Index

A

Advisory boards, 12, 17–18, 284

Africa, 2, 3, 4–5, 32, 43, 56, 68, 217–218, 223, 225, 244, 260, 284

surveillance, vectors, 118, 127

Agency for International Development, 7, 44, 45, 47–48, 49, 50, 51, 157

Agriculture, 223, 259–261

irrigation and malaria, 218–219, 259, 261

migrant workers, 2, 4

plains malaria, 220

AIDS, 47, 52, 73, 74, 78, 82, 160

diagnostic tests and transfusions, transmission of, 13, 56, 60–61, 62, 164, 213

Amino acids, 96, 97, 153, 179

Aminoglycoside antibiotics, 156

Anemia, 13, 24, 61–62, 64, 65

Animal models

antimosquito vaccines, 195–196

cerebral malaria, 60

drug effects, 157–160, 161

vaccine actions, 173, 176, 178, 180, 181, 189, 190, 192, 194, 195

Anopheles, 4, 26, 27, 29, 40, 119–122, 124, 125, 136, 172, 222, 259, 260, 262, 263

An. arabiensis, 217, 263

An. claviger, 40

An. dirus, 218

An. farauti, 196

An. funestus, 217, 219

An. gambiae, 27, 28, 30, 34, 41, 124, 217, 259, 263

An. maculipennis, 125

An. stephensi, 27, 195, 219, 224, 263

Antibiotics, 147, 148, 156, 160

Antibodies, 81–82, 95, 128

antimosquito vaccines, 133

drug development, general, 147, 173–174, 178–179

immunoglobulin, 123, 179

monoclonal, 77, 82, 178–179, 188, 191–192, 193

tumor necrosis factor, 59, 61, 189



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MALARIA: Obstacles and Opportunities Index A Advisory boards, 12, 17–18, 284 Africa, 2, 3, 4–5, 32, 43, 56, 68, 217–218, 223, 225, 244, 260, 284 surveillance, vectors, 118, 127 Agency for International Development, 7, 44, 45, 47–48, 49, 50, 51, 157 Agriculture, 223, 259–261 irrigation and malaria, 218–219, 259, 261 migrant workers, 2, 4 plains malaria, 220 AIDS, 47, 52, 73, 74, 78, 82, 160 diagnostic tests and transfusions, transmission of, 13, 56, 60–61, 62, 164, 213 Amino acids, 96, 97, 153, 179 Aminoglycoside antibiotics, 156 Anemia, 13, 24, 61–62, 64, 65 Animal models antimosquito vaccines, 195–196 cerebral malaria, 60 drug effects, 157–160, 161 vaccine actions, 173, 176, 178, 180, 181, 189, 190, 192, 194, 195 Anopheles, 4, 26, 27, 29, 40, 119–122, 124, 125, 136, 172, 222, 259, 260, 262, 263 An. arabiensis, 217, 263 An. claviger, 40 An. dirus, 218 An. farauti, 196 An. funestus, 217, 219 An. gambiae, 27, 28, 30, 34, 41, 124, 217, 259, 263 An. maculipennis, 125 An. stephensi, 27, 195, 219, 224, 263 Antibiotics, 147, 148, 156, 160 Antibodies, 81–82, 95, 128 antimosquito vaccines, 133 drug development, general, 147, 173–174, 178–179 immunoglobulin, 123, 179 monoclonal, 77, 82, 178–179, 188, 191–192, 193 tumor necrosis factor, 59, 61, 189

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MALARIA: Obstacles and Opportunities vaccine development, 133, 173–174, 178–179, 182, 183–186, 188, 191–193, 195, 197 vector ingestion of human, 123 see also Immunoassays Antigens, 95, 99–100 erythrocyte surface, 188 immunoassays, 77–79, 82, 85, 86 liver, 170, 172, 177 neoantigens, 99–100 transmission-blocking vaccines, 194 vaccines, 170, 177–178, 180, 188–189, 191, 194 variation, 102–103 see also Cell-mediated immunity Antimalarial drugs, see Drugs, antimalarial Army Medical Research and Development Command, 49, 153 Artemisinin, 148, 155–156, 159, 162 Assays, 73, 77–78, 181, 124, 139 ELISA, 77–78, 80, 81, 127 immunoassays, general, 77–79, 82, 85, 86 in vitro techniques, 45, 66, 96, 109, 122, 138, 155, 158, 170, 173, 198, 229 radioimmunoassays, 78–79 vaccine development, 181 vector studies, 122, 126 Asymptomatic infections, 22, 74, 212–214, 234 Autologous red blood cell agglutination assay, 82 B B cells, 174, 177, 178 Bacillus thuringiensis israeliensis, 35 Bednets, 35, 130, 131, 132, 223, 228, 235–236 Behavioral factors, 8, 223–224, 226, 257, 264–265, 271–272 clothing, protective, 35 research, 13–14, 258, 271–274 see alsoCultural factors; Migration; Social factors; Travel and tourism Beta-lactam antibiotics, 156 Biochemistry, general, 90, 107, 163 see also Drugs; Vaccines Biological control agents, vectors, 35, 133–134, 229 Board for the Co-ordination of Malaria Studies, 157 BW566c, 160 C California, 3–4 Cell-mediated immunity, 174–182 passim, 186, 189, 193, 194 immunoglobulin, 123, 179 Centers for Disease Control, 48, 51, 157 Cerebral malaria, 13, 57–61, 23, 65, 265 Children, 4–5, 13, 47, 169, 184, 189, 213, 215, 218, 234 antimalarial drugs, 158, 184, 225 bednets, 228 endemics, 33, 146, 222–223 severe malaria, 58, 61, 62, 66–67, 145–146, 169, 189, 211, 220, 225, 244 China, 155 Chloramphenicol, 156 Chlorguanil, 153 Chloroquine, 3, 4, 5, 35, 45, 60, 64, 107–108, 129, 144, 147, 148, 150–151, 156, 157, 160–161, 267, 268, 269 Chlorproguanil, 153 Chlorpromazine, 161 Chronic complications, 27, 63, 145, 147, 222 Circumsporozoite protein (CS protein), 91, 175–181 Civil War, 39 Classification, see Taxonomy Climate, 28, 30, 218, 219, 222 see also Seasonal factors Clindamycin, 156 Clinical factors, 23–24, 57–64 pathogenesis, 13, 65 research, 65

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MALARIA: Obstacles and Opportunities see also Diagnosis; Symptoms Clinical immunity, 24, 108, 129, 132, 146, 172, 173, 213, 218 P. falciparum, 146, 213 research, 108, 129, 132 Clinical trials, 161–162, 170, 190–191, 198 Cloning, 100, 102, 103–104, 163 monoclonal antibodies, 77, 82, 178–179, 188, 191–192, 193 Clothing, protective, 35 Coastal zones, 220–221 Control strategies, general, 1–2, 6, 10–11, 15–20, 34–36, 284 biological agents, 35, 133–134, 229 community participation, 269–271, 273–274 cost-effectiveness, 131, 240–243, 244, 246, 247–252, 257–258 decentralization, programs, 216, 234 economic factors, general, 10, 237–253 epidemiology and, 212–214, 215–236 eradication, 41–45, 212, 232, 263, 274 funding, 8, 9, 10, 11, 13–14, 15, 44 historical perspectives, 41–45 larvicides, 35, 130, 131, 228 larvivorous fish, 35, 123, 131 local programs, 16–17, 216, 226, 232, 233, 234, 238, 240, 243–244, 245, 252, 257 program evaluation, 18, 233, 253, 269, 273–274 program planning, 216, 230–234, 257, 269, 273–274 research on, 12, 13–14, 15–20, 139–140 social and behavioral factors, 13–14, 257, 258, 264–271 vectors, 15, 119, 129–134, 140, 243, 244, 269–270 zooprophylaxis, 228 see also Drugs; Insecticides; Vaccines Convulsions, 60, 154 Coordination, see Management and managers; Organizational factors; Policy Costs and cost-effectiveness, 2, 18, 19, 237–243 control strategies, general, 131, 240–243, 244, 246, 247–252, 257–258 diagnostic tests, 73, 82 insecticides, 133, 244 larval control, 131 vaccines, 195 Cultural factors, 13–14, 223–224, 264–274 Cytoadherence, 98–99, 108 D DDT, 35, 41, 42, 44–45, 132–133, 259 Demographic factors, 214–215, 222–223, 259 migrant workers, 2, 4, 260, 262 migration, other, 2, 223, 260, 261–262, 264 population exposed, 32 see also Cultural factors; Epidemiology; Migration; Military personnel; Social factors Department of Defense, 11, 49–50, 52, 157–158 Army Medical Research and Development Command, 49, 153 Naval Medical Research Institute, 49–50 see also Walter Reed Army Institute of Research Desert fringe malaria, 219 Development projects, 226, 261, 281 Developmental biology, 107 Diagnosis, 3, 13, 16, 24–25, 56, 73–86, 214 costs, 73, 82 international programs, 158 via microscope, 75, 76, 158 national screening programs, 157 urine, diagnosis using, 158 see also Assays; Symptoms DNA, 79–81, 82, 86, 108–109, 126, 150, 151 vaccine development, 177, 180, 192, 194, 197

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MALARIA: Obstacles and Opportunities Doxycycline, 147, 156 Drugs, antimalarial, 10, 11, 15, 16, 34–35, 64–65, 120, 129, 140, 144–165, 280 administration, 144, 164 animal models, 157–160, 161 antibiotics, 147, 148, 156, 160 children and, 158, 184, 225 cultural beliefs, 268 drug resistance, 1, 3, 5, 10, 34–35, 45, 56, 60, 66, 103, 107–108, 144, 145, 147, 149, 150, 151, 152–153, 154, 155, 156, 157, 158, 160–161, 162–163, 226, 229, 235, 284 economic factors influencing development, 153, 158–159, 160, 195, 226 epidemiologic factors, 211, 225–226, 227, 229, 235 evaluation, 64–65 funding, 11, 45, 52 genetics, 103, 104, 148, 150, 151 guidelines, 17, 63, 146, 229, 244, 246, 272 historic perspectives, 35, 39, 148, 150, 154, 155, 156–158, 160 liver, effects on, 145, 148–149, 156 P. falciparum P. vivax, 35, 145, 146, 150, 152, 156, 161, 163–164 pregnant women, 153–154, 158, 244 private sector, 153, 158–159, 160, 171 research, 66–68, 140, 144, 155, 156–165, 171–172, 190 schizonticidal, general, 129, 149, 158, 162 side effects, 60, 145, 148, 149, 152, 154, 155, 159–160, 268 travelers, 3, 64, 65–66, 131, 172, 179, 181 see also Artemisinin; BW566c; Chloramphenicol; Chlorguanil; Chloroquine; Chlorproguanil; Chlorpromazine; Clindamycin; Doxycycline; Erythromycin; Floxacrine; Halofantrine; Hydroxynaphthoquinones; Mefloquine; Pamaquine; Primaquine; Proguanil; Pyrimethamine; Quinazoline; Quinine; Quinolines; Rifampicin; Sulfa drugs; Tetracyclines; WR238605 E Economic factors, 10, 237–253, 269, 283 control programs, general, 10, 237–253 drugs, 153, 158–159, 160, 195, 226 epidemiology and, 213, 223–225, 226, 242, 246–253, 264 eradication, 43 local programs, 238, 240, 243–244, 252 research, 238–242, 252–253 vaccine development, 171 see also Costs and cost-effectiveness; Foreign aid; Funding Education and training, 6, 20–21 diagnosis and treatment, 16, 17, 76–77, 78 evaluation of, 253, 272–273 local programs, general, 17, 229, 232 managers, 20, 21, 231–232, 252 parasite biology, 104–105 professional, general, 6, 20–21, 56, 229, 231–232, 282, 270–271 public, 56, 224, 226, 229, 244, 253, 264–269, 272–273, 282 treatment guidelines, 17, 63, 146, 229, 244, 246, 272 vector biology, 134–135 Emigration, see Migrant workers; Migration Endemicity, 33–34, 120, 127, 128, 131, 132, 146, 213, 221, 242, 253, 267, 279 AIDS and, 60–61

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MALARIA: Obstacles and Opportunities children and, 33, 146, 222–223 clinical immunity, 24, 108, 129, 132, 146, 172, 173, 213, 218 vaccines, 181 Entomological inoculation rate, 126, 128, 129, 136, 137 Environmental issues, 30 biological agents, 133–134 insecticides, 44–45, 118, 132–133 Enzyme-linked immunosorbent assays (ELISA), 77–78, 80, 81, 127 Epidemics, 10, 33, 219, 285 Epidemiology, 30–34, 118, 211–236 Centers for Disease Control, 48, 51 control strategies and, 212–214, 215–236 diagnostic tests and, 84, 86 drugs, 211, 225–226, 227, 229, 235 economics and, 213, 223–225, 226, 242, 246–253, 264 entomological inoculation rate, 126, 128, 129, 136, 137 geographical factors, 22, 30–32, 122, 124, 125, 127, 213, 217–222, 238 historical perspectives, 212, 215, 232, 259 immunology and, 24, 32, 66, 212, 213, 222–223, 234 infection versus disease, 22, 74, 212–214, 234 microepidemiology, 135–136, 243–244 parasites, general, 221–222 P. falciparum, 213, 221, 222, 260 research, 135, 234–236, 247 severe malaria, 211, 219, 234 surveillance, 9–10, 118, 67–68, 127–128, 136–137, 229, 232–233, 282, 285 vaccines, 211, 235 vectors and, 123, 124–125, 129–134, 217, 219, 222, 227–228 see also Endemicity; Morbidity and mortality; Paradigm approach Erythrocytes anemia, 13, 24, 61–62, 64, 65 cytoadherence, 98–99, 108 parasite biology, general, 92–100 passim, 102, 106, vaccines, effects, 170, 171–172, 173, 175–177, 182–192 passim see also Hemoglobin Erythromycin, 156 Europe, 42, 46, 125 Evaluation, 19 bednets, 228 diagnostic tests, 76, 83–84 drugs, 64–65 education programs, 253, 272–273 of funding methods, 46 health workers, 270–271 outcome measures, 246 program-level, 18, 233, 253, 269, 273–274 research proposals, 9 vaccines, 129, 170 vector control, 140 see also Clinical trials; Costs and cost-effectiveness; Field studies; Research F Federal government, 43, 47–53, 157, 159, 160, 240 see also Agency for International Development; Centers for Disease Control; Department of Defense; National Institute of Allergy and Infectious Diseases Feeding behavior mosquitoes, 28–29 parasites, 94–95, 105 Fever, 25, 27, 38, 266 Field studies, 6, 9 bednets, 132 parasite transmission, 122, 125–126 vaccines, 128–129, 137, 140 vectors, 120, 122, 125–126, 128–129, 135–137, 138–139, 140 Fish, larvivorous, 35, 123, 131 Floxacrine, 161 Food and Drug Administration, 157, 159, 160

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MALARIA: Obstacles and Opportunities Foreign aid, 5, 8 development projects, 226, 261, 281 surveillance, 10 World Bank, 9, 158 see also Agency for International Development Foreign countries, general control strategies, 1–2, 6 incidence, 1, 2 political instability, 45 Forest malaria, 218, 220, 223 Funding, 7–21 passim, antimalarial drugs, 11, 45 control strategies, 8, 9, 10, 11, 13–14, 15, 44 drug development, 11, 45, 52 eradication, 43 federal, 47–53 see also Foreign aid G Gametocytes, 26, 27, 92–94, 121, 122, 137, 140, 145, 148, 149, 193, 227 Genetics, 24, 100–106 antimalarial drugs, 103, 104, 148, 150, 151 cloning, 100, 102, 103–104, 163 immune response, 32, 150, 180–181, 191, 194–195 monoclonal antibodies, 77, 82, 178–179, 188, 191–192, 193 mutation, 101–102, 103 parasites, 100–106, 109, 163 probe assays, 77, 79–81, 82, 85, 86 research, 107–109 vectors, 118, 121, 126, 133, 134, 138, 139 see also DNA; RNA Geographic factors, 30 access to health care, distance, 223, 283 coastal zones, 220–221 desert fringes, 219 drug sensitivities, 56 epidemiology, 22, 30–32, 122, 124, 125, 127, 213, 217–222, 238 forests, 218, 220, 223 highland fringes, 219 plains, 220 P. falciparum, 32, 124, 260 P. malariae, 32 P. vivax, 30, 32, 124, 220, 221–222 savannah lands, 217–218, 220, 223 urban areas, 119, 131, 219–220, 250–251, 257, 262–264 vectors, 122, 124, 125, 127, 136–137, 259 H Halofantrine, 148, 154–155, 156 Hemoglobin, 94–95, 96 anemia, 13, 24, 61–62, 64, 65 Hepatitis, 73, 74, 179, 213 Highland fringe malaria, 219 Historic perspectives, 1, 3, 7, 9, 37–53 agriculture and malaria, 259, 260 Civil War, 39 control strategies, drugs, 35, 39, 148, 150, 154, 155, 156–158, 160 epidemiology, 212, 215, 232, 259 eradication era, 41–45, 212, 232, 263, 274 social factors, 258, 259, 260, 263 United States, 38–39, 43, 47–53 urban areas, 263 vaccines, 172–173 World War II, 40, 41, 148, 150, 154, 156–157 Health care, see Treatment Health care personnel education, diagnosis and treatment, 16, 17, 76–77, 78 education, general, 6, 20–21, 56, 229, 231–232, 282, 270–271 education, parasite biology, 104–105 education, vector biology, 134–135 treatment guidelines, 17, 63, 146, 229, 244, 246, 272 Holoendemicity, 33 Host-parasite interactions, 28–29, 91–94, 98–100, 144

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MALARIA: Obstacles and Opportunities blood-stage, 92–98, 106, 153, 156, 170 see also Merozoites; Schizogony; Sporogony Housing, 131, 223–224, 262 Hydroxynaphthoquinones, 160 Hyperendemicity, 33–34 Hypoendemicity, 33, 34 Hypoglycemia, 59, 60, 61, 149 I Immigration, see Migration Immunoassays, 77–78, 126, 127–128, 139 antigens and, 77–79, 82, 85, 86 ELISA, 77–78, 80, 81, 127 radioimmunoassays, 78–79 Immunoglobulin, 123, 179 Immunology, 3, 24, 64, 123–124, 196–197 cell-mediated immunity, 174–182 passim, 186, 189, 193, 194 endemicity and immunity, 24, 108, 129, 132, 146, 172, 173, 213, 218 epidemiologic factors, 24, 32, 66, 212, 213, 222–223, 234 genetics of, 32, 150, 180–181, 191, 194–195 host defense evasions, 98–100 interferon, 174–175, 189 irradiated sporozoites, 6, 45, 105, 160, 173, 175, 196, 197 migration and, 262 research, 8, 14–15, 66, 106, 196–198 vector factors, 6, 45, 105, 123–124, 126 see also Antibodies; Antigens; Assays; Vaccines In vitro techniques, 45, 66, 96, 109, 122, 138, 155, 158, 170, 173, 198, 229 Indian National Malaria Eradication Program, 263 Information, see Education and training Insecticides, 16, 35, 130–131, 132, 227, 285 Africa, use in, 3 bednets, impregnated with, 35, 130, 131, 132, 223, 228, 235–236 cost-effectiveness, 133, 244 DDT, 35, 41, 42, 44–45, 132–133, 259 environmental issues, 44–45, 118, 132–133 larvicides, 35, 130, 131, 228 resistance to, 1, 42, 132, 257–258, 259 Insect repellents, 35, 131 Institute of Medicine, 6–7, 216, 283 Interferon, 174–175, 189 International Congress on Primary Health Care, 44 International perspectives, 1, 41–42, 44, 46–47 multinational businesses, 10 United Nations, 9, 41, 42, 44, 45, 158, 271 United Nations Development Program/World Bank/World Health Organization Special Programme for Research and Training in Tropical Diseases 9, 45, 46, 158, 171 World Bank, 9, 158 see also Foreign countries; World Health Organization Irradiation, 6, 45, 105, 170, 173, 175, 196, 197 Irrigation systems, 218–219, 259, 261 K Karyotypes, 101 Kidneys, 23, 63 L Laboratory studies, 137–139 in vitro techniques, 45, 66, 96, 109, 122, 138, 155, 158, 170, 173, 198, 229 P. falciparum culturing, 45, 79, 81, 122, 158, 170, 198, 229 P. vivax culturing, 81, 93, 163–164, 198

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MALARIA: Obstacles and Opportunities vectors, 120, 137–139 see also Assays Larvae, 35, 119, 228 ecology of, 123, 124, 125, 130, 263 fish, larvivorous, 35, 123, 131 larvicides, 35, 130, 131, 228 Legal issues, 262 Life cycles of mosquitoes, 27–28, 34, 40, 42, 123; see also Larvae of P. falciparum, 91–99 passim, 121, 122, 182, 183 of parasites, 25–27, 39–40, 90–94, 105–108, 119, 120–121, 122, 171, 193 see also Merozoites; Schizogony; Sporogony Lipids, 98, 189 Liver, 26, 91–92, 105–106 antigens, 170, 172, 177 drug effects, 145, 148–149, 156 hepatitis, 73, 74, 179, 213 vaccines and, 171–172, 174, 176, 177, 197 Local programs and factors control, 16–17, 216, 226, 232, 233, 234, 238, 240, 243–244, 245, 252, 257 community participation, 269–271, 273–274 development projects, 226 drug sensitivities, 56 economics, 238, 240, 243–244, 252 education and training, 17, 229, 232 microepidemiology, 135–136, 243–244 operational research, 232 vector populations, 119, 129 Logistics, 233, 268–269 M Macrogametocyte, 26, 120 Macrophages, 189 Management and managers, 19, 231, 233, 244, 245 training of, 20, 21, 231–232, 252 Mathematical models, 42 Mefloquine, 147, 148, 150, 153–154, 156, 158 Merozoites, 26–27, 61, 91, 92–93, 106 vaccines, 171–172, 184–185, 186–188, 191–192 Mesoendemicity, 33, 34 Microgametocyte, 26, 120 Microscopy, 75, 76, 158 Migrant workers, 2, 4, 260, 262 Migration, 2, 223, 260, 261–262, 264 Military personnel, 8, 39, 40, 49–50, 148, 156–157, 223, 227 Civil War, 39 Vietnam, 40, 157 World War II, 40, 41, 148, 150, 154, 156–157 see also Department of Defense Mitochondria, 97–98, 107, 160 Models, 42 see also Paradigm approach Molecular biology, see Genetic Monoclonal antibodies, 77, 82, 178–179, 188, 191–192, 193 Monocytes, 174 Morbidity and mortality, 56, 132, 214–215, 229, 238, 247 Mosquitoes, 27–29, 93–94, 118–140, 280–281 antibodies, human, ingestion by, 133 assays, 122, 126 biological control agents, 35, 133–134, 229 community control programs, 16 control, general, 15, 119, 129–134, 140, 243, 244, 269–270 demographic factors, 119 education on, 134–135 epidemiology and, 123, 124–125, 129–134, 217, 219, 222, 227–228 feeding behavior, 28–29 field studies, 120, 122, 125–126, 128–129, 135–137, 138–139, 140 genetics, 118, 121, 126, 133, 134, 138, 139 geographic distribution, 122, 124, 125, 127, 136–137, 259

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MALARIA: Obstacles and Opportunities immunological factors, 6, 45, 105, 123–124, 126 insect repellents, 35, 131 insecticide resistance, 1, 42, 132, 257–259 lab studies, 120, 137–139 life cycle, 27–28, 34, 40, 42, 123; see also Larvae local factors, 119, 129 parasites, interactions with, 93–94, 120–129, 137–138 personal protection from, 16, 227; see also Bednets; Clothing primary versus secondary vectors, 124 research on, 8, 15, 120, 135–140 taxonomy, 125 temperature factors, 28, 30, 105, 124 urban areas, 263 vaccines against, 118, 133, 137, 139, 169, 172, 195–196 vectorial capacity, 126–127 WHO programs, 126, 132–133 see also Anopheles; Insecticides; Larvae N National Institute of Allergy and Infectious Diseases, 7, 50, 52, 53 National Institutes of Health, 7, 9, 50, 52, 157 National Research Council, 134, 157 Naval Medical Research Institute, 49–50 Neoantigens, 99–100 North America, malaria in, 38–39 see also United States O Operational research, 20, 232, 233, 243–244, 259 Organizational factors, 243, 268–269 advisory boards, 12, 17–18, 284 decentralization, control programs, 216, 234 logistics, 233, 268–269 policy, general, 231, 237, 244–246, 252 program evaluation, 18, 233, 269, 273–274 program planning, 216, 230–234, 257, 269, 273–274 research coordination, 11–12 see also Management and managers P Pamaquine, 156 Pan American Sanitary Commission, 42 Paradigm approach, 18–19, 216–230, 235, 247, 250–252, 279–282, 285–286 Parasites, causing malaria, 90–109, 280 education on, 104–105 epidemiology and, 221–222 erythrocytes, general, 92–100 passim, 102, 106 feeding behavior, 94–95, 105 field studies of transmission, 122, 125–126 genetics, 100–106, 109, 163 life cycle, 25–27, 39–40, 90–94, 105–108, 119, 120–121, 122, 171, 193; see also Merozoites; Schizogony; Sporogony research on, 8, 104–109 vectors, interactions with, 93–94, 120–129, 137–138 see also Host-parasite interactions; and specific parasites Pathogenesis, 13, 65, 189 Peace Corps, 67–68 Penfluridol, 150 Pesticides, see Insecticides Phenothiazines, 161 Plains malaria, 220 Plasmodium cynomolgi, 180 Plasmodium falciparum, 1, 5, 22–27, 40, 65 antimosquito vaccines, 133 clinical immunity, 146, 213 culturing of, 45, 79, 81, 122, 158, 170, 198, 229

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MALARIA: Obstacles and Opportunities drug-resistance, 35, 45, 103, 147–148, 149, 150, 151, 154, 156, 163, 229 drugs, effective, 152, 153–155, 158, 161, 162–163, 229 epidemiology, 213, 221, 222, 260 genetics, 101–104, 109 geographic distribution, 32, 124, 260 life cycle, 91–99 passim, 179, 179, 179, 179 severe malaria, 23, 57–59, 66–67, 144, 182, 183, 213, 221, 222 vaccines, 133, 175, 176, 177, 178, 180, 181, 182, 186–194 passim 191 Plasmodium knowlesi, 152, 180 Plasmodium malariae, 22, 63, 121, 146 geographic distribution, 32 recurrence, 27 Plasmodium ovale, 22, 27, 145, 146 Plasmodium vivax, 1, 22, 27, 40, 95, 121 culturing, 81, 93, 163–164, 198 drug-resistant strains, 35, 150, 152, 161, 164 drugs, effective, 145, 146, 156, 161, 163–164 geographic distribution, 30, 32, 124, 220, 221–222 vaccines, 175, 178–179, 187–188, 190, 194, 195 Pneumocystis carinii, 160 Policy, 231, 237, 244–246, 252 advisory boards, 12, 17–18, 284 Polymerase chain reaction method, 80–81, 156 Population factors, see Cultural factors; Demographic factors; Migration; Social factors Pregnancy, 4, 13, 24, 60, 62, 64, 67, 211, 213, 234, 267 antimalarial drugs, 153–154, 158, 244 Primaquine, 147, 148–149, 157, 160 Private sector, 46 drug companies, 153, 158–159, 160, 171 health care, 225, 246, 253 multinational businesses, 10 Problem-solving, see Operational research Proguanil, 147, 153, 157 Projections, 57, 73, 90, 118, 144, 169, 211, 237, 257 Proteins, 91, 101–104, 109, 162, 163 immunoglobulin, 123, 179 interferon, 174–175, 189 vaccine development, 172, 175–179, 181–182, 185–189 passim, 191 Pulmonary edema, 62 Pyrimethamine, 151–153, 154, 157 Q Quantitative buffy coat technique, 76 Quinazoline, 161 Quinine, 39, 60, 147, 148, 149–150, 154 Quinoline drugs, 107, 105, 150, 159–160, 162–163 see also specific drugs R Radioimmunoassays, 78–79, 158 Rainfall, 218 Red blood cells, see Erythrocytes Relapse, see Chronic complications Research, 8, 12–15, 65–68, 284 antimalarial drugs, 66–68, 140, 144, 155, 156–165, 171–172, 190 clinical immunity, 108, 129, 132 clinical trials, 161–162, 170, 190–191, 198 control strategies, 12, 13–14, 15–20, 139–140 coordination of, 11–12 diagnosis, 77, 76–82, 84–86 economics, 238–242, 252–253 epidemiology, 135, 234–236, 247 eradication, 43 field, 6, 9 funding, 7–21 passim, 44, 45, 46, 53 genetics, 107–109 immunology, 8, 14–15, 66, 106, 196–198 operational, 20, 232, 233, 243–244, 259 parasites, 8, 104–109

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MALARIA: Obstacles and Opportunities pathogenesis, 13, 65 social and behavioral factors, 13–14, 258, 271–274 treatment, 65–66 vaccines, 6, 8, 11, 14–15, 170, 196–198 vectors, 8, 15, 120, 135–140 see also Evaluation; Field studies; Laboratory studies Rifampicin, 156 RNA, 80, 104, 156 S Savannah lands, 217–218, 220, 223 Schizogony, 24–25, 26–27, 61, 93, 188 drugs, 129, 149, 158, 162 see also specific schizonticidal drugs Seashore malaria, 220–221 Seasonal factors, 129, 132, 137, 217–218, 220, 222 Secondary metabolism, 164–165 Severe and complicated malaria, 13, 16, 23, 57–63, 64, 65, 144, 211, 219, 234 cerebral malaria, 13, 57–61, 23, 65, 265 chronic complications, 27, 63, 145, 147, 222 P. falciparum, 23, 57–59, 66–67, 144, 182, 183, 213, 221, 222 vaccines against, 169, 189 see also Children; Pregnancy Skin patch administration, drugs, 164 Sleeping habits, 224 bednets, 35, 130, 131, 132, 223, 228, 235–236 Social factors, 13–14, 223–224, 240, 242, 257–274, 280 community participation, 269–271, 273–274 historical perspectives, 258, 259, 260, 263 housing, 131, 223–224, 262 political instability, 45 professional training about, 20 research, 13–14, 258, 271–274 see also Migration Spleen, 33, 61–62, 63 Sporogony, 26, 30, 91, 94, 105, 106, 120–126 , 128, 138, 176–177 circumsporozoite protein, 175–176 irradiation, 6, 45, 105, 170, 173, 175, 196, 197 vaccine development, 133, 171, 172–182, 190, 196, 197 Stevens-Johnson syndrome, 152 Sulfa drugs, 152, 154 Surveillance, 9–10, 67–68, 118, 127–128, 136–137, 229, 232–233, 282, 285 Switzerland, 4 Symptoms, 23, 74, 267 asymptomatic infections, 22, 74, 212–214, 234 fever, 25, 27, 38, 266 convulsions, 60, 154 T T cells, 174, 175, 176, 177, 179–181, 182, 189, 193, 194 Tanzania, 5 Taxonomy entomology, 125 nosological fusion, 267–268 paradigm approach, 18–19, 216–230, 235, 247, 250–252, 279–282, 285–286 Temperature factors, 28, 30, 105, 120–121, 124 Temporal factors, 242–243 infection progression, 66–67, 120–121 seasonality, 129, 132, 137, 217–218, 220, 222 vaccines, duration of protection, 181–182 see also Seasonal factors Tetracyclines, 147, 148, 156 Training, see Education and training Transportation, 233 access to health care, distance, 223, 283

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MALARIA: Obstacles and Opportunities Travel and tourism, 2–3, 4, 5, 8, 131, 223 antimalarial drugs, 3, 64, 65–66, 131, 172, 179, 181 information on, 56 Treatment, 6, 16, 65–66, 235, 257 access to health care, distance, 223, 283 costs, versus control strategies, 244 guidelines, 17, 63, 146, 229, 244, 246, 272 see alsoDrugs; Health care personnel Trophozoites, 95 Tumor necrosis factor, 59, 61, 189 U Uncomplicated malaria, general, 63–64 United Kingdom, 153 United Nations, 9, 41, 42, 44, 45, 158, 271 United Nations Development Progam/World Bank/World Health Organization Special Programme for Research and Training in Tropical Diseases 9, 45, 46, 168, 271 United States DDT, 44–45 historical perspectives, 38–39, 43, 47–53 see alsoFederal government Urban areas, 119, 131, 219–220, 250–251, 257, 262–264 Urine, diagnosis using, 158 V Vaccines animal models, 173, 176, 178, 180, 181, 189, 190, 192, 194, 195–196 antibodies, 133, 173–174, 178–179, 182, 183–186, 188, 191–193, 195, 197 antigens, 170, 177–178, 180, 188–189, 191, 194 antimalarial, 6, 8, 11, 14–15, 36, 45, 52, 128–129, 156, 169–195, 196–198 antimosquito, 118, 133, 137, 139, 169, 172, 195–196 assays, 181 blood-stage, general, 128, 182–192 children, 169, 184, 189 costs, 195 DNA, 177, 180, 192, 194, 197 duration of protection, 181–182 economics, 171 endemicity and, 181 entomological components, 128–129, 192–195 epidemiological factors, 211, 235 erythrocytes, 170, 171–172, 173, 175–177, 182–192 passim evaluation, general, 129, 170 field studies, 128–129, 137, 140 historical perspective, 172–173 liver, effects on, 171–172, 174, 176, 177, 197 merzoites, 171–172, 184–185, 186–188, 191–192 P. falciparum, 133, 175, 176, 177, 178, 180, 181, 182, 186–194 passim P. vivax, 175, 178–179, 187–188, 190, 194, 195 proteins, 172, 175–179, 181–182, 185–189 passim, 191 research, general, 8, 14–15, 66, 106, 196–198 severe malaria, 169, 189 side effects, 169 sporozoites, 133, 171, 172–182, 190, 196, 197 transmission-blocking, 192–195 Vectorial capacity, 126–127 Vectors, see Mosquitoes Vietnam, 40, 157 W Walter Reed Army Institute of Research, 11, 49–50, 157–158, 159 World Bank, 9, 158

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MALARIA: Obstacles and Opportunities World Health Organization, 9, 41, 42, 43–44, 45, 46, 48, 51, 63, 271 antimalarial drugs, 153, 154, 155, 157, 158, 159 epidemiology, 212, 214, 215–216, 285 vector biology and control, 126, 132–133 World War II, 40, 41, 148, 150, 154, 156–157 WR Z Zooprophylaxis, 228

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MALARIA: Obstacles and Opportunities