 Alliance Partnership Strategy with India, 2016-2021.
  1. GAVI 2015. Alliance Partnership Strategy with India, 2016-2021 Report to the Board 3rd December 2015. Available from http://www.gavi.org/Library/News/Press-releases/2016/Historic-partnership-between-GAVI-and-India-to-save-millions-of-lives/. Accessed September 11, 2017.
  1. India's National Technical Advisory Group on Immunisation T. Jacob John. National Technical Advisory Group on Immunisation,  New Delhi, India www.nitag-resource.org/…/01/6706ca25a105266e834edb78f7f81cec124420ec.pdf
  1. Joint Appraisal Report India, 2015, Available from http://www.gavi.org/country/india/documents/#approvedproposal. Accessed September 11, 2017.
  1. Mission Indradhanush http://www.missionindradhanush.in/about.html Accessed September 11, 2017.
  1. Parthasarathy A. Textbook of Pediatric Infectious Diseases. 2013; New Delhi: Jaypee Brothers Medical Publishers. 
  1. Pentavalent vaccine support http://www.gavi.org/support/nvs/pentavalent/ Accessed September 11, 2017.
 
28
1.4 RATIONAL DRUG THERAPY IN PEDIATRIC INFECTIOUS DISEASES
YK Amdekar
 
INTRODUCTION
Rational drug therapy means “prescribing right drug for right indication, in adequate dose for optimum duration that delivers safe and appropriate benefit to the clinical needs of the patient at lowest cost”. The concept of rational drug therapy is age-old, as evident by the statement made by the Alexandrian physician Herophilus, 300 BC that states “Medicines are nothing in themselves but are the very hands of God if employed with reason and prudence”. The physician should always bear in mind that drugs do not cure. They may be made valuable adjuncts in our endeavor to restore normal function in an abnormal functioning organ. Improving precision and economy in prescribing drugs is a goal whose importance has much more increased with proliferation of new and potent agents and with growing economic pressures to contain health- care cost.
 
GENERAL PRINCIPLES OF RATIONAL DRUG SELECTION
 
Right Indication
Selected drug must be relevant to treatment of concerned disease. Such a drug could be either specific curative drug such as antibiotic or merely a symptomatic reliever. Specific drug therapy is possible only when there exists at least a provisional diagnosis as in case of use of antibiotic for infection. Symptomatic reliever must be used only when symptoms cause a reasonable discomfort to a child. For example, antipyretic should not be used just because of presence of fever. It should be used only if fever is high enough to make a child uncomfortable or pose danger to life as in case of hyperpyrexia. Thus, symptomatic reliever should be used as per the need (on SOS basis) and not on predetermined fixed schedule. It is also true about symptomatic therapy for cough or diarrhea. In fact, there is no cough remedy that “cures” cough. At best, it may relieve discomfort of coughing. Hence, bronchodilator or cough suppressant may be used with caution. It is now well accepted that there is no need for symptomatic control of diarrhea. Besides, stool-binding agents are harmful probiotics are not routinely indicated in diarrhea. Zinc supplement in diarrhea is rational, especially in malnourished children.
 
Efficacy and Safety
These are most important parameters of rationality. Safety is as much to be ensured as efficacy, more so in case of long-term therapy. It is true that every drug is likely to cause side effects and so, every attempt must be made to use non-pharmacological therapy whenever available, before prescribing a drug. For example, good ventilation, optimum room temperature and light clothing help to control fever. Similarly, hydration and propped up position help to relieve cough. Maintaining good nutrition and hydration is key to treatment of diarrhea. Control of trigger factors in treatment of asthma is vital to therapeutic success. Such measures often obviate need for a drug or can do with minimum drugs.
 
Risk–Benefit Ratio
It is rational to evaluate probable outcome of using or not using a drug. One must compare risk and benefit of administering the drug as well as withholding the drug. Similarly, one must choose the best drug with favorable risk–benefit ratio.
 
Cost
Cost is the concern to less privileged society but even to the affordable population. If alternate drug is cheap, one must not hesitate to use it. It is not true that generic drugs are inferior to branded drugs.
 
Quality
Unfortunately, there is no way for a doctor to assess quality of the drug. It is personal experience that dictates using a drug manufactured by a particular company. Quality of a drug is to be taken for granted although one must keep in mind the possibility of spurious drugs. Past record of the manufacturer and personal experience of a drug helps to decide the quality.
 
Appropriateness
Rationality cannot be considered to be fixed or rigid endpoint of drug therapy in all situations. Cotrimoxazole is a rational choice for the treatment of acute respiratory infection (ARI) in ARI control program in the community because it is cheap, safe, oral, fairly effective and available in simple dosage formulations. But, it is not necessarily the best choice for individual child as specific antibiotic can be considered better, depending upon probable bacteriological diagnosis. Appropriateness should also be decided by capability and competence of local physician to make correct diagnosis and monitor proper therapy. For example, intravenous therapy may be ideal for acute 29bacterial infection in an infant but may not be feasible due to physician's inability to administer intravenous drug and so intramuscular route may be an alternative, although inferior. Single dose of intramuscular injection of benzathine penicillin or aminoglycoside has been used in specific conditions.
 
Single Ingredient Drug
Fixed dose combination drugs are best avoided in routine practice, except in specific situations such as cotrimoxazole, anti-tuberculosis drugs or antibiotic with enzyme inhibitor. If two drugs are necessary for treatment, as in case of neonatal sepsis, they are best administered separately so that individual dosage and duration can be suitably adjusted. There are many irrational combinations in the market such as combination of quinolone and metronidazole for mixed gastrointestinal (GI) infection. Such mixed infection is rare in children.
 
RATIONAL ANTIBIOTIC THERAPY
Infections are common in children and fever is a common presentation. Fever does not equate with infection and not necessarily bacterial infection that may justify an antibiotic. After all, viral infections are common in the community and should not be treated with an antibiotic. Further, not all bacterial infections deserve an antibiotic prescription. However, antibiotics are prescribed for majority of children presenting with fever. In fact, they may also be prescribed for children who have no infection as in case of cough due to hyper-reactive airway disease. Thus, antibiotics are often prescribed without proper diagnosis for fear of probable bacterial infection and antibiotics are often changed or multiple antibiotics used due to fear of worsening condition. Misuse of antibiotics in this way leads to increasing drug resistance which has become a major concern today. Besides, irrational use of antibiotic may suppress but not control infection that would pose difficulty in diagnosis with increased morbidity and risk of mortality. Thus, improper antibiotic use is a threat to the community and also to an individual patient. If this trend continues, it may not be long before even a simple infection may not be amenable to drug therapy.
 
WHEN SHOULD AN ANTIBIOTIC BE PRESCRIBED?
 
Attempt a Bacteriological Diagnosis
Antibiotic is indicated only in case of bacterial infection. It is ideal to attempt bacteriological diagnosis in every child with suspected bacterial infection, although it is not practical in routine office practice. However, few conditions demand proof of bacterial infection as in case of urinary tract infection (UTI) and typhoid fever. Urinary tract infection in children is potentially a serious disease with a risk of permanent renal damage if not properly diagnosed and treated. Typhoid fever being a bacteremic infection, blood culture is often positive and technically, it is easy to culture Salmonella typhi. It is, therefore, expected that UTI and typhoid fever are bacteriologically diagnosed as often as possible and empirical treatment is not justified. Gastric lavage for acid-fast bacilli should be tried in the diagnosis of childhood tuberculosis. Throat swab for streptococcal infection is a routine in western countries. In case culture facilities are not available, at least, circumstantial evidence should be collected before embarking on specific antibiotic therapy.
 
CIRCUMSTANTIAL EVIDENCE OF BACTERIAL INFECTION
Typical clinical syndrome in an acutely febrile child may strongly suggest bacterial infection that may not need further proof for rational antibiotic prescription. Acute tonsillitis is clinically diagnosed by finding beads of pus on inflamed tonsils and tender submandibular lymph nodes. Loose stools with blood and mucus and abdominal cramps suggest acute bacillary dysentery. Localized chest findings in an acutely febrile child who develops tachypnea denotes bacterial pneumonia that may be confirmed by chest X-ray but even without chest X-ray would justify antibiotic therapy.
Laboratory evidence of bacterial infection should not be considered in isolation without clinical correlation. Neutrophilic leukocytosis and high C-reactive protein may favor bacterial infection but not adequate enough by themselves to consider antibiotic therapy. Bacteremic bacterial infections start with moderate degree of fever that becomes more severe by day 3−4 as happens typically in typhoid fever. However, bacterial infections localizing at the site of entry such as tonsillitis or UTI may start with high degree of fever.
 
WHEN THERE IS NO CLUE TO DIAGNOSIS
This is the most common situation in routine office practice during first few days of onset of fever. Generally, one can arrive at a reasonably correct diagnosis only after disease evolves over few days after onset of symptoms. It means that correct diagnosis is often not possible in a febrile child in first few days with exception sited above such as tonsillitis and bacillary dysentery. At such stage, it is important to assess risk of waiting without specific antibiotic in an acutely febrile child.
Following situations in acutely febrile child are considered to be at risk of serious bacterial infection that demands urgent specific action:
  • Age less than 3 months
  • Severe protein–energy malnutrition30
  • Immunosuppressed state
  • Behavior abnormality—lethargy or extreme irritability
  • Tachycardia and tachypnea disproportionate to degree of fever.
In such situations, laboratory tests should be ordered before starting empirical antibiotic and decision taken for need for hospitalization. Laboratory tests may be prioritized on individual merits and they include complete blood cell, urinalysis, chest X-ray, blood and urine culture and cerebrospinal fluid examination.
 
WHEN THERE IS NO CLUE TO DIAGNOSIS BUT IS SAFE TO WAIT
In absence of risk factors in a febrile child, it is rational to wait and observe progress without antibiotic therapy. Fever should be controlled with paracetamol. Parents must be counseled about danger symptoms such as behavioral abnormality and reduced urine output that demand reporting to medical facility. Periodic clinical examination is necessary over next few days to pick up clinical clues to diagnosis. Attempt must be made to differentiate acute bacterial infection from acute viral infection. It is possible to a reasonable extent by detailed analysis of history of fever (Table 1.4.1).
 
PRINCIPLE OF CHOOSING AN ANTIBIOTIC
Once need for an antibiotic is rationally decided, next step is to choose right antibiotic. Choice of antibiotic should depend upon several factors.
 
Site of Disease
Disease above the diaphragm is generally caused by Gram-positive cocci and is treated with penicillin, macrolide, first-generation cephalosporin. Disease below diaphragm is mostly caused by Gram-negative bacilli and is treated with aminoglycoside, third-generation cephalosporin or quinolone.
Table 1.4.1   Clue to probable cause of acute infection
Bacterial
Viral
Malaria
Degree at onset
Moderate
High
High
Rhythm
Regular
Regular
Irregular
Response to paracetamol
Poor
Fair
Erratic
Interfebrile state
Sick
Normal
Normal
Progress on day 3–4
Persisting
Better
Variable
Contact history
None
Positive
None
Extent of disease
Localized
Generalized
 
Epidemiological Data
Antibiotic should be selected on the basis of local epidemiological data regarding drug sensitivity pattern. It may be variable in different regions and even in the same region in different institutes. It is ideal to monitor periodical changes that may occur in drug sensitivity pattern. This is important especially in critical care units wherein resistant strains may develop easily.
 
Source of Infection
Community-acquired infection is likely to be sensitive to first line of antibiotics, while nosocomial infection is often antibiotic resistant.
 
Type of Disease
Choice of antibiotic differs depending upon factors such as localized or generalized, superficial or deep, acute or chronic, mild or severe, extracellular or intracellular disease.
 
Drug Factors
It is always ideal to enquire about history of allergy to drugs. Drug interactions are best avoided by using as minimum number of drugs as possible. One must also keep in mind adverse effects of drugs and communicate effectively with parents so that timely action is taken.
 
Previous Exposure to Antibiotics
It is likely that organisms may have become resistant to previously used antibiotics in recent past. Hence, it may be rational to use an alternate drug with similar profile. Community-acquired antibiotic-resistant infections are likely to be met with and one must consider such a possibility based on local epidemiology.
 
DOSAGE, DURATION AND FREQUENCY OF ADMINISTRATION OF ANTIBIOTIC
 
Difficult Infections
Intracranial infection must be treated with higher dose for longer time due to variable concentration of drug achieved depending upon blood–brain barrier permeability. Thick wall, acid pH and presence of hydrolyzing enzymes necessitate higher dose of antibiotics. Higher dose for longer duration is required in endocarditis due to poor penetration at the site of infection. So the deep-seated infections, such as osteomyelitis, also demand long-term therapy.31
 
Host Factors
Dosage and/or frequency of administration may vary as per age, nutrition, immune status, renal and hepatic function. Frequency of antibiotic administration depends upon plasma half-life of a drug and generally, 4–5 times plasma half-life maintains adequate serum concentration throughout treatment period.
 
Route of Administration
Oral route is always preferred except in neonates and young infants and, of course, in serious infections. Intramuscular route is not ideal as it is painful and also has erratic absorption. Single dose of penicillin or ceftriaxone has been tried with success. Intravenous route is most ideal as it ensures achieving adequate concentration although, at times, not practical. Antibiotics that are used systemically should not be used topically.
 
ANTICIPATING INITIAL RESPONSE TO ANTIBIOTIC
Generally, it depends upon doubling time of organism—greater the doubling time, longer the response time. Partial control of fever may be the first response to antibiotic often accompanied with improvement in other symptoms and general wellbeing. For many common bacterial infections, initiation of response is observed within 2–3 days. It may take 4–5 days for initial response to antibiotic in typhoid fever, while in tuberculosis, initial response may be obtained within 2–4 weeks.
 
WHEN ANTIBIOTIC FAILS IN SUSPECTED BACTERIAL INFECTION?
Antibiotic rarely fails in routine office practice in treatment of community-acquired infection in a normal host. One should expect response to antibiotic within 3–4 days. If there is no response, it calls for reassessment.
Firstly, confirm whether it is an infection and, if so, a bacterial infection. This may be done by repeated physical examination supported by repeat laboratory tests. Choice of antibiotic and its route of administration may be a factor responsible for poor response. If bacterial infection and choice of antibiotic are reasonably confirmed, look for complications such as empyema in case of bacterial pneumonia or subdural collection in case of meningitis. At times, poor response may be due to iatrogenic factor such as catheter-related infection or nosocomial infection in a hospitalized setting. Only when all such factors are ruled out that one may consider drug resistance. It is ideal even at this stage to send blood culture and then change to best considered empirical antibiotic. However, if this change also fails, bacterial infection is ruled out and one must search for alternate diagnosis. It is not wise to persist with empirical antibiotic trial beyond one change.
 
WHEN NOT TO PRESCRIBE AN ANTIBIOTIC?
Non-bacterial infections obviously do not call for an antibiotic, and so also non-infective fevers. In routine office practice, it is possible to arrive at a provisional diagnosis by analyzing detailed history and focused physical examination. Typical viral infection starts with high fever at onset of illness that declines by day 3 or 4. Fever is rhythmic, rising every 4–6 hourly. As fever is partly controlled in 20–30 minutes after administration of paracetamol, child becomes active and does not look sick during inter-febrile period. Viral infection results in generalized affection of involved system. Thus, it may be accompanied with symptoms and physical signs of upper and lower respiratory tract involvement. There is often history of similar infection in other family members. Gastrointestinal symptoms in the form of vomiting and watery diarrhea denote involvement of upper (stomach) and lower GI tract (intestine) as a result of viral infection. Thus, viral infection is often disseminated, while bacterial infection is often localized.
Malaria presents with erratic pattern of fever that is essentially nonrhythmic. Child does not appear to be sick during interfebrile period.
Tuberculosis rarely presents as acute infection although acute onset of allergic pleural effusion may be a manifestation of tuberculosis in a healthy child. Non-infective conditions may present with fever wherein there is no localization during initial period. Disease evolves over time and at times may take even few months before being correctly labeled. Differentiation between acute bacterial infection and non-infective inflammatory disorder is, at times, difficult and in such a case, trial of antibiotic would fail to reveal correct diagnosis.
 
PRESENT SCENARIO OF IRRATIONAL ANTIBIOTIC USE
Antibiotics are considered to be the greatest discovery of twentieth century. In pre-antibiotic era, infectious diseases accounted for significant morbidity and mortality, and invasive procedures were fraught with risk of infection. All this changed with the use of antibiotics. But this miracle seems to be short-lived. Irresponsible and erratic use of these life-saving drugs has resulted in development of drug resistance in many organisms and death due to hospital-acquired infections is on the rise. It appears that our complacency is leading us into bigger problems in the present millennium.32
Various studies conducted in developed as well as developing countries during the last few years show that irrational drug use is a global phenomenon.
 
WHY DO DOCTORS OVERPRESCRIBE ANTIBIOTICS?
Uncertainty of diagnosis and lack of confidence are two major reasons for irrational use of antibiotics. Faulty training of medical students, lack of effective continued medical education and poor communication between doctors and patients have compounded the problem of irrational therapy. Many doctors succumb to peer pressure and parental pressure. Ineffective drug regulation and aggressive pharmaceutical marketing practices have contributed to increasing irrationality of drug prescriptions. “Mixed” infections with bacteria and ameba are not known to occur and this “mixing” is done by drug industry to sell two drugs where none may be indicated. Fear of legal suit makes doctors overreact to patient's need of drugs because of firm belief that error of commission is acceptable but not error of omission. Even, irrational drug prescription can be a bone of contention in courts, more so, if it results in side effects. It is the negligence that is punished and not mistakes, especially if they are within realm of expected competence and scientific limitations.
 
RATIONAL DRUG THERAPY: RATIONAL PRESCRIBER A PRIORITY!
Although rational drug therapy is a joint responsibility of policy makers, drug manufacturers, healthcare professionals as well as patients, doctors provide final decision of use of drugs. Hence, rational prescriber is a priority to success of rational drug therapy. Rationality should ensure safety at all costs and should try to confine to the limits of acceptable standards. Rationality may have a changing concept. Paracetamol is considered to be an antipyretic of choice but even ibuprofen or mefenamic acid is an acceptable alternative. Oral rehydration solutions have undergone modifications and have been the mainstay of treatment of diarrhea. However, it is well known that not all children suffering from diarrhea accept oral rehydration solution (ORS). It is now proved that those children who do not accept ORS lose much less electrolytes in stool. So rationality demands to hydrate a child suffering from diarrhea with suitable modification but within limits. Knowing that asthma is a chronic inflammatory disease, inhaled steroids have emerged frontline drug for its treatment. Thus, rational prescriber has to learn, unlearn and relearn to keep pace with changing concept.
 
HOW TO PREVENT MISUSE OF ANTIBIOTICS?
It is vital to arrive at provisional working diagnosis based on clinical analysis of detailed history and focused physical examination. If doctors learn to document provisional diagnosis, drug prescription is likely to be rational. Every doctor is expected to follow standard, national or organizational guidelines and document actions taken with justifications including instructions to parents or patients. Such documentation is a proof of honesty, transparency and responsibility on the part of the doctor. This alone increases confidence in rational therapy. Restricted hospital drug formulary would inculcate ideal therapeutic practice among doctors. Education has a role but may not ensure rational behavior of doctors. There is a need for group audit but best would be self-audit. Drug regulatory authority must ban irrational drugs. Drug controller in USA banned commonly used cold and cough remedies few years ago.
In view of misuse and overuse of antibiotics, council for appropriate and rational antibiotic therapy (CARAT) was formed in USA to guide rational antibiotic therapy.
In summary, rational drug therapy and, in particular rational antibiotic therapy is the need of the hour. Empirical antibiotic therapy has a place in routine practice, but only with rational approach. It includes assessing risk of waiting, clinically evaluating probable etiology of disease, supported by relevant laboratory tests, repeated observation to monitor progress, selecting appropriate empirical drug and reassessment in case of poor response. With indiscriminate antibiotic use, there has been increasing drug resistance and time has come to change this trend lest we are defeated by simple infections.
 
BIBLIOGRAPHY
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  1. Slama TG, Amin A, Brunton SA, et al. A clinician's guide to the appropriate and accurate use of antibiotics: the council for appropriate and rational antibiotic therapy (CARAT) criteria. Am J Med. 2005;118:1S–6S.